psychoactive side effects: Topics by Science.gov

Sample records for psychoactive side effects

The Nootropic Concept and Dyslexia.

ERIC Educational Resources Information Center

Wilsher, Colin R.

1986-01-01

Studies with Nootropic psychoactive drugs (such as Piracetam) suggest that Piracetam lacks significant side effects; promotes memory and learning; and improves the reading ability of dyslexics, possibly by directly affecting the left-brain hemisphere. Results are contrasted with studies showing the lack of effectiveness of intensive teaching.…
DEVELOPING A VACCINE AGAINST MULTIPLE PSYCHOACTIVE TARGETS: A CASE STUDY OF HEROIN

PubMed Central

Stowe, G. Neil; Schlosburg, Joel E.; Vendruscolo, Leandro F.; Edwards, Scott; Misra, Kaushik K.; Schulteis, Gery; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.

2012-01-01

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin’s effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment. PMID:22229311
[The lived experience of the women with schizophrenia taking antipsychotic medication].

PubMed

Song, Eun-Ju

2011-06-01

This study was done to identify some natural meaning through the dosage experience of psychoactive drugs in women patients with schizophrenia. The Hermeneutic phenomenology written by van Manen was used. The period for data collection was from November 2009 to January 2010. This study took place in mental health hospitals and mental health centers in two cities in North Jeolla Province. Nine patients with schizophrenia participated. Data collection was done through individual in-depth interview. The seven natural subjects demonstrated by participants from this study were 'Pills forcibly taken like veiled threats', 'A terrible side effect, a side effect rooted slowly', 'Shame which cannot be hidden as a woman', 'A bad medicine took away from motherhood', 'The fate of a wife who can't be equal', 'A struggle for the complete recovery without promise', and 'Participants want the future without medicine'. The results of this study indicate that the urgent need to develop a safe and believable psychoactive drug for woman patients considering the time of menstruation, pregnancy, childbirth, and child raising.
Health and Social Problems Associated with Recent Novel Psychoactive Substance (NPS) Use Amongst Marginalised, Nightlife and Online Users in Six European Countries.

PubMed

Van Hout, Marie Claire; Benschop, Annemieke; Bujalski, Michal; Dąbrowska, Katarzyna; Demetrovics, Zsolt; Felvinczi, Katalin; Hearne, Evelyn; Henriques, Susana; Kaló, Zsuzsa; Kamphausen, Gerrit; Korf, Dirk; Silva, Joana Paula; Wieczorek, Łukasz; Werse, Bernd

2018-01-01

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland ( n = 3023). Some respondents were unable to categorise NPS they had used. Use of ' herbal blends ' and ' synthetic cannabinoids obtained pure ' was most reported in Germany, Poland and Hungary, and use of ' branded stimulants ' and ' stimulants/empathogens/nootropics obtained pure ' was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted.
Cannabidiol as potential anticancer drug

PubMed Central

Massi, Paola; Solinas, Marta; Cinquina, Valentina; Parolaro, Daniela

2013-01-01

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ9-THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ9-THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. PMID:22506672
Effects and risks associated with novel psychoactive substances: mislabeling and sale as bath salts, spice, and research chemicals.

PubMed

Hohmann, Nicolas; Mikus, Gerd; Czock, David

2014-02-28

The number of newly reported psychoactive substances in Europe is now higher than ever. In order to evade legal restrictions, old and novel psychoactive substances from medical research and their derivatives are commonly mislabeled as "not for human consumption" and offered for sale on the Internet and elsewhere. Such substances are widely taken by young people as "club drugs." Their consumption must be considered in the differential diagnosis of psychiatric, neurological, cardiovascular, or metabolic disturbances of unclear origin in a young patient. Selective review of pertinent literature retrieved by a PubMed search, including publications by government-sponsored organizations. From 2010 to 2012, 163 substances were reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), mostly either synthetic cannabinoids (39.3%) or synthetic cathinones (16.6%). Synthetic cannabinoids alter mood and perception; intoxications cause agitation, tachy cardia, and arterial hypertension. Synthetic cathinones are hallucinogenic stimulants with predominantly cardiovascular and psychiatric side effects. Severe intoxications cause serotonin syndrome and potentially fatal rhabdomyolysis. Substances in either of these classes often escape detection in screening tests. Young persons who present with agitation and cardiovascular and/or psychiatric manifestations of unclear origin and whose drug screening tests are negative may be suffering from an intoxication with a novel psychoactive substance. Physicians should know the classes of such substances and their effects. Targeted toxicological analysis can be carried out in a toxicology laboratory or a facility for forensic medicine.
Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect

PubMed Central

Solinas, Marta; Massi, Paola; Cinquina, Valentina; Valenti, Marta; Bolognini, Daniele; Gariboldi, Marzia; Monti, Elena; Rubino, Tiziana; Parolaro, Daniela

2013-01-01

In the present study, we found that CBD inhibited U87-MG and T98G cell proliferation and invasiveness in vitro and caused a decrease in the expression of a set of proteins specifically involved in growth, invasion and angiogenesis. In addition, CBD treatment caused a dose-related down-regulation of ERK and Akt prosurvival signaling pathways in U87-MG and T98G cells and decreased hypoxia inducible factor HIF-1α expression in U87-MG cells. Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways. As CBD is a non-psychoactive phytocannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anti-cancer drug in the management of gliomas. PMID:24204703
Predicting the activity and toxicity of new psychoactive substances: a pharmaceutical industry perspective.

PubMed

Leach, Andrew G

2014-01-01

Predicting the effect that new compounds might have when administered to human beings is a common desire shared by researchers in the pharmaceutical industry and those interested in psychoactive compounds (illicit or otherwise). The experience of the pharmaceutical industry is that making such predictions at a usefully accurate level is not only difficult but that even when billions of dollars are spent to ensure that only compounds likely to have a desired effect without unacceptable side-effects are dosed to humans in clinical trials, they fail in more than 90% of cases. A range of experimental and computational techniques is used and they are placed in their context in this paper. The particular roles played by computational techniques and their limitations are highlighted; these techniques are used primarily to reduce the number of experiments that must be performed but cannot replace those experiments. Copyright © 2013 John Wiley & Sons, Ltd.
Wide-range screening of psychoactive substances by FIA-HRMS: identification strategies.

PubMed

Alechaga, Élida; Moyano, Encarnación; Galceran, Maria Teresa

2015-06-01

Recreational drugs (illicit drugs, human and veterinary medicines, legal highs, etc.) often contain lacing agents and adulterants which are not related to the main active ingredient. Serious side effects and even the death of the consumer have been related to the consumption of mixtures of psychoactive substances and/or adulterants, so it is important to know the actual composition of recreational drugs. In this work, a method based on flow injection analysis (FIA) coupled with high-resolution mass spectrometry (HRMS) is proposed for the fast identification of psychoactive substances in recreational drugs and legal highs. The FIA and HRMS working conditions were optimized in order to detect a wide range of psychoactive compounds. As most of the psychoactive substances are acid-base compounds, methanol-0.1 % aqueous formic acid (1:1 v/v) as a carrier solvent and electrospray in both positive ion mode and negative ion mode were used. Two data acquisition modes, full scan at high mass resolution (HRMS) and data-dependent tandem mass spectrometry (ddMS/HRMS) with a quadrupole-Orbitrap mass analyzer were used, resulting in sufficient selectivity for identification of the components of the samples. A custom-made database containing over 450 substances, including psychoactive compounds and common adulterants, was built to perform a high-throughput target and suspect screening. Moreover, online accurate mass databases and mass fragmenter software were used to identify unknowns. Some examples, selected among the analyzed samples of recreational drugs and legal highs using the FIA-HRMS(ddMS/HRMS) method developed, are discussed to illustrate the screening strategy used in this study. The results showed that many of the analyzed samples were adulterated, and in some cases the sample composition did not match that of the supposed marketed substance.
The psychoactive effects of psychiatric medication: the elephant in the room.

PubMed

Moncrieff, Joanna; Cohen, David; Porter, Sally

2013-01-01

The psychoactive effects of psychiatric medications have been obscured by the presumption that these medications have disease-specific actions. Exploiting the parallels with the psychoactive effects and uses of recreational substances helps to highlight the psychoactive properties of psychiatric medications and their impact on people with psychiatric problems. We discuss how psychoactive effects produced by different drugs prescribed in psychiatric practice might modify various disturbing and distressing symptoms, and we also consider the costs of these psychoactive effects on the mental well-being of the user. We examine the issue of dependence, and the need for support for people wishing to withdraw from psychiatric medication. We consider how the reality of psychoactive effects undermines the idea that psychiatric drugs work by targeting underlying disease processes, since psychoactive effects can themselves directly modify mental and behavioral symptoms and thus affect the results of placebo-controlled trials. These effects and their impact also raise questions about the validity and importance of modern diagnosis systems. Extensive research is needed to clarify the range of acute and longer-term mental, behavioral, and physical effects induced by psychiatric drugs, both during and after consumption and withdrawal, to enable users and prescribers to exploit their psychoactive effects judiciously in a safe and more informed manner.
The Psychoactive Effects of Psychiatric Medication: The Elephant in the Room

PubMed Central

Cohen, David; Porter, Sally

2013-01-01

The psychoactive effects of psychiatric medications have been obscured by the presumption that these medications have disease-specific actions. Exploiting the parallels with the psychoactive effects and uses of recreational substances helps to highlight the psychoactive properties of psychiatric medications and their impact on people with psychiatric problems. We discuss how psychoactive effects produced by different drugs prescribed in psychiatric practice might modify various disturbing and distressing symptoms, and we also consider the costs of these psychoactive effects on the mental well-being of the user. We examine the issue of dependence, and the need for support for people wishing to withdraw from psychiatric medication. We consider how the reality of psychoactive effects undermines the idea that psychiatric drugs work by targeting underlying disease processes, since psychoactive effects can themselves directly modify mental and behavioral symptoms and thus affect the results of placebo-controlled trials. These effects and their impact also raise questions about the validity and importance of modern diagnosis systems. Extensive research is needed to clarify the range of acute and longer-term mental, behavioral, and physical effects induced by psychiatric drugs, both during and after consumption and withdrawal, to enable users and prescribers to exploit their psychoactive effects judiciously in a safe and more informed manner. PMID:24592667
Life-threatening complications of ibogaine: three case reports.

PubMed

Paling, F P; Andrews, L M; Valk, G D; Blom, H J

2012-11-01

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.
The ethnobotany of psychoactive plant use: a phylogenetic perspective

PubMed Central

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders. PMID:27761334
The ethnobotany of psychoactive plant use: a phylogenetic perspective.

PubMed

Alrashedy, Nashmiah Aid; Molina, Jeanmaire

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders.
Novel psychoactive substances: overdose of 3-fluorophenmetrazine (3-FPM) and etizolam in a 33-year-old man.

PubMed

Benesch, Matthew G K; Iqbal, Sahar J

2018-06-08

Though illegal in the UK, in many countries novel psychoactive substances are quasi-legal synthetic compounds that are widely available online under the guise of research chemicals. These substances are relatively cheap and are often undetectable in standard drug screens. Nearly 200 such compounds are introduced yearly, and little is usually known about their metabolism or physiological effects. Consequently, managing patients in overdose situations on largely unknown substances usually involves supportive care, however anticipating and managing atypical side effects are challenging in the absence of knowledge of these compounds. In this report, we discuss our encounter with a 33-year-old unconscious man presenting with coingestion of a novel stimulant 3-fluorophenmetrazine with a rarely used benzodiazepine etizolam. This patient developed seizure-like activity and delayed widespread T-wave inversions, both of which ultimately resolved without sequelae. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

2016-01-01

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272
Expanding Course Goals beyond Disciplinary Boundaries: Physiology Education in an Undergraduate Course on Psychoactive Drugs

ERIC Educational Resources Information Center

Near, Joseph A.; Martin, Bruce J.

2007-01-01

The topic of psychoactive drugs is one of inherent interest to college students. We used this insight to design and implement a multidisciplinary undergraduate course with psychoactive drugs as the central theme. The Medical Science of Psychoactive Drugs examines the biological mechanisms underlying all major effects of psychoactive drugs,…
Psychoactive constituents of cannabis and their clinical implications: a systematic review.

PubMed

Casajuana Köguel, Cristina; López-Pelayo, Hugo; Balcells-Olivero, Mª Mercedes; Colom, Joan; Gual, Antoni

2018-04-15

Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to cannabis psychoactivity, considering their reported concentrations and pharmacodynamics in humans. Design Following PRISMA guidelines, papers published before March 2016 in Medline, Scopus-Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a-priori selection criteria have been included. Results In 40 original papers, three naturally present cannabinoids (∆-9-Tetrahydrocannabinol, ∆-8-Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had clinical relevance. Of these, the metabolite produces the greatest psychoactive effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on cannabis psychoactive effects. The proportion of 9-THC in plant material is higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports vary due to differences in methodological aspects (doses, administration route and volunteers' previous experience with cannabis). Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity. Due to lower psychoactive potency and smaller proportions in plant material, other psychoactive cannabinoids have a weak influence on cannabis final effects. Current lack of standard methodology hinders homogenized research on cannabis health effects. Working on a standard cannabis unit considering 9-THC is recommended.
Toxicokinetics of novel psychoactive substances: characterization of N-acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C designer drugs.

PubMed

Meyer, Markus R; Robert, Anja; Maurer, Hans H

2014-06-05

The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called "2Cs") recently became of great importance on the illicit drug market as stimulating hallucinogens. They are distributed and consumed as "novel psychoactive substances" (NPS) without any safety testing at the forefront. As previous studies have shown, the 2Cs are mainly metabolized by O-demethylation, N-acetylation, or deamination. Therefore, the aim of this study was to elucidate the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in the phase II metabolism of 2Cs. For these studies, cDNA-expressed recombinant human NATs were used and formation of metabolites after incubation was measured using GC-MS. NAT2 could be shown to be the only isoform catalyzing the reaction in vitro, hence it should be the only relevant enzyme for in vivo acetylation. In general, all metabolite formation reactions followed classic Michaelis-Menten kinetics and the affinity to human NAT2 was increasing with the volume of the 4-substituent. In consequence, a slow acetylator phenotype or inhibition of NAT2 could lead to decreased N-acetylation and might lead to an increased risk of side effects caused by these novel psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Drugs for youth via Internet and the example of mephedrone.

PubMed

Vardakou, I; Pistos, C; Spiliopoulou, Ch

2011-03-25

Recently a new class of "designer drugs" has emerged on the drugs abuse market, known as "legal highs". Such drugs are legal to use and possess, and legal to supply. Mephedrone, a central nervous system stimulant, is the most widely experienced "legal high". This review presents any available information about psychoactive properties, safety profile, clinical data, and legislation of the new "legal high" and emphasizes the role of Internet with mephedrone's expansion. Available data were collected by various literature search engines and World Wide Web. All valuable information about psychoactive properties, safety profile and clinical data for mephedrone and its use as "legal high" were managed to spot and summarise. Internet plays a significant role for the distribution of "legal highs", becoming one of the major "drug market". Adolescents and young adults who are curious about drugs may search on the Internet and thereby become exposed to thousands of sites that expound upon the positive effects of drugs and downplay or deny any negative effects. Use of mephedrone is mainly a youth phenomenon. The hazardous side-effects are strong desire to re-dose, uncomfortable changes in body temperature and heart rate, hallucinations and psychosis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model.

PubMed

Lim, Chae-Seok; Hoang, Elizabeth T; Viar, Kenneth E; Stornetta, Ruth L; Scott, Michael M; Zhu, J Julius

2014-02-01

Fragile X syndrome, caused by the loss of Fmr1 gene function, is the most common form of inherited mental retardation, with no effective treatment. Using a tractable animal model, we investigated mechanisms of action of a few FDA-approved psychoactive drugs that modestly benefit the cognitive performance in fragile X patients. Here we report that compounds activating serotonin (5HT) subtype 2B receptors (5HT2B-Rs) or dopamine (DA) subtype 1-like receptors (D1-Rs) and/or those inhibiting 5HT2A-Rs or D2-Rs moderately enhance Ras-PI3K/PKB signaling input, GluA1-dependent synaptic plasticity, and learning in Fmr1 knockout mice. Unexpectedly, combinations of these 5HT and DA compounds at low doses synergistically stimulate Ras-PI3K/PKB signal transduction and GluA1-dependent synaptic plasticity and remarkably restore normal learning in Fmr1 knockout mice without causing anxiety-related side effects. These findings suggest that properly dosed and combined FDA-approved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome.
Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736
Analysis of legal high materials by ultra-performance liquid chromatography with time of flight mass spectrometry as part of a toxicology vigilance system: what are the most popular novel psychoactive substances in the UK?

PubMed

Ford, Loretta T; Berg, Jonathan D

2017-03-01

Introduction Legal highs also known as novel psychoactive substances mimic the effects of classic drugs of abuse. Challenges to developing screening services for novel psychoactive substances include identifying which novel psychoactive substances are available to target. Using new techniques such as exact mass time of flight can help identify common novel psychoactive substances to target for screening patient samples by routine methods such as tandem mass spectrometry. We demonstrate this strategy working in our own clinical toxicology laboratory after qualitative analysis of 98 suspect materials for novel psychoactive substances by ultra-performance liquid chromatography with time of flight mass spectrometry. Results From July 2014 to July 2015 we received 98 requests to test a range of different suspect materials for novel psychoactive substances including herbs, tobacco, liquids, pills and powders. Overall, 87% of the suspect materials tested positive for novel psychoactive substances, and 15% for controlled drugs. Three common novel psychoactive substances were present in 74% of the suspect materials: methiopropamine, a methamphetamine analogue; ethylphenidate, a cocaine mimic; and the third generation synthetic cannabinoid 5F-AKB-48. For the 55 branded products we tested only 24% of the stated contents matched exactly the compounds we detected. Conclusion Testing suspect materials using ultra-performance liquid chromatography with time of flight mass spectrometry has identified three common novel psychoactive substances in use in the UK, simplifying the development of a relevant novel psychoactive substances screening service to our population. By incorporating this into our routine liquid chromatography tandem mass spectrometry drugs of abuse screen, then offers a clinically relevant novel psychoactive substances service to our users. This strategy ensures our clinical toxicology service continues to remain effective to meet the challenges of the changing drug use in the UK.
Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.
Poppers: legal highs with questionable contents? A case series of poppers maculopathy.

PubMed

Rewbury, Rebecca; Hughes, Edward; Purbrick, Robert; Prior, Stephen; Baron, Mark

2017-11-01

Poppers are volatile alkyl nitrite compounds that are inhaled to enhance sexual experience and for their psychoactive effects. A less well-known side effect is foveal maculopathy, which has emerged following changes in their chemical composition. It is unclear if certain individuals are more susceptible to retinal damage or if there is a relationship between pattern of inhalation and brands used. A case series of 12 patients presenting to Sussex Eye Hospital, Brighton, with poppers-related visual impairment. Follow-up data were available in 10 cases, at a median time interval of 5 months (range 0-31 months). Eight samples of poppers were analysed using proton nuclear magnetic resonance spectroscopy. Patients presented with disrupted central vision occurring soon after inhalation. All demonstrated disruption of the inner segment/outer segment junction on spectral domain optical coherence tomography. Six of the brands implicated in causing visual symptoms contained isopropyl nitrite, while Jungle Juice Plus varieties, used without side effects in one case, contained amyl nitrite, 2-methyl butyl nitrite and isobutyl alcohol. In general, symptomatic resolution, alongside partial, if not full, recovery of foveal architecture was observed following abstention. On the basis of the products tested here, it seems that isopropyl nitrite is toxic to the fovea and can cause significant visual disturbance. The production of poppers is unregulated and their popularity is concerning, particularly given their exemption from the Psychoactive Substances Act 2016, which might suggest that they are harmless chemicals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.

PubMed

Cinosi, Eduardo; Martinotti, Giovanni; Simonato, Pierluigi; Singh, Darshan; Demetrovics, Zsolt; Roman-Urrestarazu, Andres; Bersani, Francesco Saverio; Vicknasingam, Balasingam; Piazzon, Giulia; Li, Jih-Heng; Yu, Wen-Jing; Kapitány-Fövény, Máté; Farkas, Judit; Di Giannantonio, Massimo; Corazza, Ornella

2015-01-01

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.
Monoamine transporter and receptor interaction profiles in vitro predict reported human doses of novel psychoactive stimulants and psychedelics.

PubMed

Luethi, Dino; Liechti, Matthias E

2018-05-29

Pharmacological profiles of new psychoactive substances (NPSs) can be established rapidly in vitro and provide information on potential psychoactive effects in humans. The present study investigated whether specific in vitro monoamine transporter and receptor interactions can predict effective psychoactive doses in humans. We correlated previously assessed in vitro data of stimulants and psychedelics with human doses that are reported on the Internet and in books. For stimulants, dopamine and norepinephrine transporter inhibition potency was positively correlated with human doses, whereas serotonin transporter inhibition potency was inversely correlated with human doses. Serotonin 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2C receptor affinity was significantly correlated with psychedelic doses, but 5-HT1A receptor affinity and 5-HT2A and 5-HT2B receptor activation potency were not. The rapid assessment of in vitro pharmacological profiles of NPSs can help to predict psychoactive doses and effects in humans and facilitate the appropriate scheduling of NPSs.
Plants with possible psychoactive effects used by the Krahô Indians, Brazil.

PubMed

Rodrigues, Eliana; Carlini, E A

2006-12-01

In spite of the richness of the Brazilian biodiversity, no phytomedicines have been developed from this flora with the purpose of being used in psychiatric treatments. The objective of the present study was to document the use of plants with possible psychoactive effects in rituals performed by the Krahô Indians, who live in the cerrado savannahs biome in the central region of Brazil. Also, the present data were compared with the data obtained during a review of the literature on the use of psychoactive plants by 25 Brazilian indigenous groups. The study was carried out during two years of fieldwork during which anthropological and botanical methods were employed. Seven local shamans were interviewed and they indicated 98 formulas, consisting of 45 plant species that appear to have psychoactive properties and were used in 25 different treatments. Some of the psychoactive properties were "prevention of madness", "stimulant effect", "tranquilizing effect", "prevention of tremors", "longer sleeping period", "open mind" and "induction of sleep". This article also describes the review of literature, which recorded 58 plants that may have psychoactive effects used by 25 Brazilian Indian cultures. The treatment of psychological/psychiatric disorders based on the plants used by the Krahô Indians is very rich. It is also observed among other Brazilian indigenous groups. Future phytochemical and pharmacological studies on these plants may develop new medicines to treat psychiatric disorders.
A critical examination of the definition of 'psychoactive effect' in Australian drug legislation.

PubMed

Barratt, Monica J; Seear, Kate; Lancaster, Kari

2017-02-01

As the number of new 'psychoactive substances' detected globally has risen exponentially, the policy response of assessing and prohibiting each new substance individually has become increasingly unworkable. In an attempt to disrupt the availability of new as-yet-unscheduled substances, Ireland (2010), Poland (2011), Romania (2012), New Zealand (2013), Australia (2015) and the United Kingdom (2016) have enacted generic or blanket ban legislation that prohibits all 'psychoactive substances' that are not already regulated or belong to exempt categories. How such generic legislation defines 'psychoactive substance' is therefore crucial. While there is a growing critical literature relating to blanket bans of 'psychoactive substances', the Australian legislation is yet to be described or critically analysed. In this commentary, we aim to draw the attention of local and international drug policy scholars to Australia's newest legislative approach to 'psychoactive substances'. Using the Australian experience as a case study, we first describe and trace the origins of this generic banning approach, especially focusing on how 'psychoactive effect' came to be defined. Then, we critically examine the assumptions underpinning this definition and the possibilities silenced by it, drawing on the work of poststructuralist and critical scholars. In doing so, we explore and raise a series of questions about how this legislation works to stabilise drugs, drug harms and drug effects, as well as addiction realities; how the category of 'psychoactive substances' is produced through this legislation; and some of the material-discursive effects which accompany this rendering of the 'problem'. We offer this commentary not as a comprehensive discussion of each of these elements but rather as a starting-point to promote further discussion and debate within the drug policy field. To this end, we conclude with a suggested research agenda that may help guide such future work. Copyright © 2016 Elsevier B.V. All rights reserved.
Are there any potentially dangerous pharmacological effects of combining ADHD medication with alcohol and drugs of abuse? A systematic review of the literature.

PubMed

Barkla, Xanthe M; McArdle, Paul A; Newbury-Birch, Dorothy

2015-10-30

Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.
"Not for human consumption": a review of emerging designer drugs.

PubMed

Musselman, Megan E; Hampton, Jeremy P

2014-07-01

Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.
Exploration of the Use of New Psychoactive Substances by Individuals in Treatment for Substance Misuse in the UK

PubMed Central

Guirguis, Amira; Schifano, Fabrizio

2018-01-01

Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored strategies. The purpose of this qualitative study was to identify and explore key themes in relation to the use of NPS by individuals receiving community treatment for their substance use. Electronic records identified demographics and semi-structured interviews were undertaken. A thematic analysis of transcripts identified a variety of substance use histories; 50% were prescribed opiate substitutes and 25% used NPS as a primary substance. All were males, age range 26–59 years (SD = 9), who predominantly smoked cannabinoids and snorted/injected stimulant NPS. The type of NPS used was determined by affordability, availability, side-effect profile and desired effects (physical and psychological: 25% reported weight loss as motivation for their use). Poly-pharmacy, supplementation and displacement of other drugs were prevalent. In conclusion, NPS use and associated experiences vary widely among people receiving substance use treatment. Development of effective recovery pathways should be tailored to individuals, and include harm reduction strategies, psychosocial interventions, and effective signposting. Services should be vigilant for NPS use, “on top” use and diversion of prescriptions. PMID:29601550
Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

PubMed

Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

2011-02-01

The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.
Cannabinoid signaling in health and disease.

PubMed

Lu, Yan; Anderson, Hope D

2017-04-01

Cannabis sativa has long been used for medicinal purposes. To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids. Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain. More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection. The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear. In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects. This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.
Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery.

PubMed

Roth, Bryan L; Lopez, Estela; Beischel, Scott; Westkaemper, Richard B; Evans, Jon M

2004-05-01

Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies.
Herbal Highs: Review on Psychoactive Effects and Neuropharmacology

PubMed Central

Graziano, Silvia; Orsolini, Laura; Rotolo, Maria Concetta; Tittarelli, Roberta; Schifano, Fabrizio; Pichini, Simona

2017-01-01

Background: A new trend among users of new psychoactive substances’ the consumption of “herbal highs”: plant parts containing psychoactive substances. Most of the substances extracted from herbs, in old centuries were at the centre of religious ceremonies of ancient civilizations. Currently, these herbal products are mainly sold by internet web sites and easily obtained since some of them have no legal restriction. Objective: We reviewed psychoactive effects and neuropharmacology of the most used “herbal highs” with characterized active principles, with studies reporting mechanisms of action, pharmacological and subjective effects, eventual secondary effects including intoxications and/or fatalities Method: The PubMed database was searched using the following key.words: herbal highs, Argyreia nervosa, Ipomoea violacea and Rivea corymbosa; Catha edulis; Datura stramonium; Piper methysticum; Mitragyna speciosa. Results: Psychoactive plants here reviewed have been known and used from ancient times, even if for some of them limited information still exist regarding subjective and neuropharmacological effects and consequent eventual toxicity when plants are used alone or in combination with “classical” drugs of abuse. Conclusion: Some “herbal highs” should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking. PMID:27799032
Herbal Highs: Review on Psychoactive Effects and Neuropharmacology.

PubMed

Graziano, Silvia; Orsolini, Laura; Rotolo, Maria Concetta; Tittarelli, Roberta; Schifano, Fabrizio; Pichini, Simona

2017-01-01

A new trend among users of new psychoactive substances' the consumption of "herbal highs": plant parts containing psychoactive substances. Most of the substances extracted from herbs, in old centuries were at the centre of religious ceremonies of ancient civilizations. Currently, these herbal products are mainly sold by internet web sites and easily obtained since some of them have no legal restriction. We reviewed psychoactive effects and neuropharmacology of the most used "herbal highs" with characterized active principles, with studies reporting mechanisms of action, pharmacological and subjective effects, eventual secondary effects including intoxications and/or fatalities Method: The PubMed database was searched using the following key.words: herbal highs, Argyreia nervosa, Ipomoea violacea and Rivea corymbosa; Catha edulis; Datura stramonium; Piper methysticum; Mitragyna speciosa. Psychoactive plants here reviewed have been known and used from ancient times, even if for some of them limited information still exist regarding subjective and neuropharmacological effects and consequent eventual toxicity when plants are used alone or in combination with "classical" drugs of abuse. Some "herbal highs" should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-01-01

Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745
Could cannabidiol be used as an alternative to antipsychotics?

PubMed

Fakhoury, Marc

2016-09-01

Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. Copyright © 2016 Elsevier Ltd. All rights reserved.
Medication for Behavior Modification in Birds.

PubMed

van Zeeland, Yvonne

2018-01-01

The use of behavior modifying drugs may be considered in birds with behavior problems, especially those refractory to behavior modification therapy and environmental management. To accomplish behavior change, a variety of drugs can be used, including psychoactive drugs, hormones, antihistamines, analgesics, and anticonvulsants. Because their prescription to birds is off-label, these drugs are considered appropriate only when a sound rationale can be provided for their use. This requires a (correct) behavioral diagnosis to be established. In addition, regular monitoring and follow-up are warranted to determine the efficacy of the treatment and evaluate the occurrence of potential adverse side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use.

PubMed

Bowblis, John R; Lucas, Judith A; Brunt, Christopher S

2015-08-01

The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare's initiation of publicly reporting antipsychotic use in July 2012. The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting. The percentage of residents using antipsychotics, hypnotics, or any psychoactive medication is found to decline after public reporting. Facilities subject to reporting experienced an additional decline in antipsychotic use (-1.94 vs. -1.40 percentage points) but did not decline as much for hypnotics (-0.60 vs. -1.21 percentage points). Any psychoactive use did not vary with reporting status, and the use of antidepressants and anxiolytics did not change. Public reporting of an antipsychotic quality measure can be an effective policy tool for reducing the use of antipsychotic medications--though the effect many only exist in the short run. © Health Research and Educational Trust.
Differences in Psychoactive Substance Abuse Between Youths Residing in and Outside Conflict Zones as a Function of Level of Religiosity and Political Commitment.

PubMed

Ne'eman-Haviv, Vered; Wilchek-Aviad, Yael

2017-08-24

The aim of the present study was to examine the effect of the unique characteristics of residing in security and political conflict zones on the willingness to use and on the actual abuse of psychoactive substances. The study focuses on the differences between youths residing in and outside conflict zones in Israel. The present study examines the link between the adolescents' level of psychoactive substance abuse and town size as well as the youths' level of ideological commitment and religiosity. 1032 adolescents aged 14-18 participated in the study. 595 (57%) lived in the nonconflict zones and 437 (43%) in conflict zones. The findings reveal that the level of psychoactive substance abuse among youths residing in conflict zones is significantly lower than that found among youths living outside conflict zones. Moreover, although town size and level of religiosity are linked to psychoactive substance abuse, no such link was found with the level of ideological commitment or place of residence (within or outside conflict zones). The study findings underscore the important effect of social supervision and perceived norms in the adolescents' environment with regard to their willingness to use psychoactive substances and to their actual abuse of such substances.
Psyclones: a roller coaster of life? Hidden synthetic cannabinoids and stimulants in apparently harmless products.

PubMed

Santacroce, Rita; Corazza, Ornella; Martinotti, Giovanni; Bersani, Francesco Saverio; Valeriani, Giuseppe; Di Giannantonio, Massimo

2015-07-01

The urge to gain information on a new drug marketed online as 'Psyclone' has emerged after the death of a 38-year-old man in Bolton (UK). The fatality appeared to be a consequence of smoking this psychoactive product. From October to December 2013, qualitative searches of the Web have been carried out in English and Italian, using the keywords 'Psyclone', 'Psyclone legal high', 'Psyclone incense' and 'Psyclone research chemical' on the Google search engine and on the database provided by the Global Public Health Intelligence Network. Our research highlighted the existence of two psychoactive products labelled as Psyclone but with different contents and packaging: a herbal blend containing two synthetic cannabinoids (AKB-48 and 5f-PB-22) and a research chemical containing 50% ethylphenidate, 30% caffeine and 20% lidocaine. Desired and side effects of both compounds are explored in the paper. Being sold as a legal product, Psyclone may appeal to recreational users, who remain unaware of its real content. This is a serious public health threat, which may lead to acute intoxications and fatalities. Further studies in the field, including Internet monitoring, are therefore required. Copyright © 2015 John Wiley & Sons, Ltd.
Following “the Roots” of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries

PubMed Central

Cinosi, Eduardo; Martinotti, Giovanni; Simonato, Pierluigi; Singh, Darshan; Demetrovics, Zsolt; Roman-Urrestarazu, Andres; Bersani, Francesco Saverio; Vicknasingam, Balasingam; Piazzon, Giulia; Li, Jih-Heng; Yu, Wen-Jing; Kapitány-Fövény, Máté; Farkas, Judit; Di Giannantonio, Massimo; Corazza, Ornella

2015-01-01

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon. PMID:26640804
[Vegetables as new psychoactive drugs: a narrative review].

PubMed

Rodríguez Salgado, Beatriz; Gómez-Arnau Ramírez, Jorge; Sánchez Mateos, Daniel; Dolengevich Segal, Helen

2016-01-21

There is growing interest in plants with psychoactive effects among consumers with different levels of experience. This has generated a need for updated knowledge among medical professionals and other health workers. These plants, which may be used in shamanic healing ceremonies or rituals or just for traditional purposes, have emerged in the Western world as new psychoactive drugs; largely thanks to the ease of purchase, sale, cultivation and exchange of information that the Internet offers. This review summarizes the current knowledge about the most important psychoactive plants, either by their mention in Internet forums or harm-reduction portals or by their allusion in scientific texts.
Symbolism and rationality in the politics of psychoactive substances.

PubMed

Room, Robin

2005-01-01

Psychoactive substances take on many symbolic meanings, and thus the politics of psychoactive substances has featured symbolic elements, or value-based rationality, alongside and often dominating instrumental rationality. Drawing particularly on the work of Joseph Gusfield and Nordic scholars, the chapter considers the symbolic dimension in the politics of substance use, even in Nordic countries celebrated for their societal commitment to knowledge-based policymaking, and its effects on the interplay of science and policy.
Alcohol and Psychoactive Substance Use among University Students in Edirne and Related Parameters

PubMed Central

GÖRGÜLÜ, Yasemin; ÇAKIR, Diğdem; SÖNMEZ, Mehmet Bülent; KÖSE ÇINAR, Rugül; VARDAR, Mehmet Erdal

2016-01-01

Introduction Alcohol and psychoactive substance use and their effects are an important issue among adolescents and young adults. Different results have been reported about the frequency of alcohol and psychoactive substance use among university students in studies conducted both in Turkey and in different places worldwide. Methods The frequency of alcohol and psychoactive substance use among Trakya University students (n=1385) and the related parameters were studied cross-sectionally using a self-reporting questionnaire. Results Alcohol was the most common substance used (30%), followed by tobacco (29.9%) and marijuana (3.1%). The frequency of alcohol and psychoactive substance use was found to be higher among males with higher amounts of pocket money, whose parents experienced more conflict in their relationship, and who belong to families with a higher education and income level. Conclusion The frequency of alcohol and psychoactive substance use among Trakya University students was found to be lower than other regions in Turkey and particularly lower than the levels reported in studies conducted in other countries. PMID:28360790
Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function.

PubMed

Eshleman, Amy J; Forster, Michael J; Wolfrum, Katherine M; Johnson, Robert A; Janowsky, Aaron; Gatch, Michael B

2014-03-01

Psychoactive-substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2); and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. This study compares the behavioral effects and the mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant. The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (-)-DOM, (+)-LSD, (±)-MDMA, and S(+)-methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins. The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound, but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter. The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I, and DOC were similar to those of several hallucinogens, but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogen-like discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I's psychoactive properties.
Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: Mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function

PubMed Central

Eshleman, Amy J.; Forster, Michael J.; Wolfrum, Katherine M.; Johnson, Robert A.; Janowsky, Aaron; Gatch, Michael B.

2014-01-01

Rationale Psychoactive substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. Objectives This study compares behavioral effects and mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant. Methods The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (−)DOM, (+)LSD, (±)MDMA and (S+)methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins. Results The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter. Conclusions The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I and DOC were similar to those of several hallucinogens but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogenlike discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I’s psychoactive properties. PMID:24142203
Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.
Drugs as instruments: a new framework for non-addictive psychoactive drug use.

PubMed

Müller, Christian P; Schumann, Gunter

2011-12-01

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.
Psychoactive Medication and Learning Disabilities

ERIC Educational Resources Information Center

Eaton, Marie; And Others

1977-01-01

A seven-year-old emotionally disturbed boy with some features of the hyperkinetic syndrome was placed on a double-blind placebo control program to assess the effects of psychoactive medications (Ritalin and Dexedrine) on academic and social behaviors. (Author)
The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use

PubMed Central

Bowblis, John R; Lucas, Judith A; Brunt, Christopher S

2015-01-01

Objective The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare’s initiation of publicly reporting antipsychotic use in July 2012. Research Design and Subjects The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting. Principal Findings The percentage of residents using antipsychotics, hypnotics, or any psychoactive medication is found to decline after public reporting. Facilities subject to reporting experienced an additional decline in antipsychotic use (−1.94 vs. −1.40 percentage points) but did not decline as much for hypnotics (−0.60 vs. −1.21 percentage points). Any psychoactive use did not vary with reporting status, and the use of antidepressants and anxiolytics did not change. Conclusion Public reporting of an antipsychotic quality measure can be an effective policy tool for reducing the use of antipsychotic medications—though the effect many only exist in the short run. PMID:25600861
A market on both "sides" of the law: The use of the hidden web for the sale of new psychoactive substances.

PubMed

Wadsworth, Elle; Drummond, Colin; Kimergård, Andreas; Deluca, Paolo

2017-05-01

The hidden Web is used for the anonymous sale of drugs, and with the UK Psychoactive Substances Act, 2016, implemented on May 26th 2016; it could increase as a platform for obtaining new psychoactive substances (NPS). This study aims to describe the NPS market on the visible and hidden Web preban, and assess whether the hidden Web is a likely place for the sale of NPS postban. Data collection of 113 online shops took place in October 2015. Data collection of 22 cryptomarkets took place every 2 months from October 2015 to 2016 as part of the CASSANDRA project. All online shops with a UK domain location sold NPS that were uncontrolled by the UK Misuse of Drugs Act, 1971, and closed after the ban. Of the cryptomarkets analysed, the total number of vendors selling NPS, number of substances, and listings advertised, all increased over the year. The majority of the NPS advertised on the hidden Web were phenethylamines and cathinones, yet the majority of uncontrolled NPS were synthetic cannabinoids. Vendors selling and availability of NPS increased over the 12 months of data collection. Potential displacement from the visible Web to hidden Web should be taken into consideration. Copyright © 2017 John Wiley & Sons, Ltd.
Depot naltrexone in lieu of incarceration: a behavioral analysis of coerced treatment for addicted offenders.

PubMed

Marlowe, Douglas B

2006-09-01

This article is part of a series of articles examining a proposal to offer depot naltrexone to certain nonviolent opiate-addicted criminal offenders in exchange for release from incarceration or diversion from prosecution. This "negative-reinforcement" behavioral paradigm could have a better chance of success than what has heretofore been attempted with drug-abusing offenders. Traditional correctional efforts have been largely unsuccessful due to the complexities of implementation and the side effects of punishment. Although positive reinforcement can be more efficacious, it has often been strenuously resisted on the ground that it is inequitable to reward antisocial individuals for doing what is minimally expected of most citizens. Negative reinforcement steers between these hurdles by avoiding the iatrogenic effects of punishment, while also being palatable to stakeholders. More research is needed to identify the effects, costs, and side effects of negative-reinforcement arrangements for drug offenders. The current proposal provides an excellent platform for conducting this research because the target intervention (depot naltrexone) is demonstrably efficacious, nonpsychoactive, and has few, if any, side effects. Therefore, use of this medication would be unlikely to invoke the same types of legal and ethical objections that have traditionally been levied against the use of psychoactive medications with vulnerable populations of institutionalized offenders. Specific recommendations are offered for questions that must be addressed in future research studies.
International aspects of problems associated with the use of psychoactive drugs.

PubMed

Chruściel, T L

1976-01-01

Problems of terminology, use and consumption, advertising, effectiveness and appropriate information and education on psychoactive drugs are outlined and advantages of international collaboration in attempts to establish standards for controlled clinical trials in psychopharmacology are discussed.
Recreational Use, Analysis and Toxicity of Tryptamines

PubMed Central

Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio

2015-01-01

The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a “legal” alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews. Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances. Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora. Conclusions: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department. PMID:26074742
[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

PubMed

Mathalone, Nurit; Wolf, Alvit; Geyer, Orna

2015-06-01

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.
Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive Substances: A Systematic Review.

PubMed

Eserian, Jaqueline K; Lombardo, Márcia; Chagas, Jair R; Galduróz, José C F

2018-02-08

To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting. © Copyright 2018 Physicians Postgraduate Press, Inc.
Latest advances in novel cannabinoid CB2 ligands for drug abuse and their therapeutic potential

PubMed Central

Yang, Peng; Wang, Lirong; Xie, Xiang-Qun

2012-01-01

The field of cannabinoid (CB) drug research is experiencing a challenge as the CB1 antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB2 drugs without CB1 psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB1 receptor was discovered predominantly in the brain, whereas the CB2 is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB2 receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB2 neurons activity remains controversial, the CB2 receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB2 ligands from the literature as well as patents. PMID:22300098

Novel psychoactive substances of interest for psychiatry

PubMed Central

Schifano, Fabrizio; Orsolini, Laura; Duccio Papanti, G; Corkery, John M

2015-01-01

Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed. PMID:25655145
What matters to patients? A systematic review of preferences for medication-associated outcomes in mental disorders

PubMed Central

Eiring, Øystein; Landmark, Brynjar Fowels; Aas, Endre; Salkeld, Glenn; Nylenna, Magne

2015-01-01

Objective To investigate patients’ preferences for outcomes associated with psychoactive medications. Setting/design Systematic review of stated preference studies. No settings restrictions were applied. Participants/eligibility criteria We included studies containing quantitative data regarding the relative value adults with mental disorders place on treatment outcomes. Studies with high risk of bias were excluded. Primary and secondary outcome measures We restricted the scope of our review to preferences for outcomes, including the consequences from, attributes of, and health states associated with particular medications or medication classes, and process outcomes. Results After reviewing 11 215 citations, 16 studies were included in the systematic review. These studies reported the stated preferences from patients with schizophrenia (n=9), depression (n=4), bipolar disorder (n=2) and attention deficit hyperactive disorder (n=1). The median sample size was 81. Side effects and symptom outcomes outnumbered functioning and process outcomes. Severe disease and hospitalisation were reported to be least desirable. Patients with schizophrenia tended to value disease states as higher and side effects as lower, compared to other stakeholder groups. In depression, the ability to cope with activities was found to be more important than a depressed mood, per se. Patient preferences could not consistently be predicted from demographic or disease variables. Only a limited number of potentially important outcomes had been investigated. Benefits to patients were not part of the purpose in 9 of the 16 studies, and in 10 studies patients were not involved when the outcomes to present were selected. Conclusions Insufficient evidence exists on the relative value patients with mental disorders place on medication-associated outcomes. To increase patient-centredness in decisions involving psychoactive drugs, further research—with outcomes elicited from patients, and for a larger number of conditions—should be undertaken. Trial registration number PROSPERO CRD42013005685. PMID:25854979
Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

NASA Astrophysics Data System (ADS)

Wenthur, Cody J.; Zhou, Bin; Janda, Kim D.

2017-08-01

Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and ‘pharmacoterrorism’ in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.
Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity.

PubMed

Wenthur, Cody J; Zhou, Bin; Janda, Kim D

2017-08-24

Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a 'dissection through vaccination' approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.
The challenge of a ban on animal testing for the development of a regulated legal market for new psychoactive substances (NPS) ('legal highs') in New Zealand: Issues and options for resolution.

PubMed

Rychert, Marta; Wilkins, Chris

2015-12-01

In mid-July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which allowed 'low risk' psychoactive products ('legal highs') to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable. To investigate strategies to overcome the impasse created by the animal testing ban. Solutions to the impasse were investigated using 'scenario' and 'stakeholder' analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision-making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators. The six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non-animal test models are internationally accepted; (3) use of non-validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) 'creative compliance' by only presenting human clinical trial results; and (6) philosophical re-conceptualisation of the 'benefits' from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays. A 'failed' pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be included in the debate. Copyright © 2015 Elsevier B.V. All rights reserved.
Separation of enantiomers of new psychoactive substances by high-performance liquid chromatography.

PubMed

Kadkhodaei, Kian; Forcher, Lisa; Schmid, Martin G

2018-03-01

New psychoactive substances are defined as compounds with consciousness-changing effects and have been developed simultaneously with classical drugs. They arise through structural modifications of illegal substances and are mainly produced to circumvent laws. Availability is simple, since new psychoactive substances can be purchased from the Internet. Among them many chemical drug compound classes are chiral and thus the two resulting enantiomers can differ in their effects. The aim of this study is to develop a suitable chiral high-performance liquid chromatography separation method for a broad spectrum of new psychoactive substances using cellulose tris(3,5-dichlorophenylcarbamate) as a chiral selector. Experiments were performed by high-performance liquid chromatography in normal-phase mode under isocratic conditions using ultraviolet detection. Direct separation was carried out on a high-performance liquid chromatography column (Lux® i-Cellulose-5, 3.5 μm, Phenomenex®), available since 2016. Excellent separation results were obtained for cathinones. After further optimization, even 47 instead of 39 out of 52 cathinones showed baseline separation. For amphetamine derivatives, satisfactory results were not achieved. Further, new psychoactive substances from other compound classes such as benzofuranes, thiophenes, phenidines, phenidates, morpholines, and ketamines were partially resolved, depending on the polarity and degree of substitution. All analytes, which were mainly purchased from the Internet, were proven to be traded as racemates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
A Qualitative Study on the Effects of Psychoactive Substance use upon Artistic Creativity.

PubMed

Iszaj, Fruzsina; Ehmann, Bea; Griffiths, Mark D; Demetrovics, Zsolt

2017-11-29

Psychoactive substance use has often been claimed to help generate and facilitate the artistic creative process. This study explored the role of artists' substance use in their creative processes and their efforts to balance between enhancement and relaxation. Semistructured interviews concerning the artistic creative process and the role of psychoactive substance use were recorded with 72 artists and analyzed using content analysis. The participants were classified according to their substance use in three groups (Cannabis Group, Alcohol Group, and Control Group). Results show that both alcohol and cannabis were used to facilitate creativity and the emotional states that are necessary for the artistic creative process. Participants in the Control group reported that listening to music might function as a mind-altering tool. It was also found that for some artists, substance use is not only characteristic to creation, but it is also part of their everyday lives. Artists are aware of the balancing phenomenon during the artistic creative process. Whether psychoactive substance(s) or other environmental stimuli (such as music) are used to reach the required effect appears to depend upon the individual.
Chromatography as Method for Analytical Confirmation of Paracetamol in Postmortem Material Together with Psychoactive Substances.

PubMed

Biscevic-Tokic, Jasmina; Tokic, Nedim; Ibrahimpasic, Elma

2015-10-01

Paracetamol (Acetaminophen) in addition to aspirin is the most commonly used analgesic and antipyretic medication by millions of patients worldwide. It is an example that paracetamol as medicine that in the world is provided without a doctor's prescription, can lead to death. Today paracetamol became an integral part of a heroin mixture and is very popular at the street market. The main reason for this is that it can be obtained without a prescription, it is cheap, and by most people well tolerated without side effects. It is probably used for "cutting" the pure heroin, as it says in the jargon, and in that manner from small amount of pure drug is obtained greater amount, which is then sold on the street. The goal is to identify presence of paracetamol, by analytical method of gas chromatography mass spectrometer (GC-MS) in postmortem material together with psychoactive substances. For chemical-toxicological analysis is used biological material collected trough autopsy of 20 deceased people, suspected to have died due to psychoactive substance overdose. All received samples are stored at -20 ° C until analysis at our laboratory. From processed 47 samples that were analyzed in the period from 2014 to 2015, 19 are blood samples, urine 19, 3 samples of stomach contents, and 6 samples of bile content. Deceased were middle-aged, of which only 7 were female. The tested samples were processed according to two methods of extraction. Extraction by XAD-2 resin, and the extraction by the method of salting out with sodium tungstate. Extracts of the samples were then dissolved in chloroform and continued analysis at the analytical instrument. Identification of the paracetamol presence, in the test biological samples is demonstrated by the technique of gas chromatography with mass spectometry (hereinafter referred to as GC-MS). The technique of GC-MS is a selective, sensitive and reliable, and is therefore considered a "gold standard" for determining the drug, and the drug substance. Used GC-MS instrument was an Agilent 7890A with helium as the carrier gas. The analysis of blood samples, urine, bile and stomach contents, obtained after the autopsy of deceased persons, by using gas chromatography with mass spectrometry, in analytical manner confirmed the fact that paracetamol is a very common component of psychoactive substances poisoning. In our assay of samples we detected psychoactive substances (heroin, codeine, morphine, sertraline, diazepam), and almost all were found in the combination with paracetamol, indicating the poor quality of illicit drugs sold on the market. Paracetamol (Acetaminophen) is a very common component in mixtures of street drugs. Such mixtures almost anyone can afford, but the very quality of these drugs has become extremely low, because it does not sell the pure substance, but is mixed with various medications. According to research Pantazia et al. the heroin mixture proportion of the heroin is very small so a lot of that mixture has only 3% of heroin, a large number of cases can be only 1% of pure heroin. Most of the time it replaces caffeine and paracetamol. According to the Risser et al. reason why acetaminophen component is present in these mixtures is because it can be purchased without a prescription, it is cheap, well tolerated by most people and shows no side effects. When we talk about illegal drugs, we must emphasize the fact that there is no quality control, or the composition of the drug. The composition of the drug purchased on the black market is still unknown to potential user. While reaching the final drug users it pass through many hands, and at each step something is added to increase earnings. Most often present additives or impurities in narcotic drugs that are added are caffeine, ephedrine, acetaminophen, acetylsalicylic acid (aspirin) and additives such as powders, cement and chalk.
Towards the use of non-psychoactive cannabinoids for prostate cancer

PubMed Central

Pacher, Pál

2013-01-01

The palliative effects of Cannabis sativa (marijuana), and its putative main active ingredient, Δ9-tetrahydrocannabinol (THC), which include appetite stimulation, attenuation of nausea and emesis associated with chemo- or radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer patients, are well-known. Because of the adverse psychoactive effects of THC, numerous recent preclinical studies have been focused on investigating other non-psychoactive constituents of C. sativa, such as cannabidiol, for potential therapeutic use. In this issue of the British Journal of Pharmacology, De Petrocellis and colleagues present comprehensive evidence that plant-derived cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma viability in vitro. They also showed that the extract was active in vivo, either alone or when administered with drugs commonly used to treat prostate cancer (the anti-mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti-androgen bicalutamide (Casodex)) and explored the potential mechanisms behind these antineoplastic effects. PMID:22849856
Psychoactive drugs and false memory: comparison of dextroamphetamine and delta-9-tetrahydrocannabinol on false recognition

PubMed Central

Ballard, Michael E.; Gallo, David A.; de Wit, Harriet

2014-01-01

Rationale Several psychoactive drugs are known to influence episodic memory. However, these drugs’ effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Objectives Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ9-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger–McDermott (DRM) illusion. Methods Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. Results As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs’ effects on true memory were positively correlated with their effects on false memory. Conclusions Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories. PMID:21647577
Psychoactive drugs and false memory: comparison of dextroamphetamine and δ-9-tetrahydrocannabinol on false recognition.

PubMed

Ballard, Michael E; Gallo, David A; de Wit, Harriet

2012-01-01

Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ(9)-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger-McDermott (DRM) illusion. Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory. Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.
THE SUBJECTIVE PSYCHOACTIVE EFFECTS OF ORAL DRONABINOL STUDIED IN A RANDOMIZED, CONTROLLED CROSSOVER CLINICAL TRIAL FOR PAIN

PubMed Central

Issa, Mohammed A.; Narang, Sanjeet; Jamison, Robert N.; Michna, Edward; Edwards, Robert R.; Penetar, David M.; Wasan, Ajay D.

2014-01-01

Background Many cannabinoid medications are approved in North America or in Phase III trials, such as Dronabinol, Nabilone, or Nabiximols. Little is known about their subjective psychoactive effects when used for pain management. We hypothesized that when used for pain, dronabinol has psychoactive effects in a dose response relationship, whose peak effects are comparable to smoking marijuana. Methods With IRB approval and written consent, this was a randomized controlled trial of single dose placebo, 10 or 20 mg dronabinol in 30 chronic non-cancer pain patients taking opioids and not using marijuana. Hourly, for 8 hours during 3 monitored sessions, subjects completed the Addiction Research Center Inventory (ARCI). Comparison sample was the ARCI ratings in a study population with no pain (N=20), monitored every 30 minutes after smoking a 1.99% THC (low) and a 3.51% (high strength) marijuana cigarette. Results The 10 and 20 mg dronabinol doses had significantly elevated scores on 4/5 subscales vs. placebo over time (p<.05). Average daily morphine use, total pain relief (TOTPAR), age, gender, and baseline pain level were not significant covariates. ARCI peak effects at 2 hours were similar to peak effects of smoked marijuana at 30 minutes (p=.80, 10 mg=low, 20 mg=high strength). Conclusions In pain patients, oral dronabinol has similar psychoactive effects to smoking marijuana. This risk must be considered in any decision to prescribe cannabinoid medications for pain. PMID:24281276
The Effects of Perceived Parental Behaviors, Attitudes, and Substance-Use on Adolescent Attitudes toward and Intent To Use Psychoactive Substances.

ERIC Educational Resources Information Center

Teichman, Meir; Kefir, Ester

2000-01-01

Examines how adolescents perceive the role of parents influencing their decision to use psychoactive substances. Perceived parental rejection, acceptance, and attitudes significantly differentiated between adolescents who reported favorable attitudes toward and high intent to use substances, and those who expressed less favorable attitudes. The…
Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2012-09-01

NEY-1413 FINAL Version 8.05JAN2012 Page 5 of 45 ABBREVIATIONS AE Adverse Event AASM American Academy of Sleep Medicine BzRAs...Current use of statins, ketoconazole, prescription or over- the-counter medications or herbal supplements containing psychoactive properties or...Current use of statins, ketoconazole, prescription or over-the-counter medications or herbal supplements containing psychoactive properties or
Signal identification in addictovigilance: the functioning of the French system.

PubMed

Jouanjus, Emilie; Gibaja, Valérie; Kahn, Jean-Pierre; Haramburu, Françoise; Daveluy, Amélie

2015-01-01

The French addictovigilance network (addictovigilance: surveillance of addiction), composed of 13 Addictovigilance Centres, was set up in 1990 in order to achieve reliable surveillance and evaluation of abuse and dependence cases due to psychoactive substances (alcohol and tobacco excepted). The detection of safety signals is one of the roles of the addictovigilance centres. Signals from spontaneous reports need to be analyzed before further communication. In addictovigilance, signals may be linked to adverse effects (deaths, pathological signs), to products (new psychoactive substances with potentially dangerous effects) or to practices (new administration routes, new contexts of use). These signals are provided by numerous partners among whom the addictovigilance network has to raise awareness about information that may possibly be an alert signal. The watchful attitude of all partners will make it possible that signals will be, after analyze, considered as true alerts. The addictovigilance network collects data, assess the potential for addiction of psychoactive drugs to provide information on the risk of addiction and give opinions for public health decisions (harm reduction or prevention programs, psychoactive substances control, health alerts). © 2015 Société Française de Pharmacologie et de Thérapeutique.
Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.

PubMed

Turgeman, Ilit; Bar-Sela, Gil

2017-02-01

A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.
Determination and identification of synthetic cannabinoids and their metabolites in different matrices by modern analytical techniques - a review.

PubMed

Znaleziona, Joanna; Ginterová, Pavlína; Petr, Jan; Ondra, Peter; Válka, Ivo; Ševčík, Juraj; Chrastina, Jan; Maier, Vítězslav

2015-05-18

Synthetic cannabinoids have gained popularity due to their easy accessibility and psychoactive effects. Furthermore, they cannot be detected in urine by routine drug monitoring. The wide range of active ingredients in analyzed matrices hinders the development of a standard analytical method for their determination. Moreover, their possible side effects are not well known which increases the danger. This review is focused on the sample preparation and the determination of synthetic cannabinoids in different matrices (serum, urine, herbal blends, oral fluid, hair) published since 2004. The review includes separation and identification techniques, such as thin layer chromatography, gas and liquid chromatography and capillary electrophoresis, mostly coupled with mass spectrometry. The review also includes results by spectral methods like infrared spectroscopy, nuclear magnetic resonance or direct-injection mass spectrometry. Copyright © 2015 Elsevier B.V. All rights reserved.
Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues.

PubMed

Schifano, Fabrizio; Albanese, Antonio; Fergus, Suzanne; Stair, Jackie L; Deluca, Paolo; Corazza, Ornella; Davey, Zoe; Corkery, John; Siemann, Holger; Scherbaum, Norbert; Farre', Magi'; Torrens, Marta; Demetrovics, Zsolt; Ghodse, A Hamid

2011-04-01

Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.
Synthetic cannabinoid JWH-018 and psychosis: an explorative study.

PubMed

Every-Palmer, Susanna

2011-09-01

Aroma, Spice, K2 and Dream are examples of a class of new and increasingly popular recreational drugs. Ostensibly branded "herbal incense", they have been intentionally adulterated with synthetic cannabinoids such as JWH-018 in order to confer on them cannabimimetic psychoactive properties while circumventing drug legislation. JWH-018 is a potent cannabinoid receptor agonist. Little is known about its pharmacology and toxicology in humans. This is the first research considering the effects of JWH-018 on a psychiatric population and exploring the relationship between JWH-018 and psychotic symptoms. This paper presents the results of semi-structured interviews regarding the use and effects of JWH-018 in 15 patients with serious mental illness in a New Zealand forensic and rehabilitative service. All 15 subjects were familiar with a locally available JWH-018 containing product called "Aroma" and 86% reported having used it. They credited the product's potent psychoactivity, legality, ready availability and non-detection in drug testing as reasons for its popularity, with most reporting it had replaced cannabis as their drug of choice. Most patients had assumed the product was "natural" and "safe". Anxiety and psychotic symptoms were common after use, with 69% of users experiencing or exhibiting symptoms consistent with psychotic relapse after smoking JWH-018. Although psychological side effects were common, no one reported becoming physically unwell after using JWH-018. Three subjects described developing some tolerance to the product, but no one reported withdrawal symptoms. It seems likely that JWH-018 can precipitate psychosis in vulnerable individuals. People with risk factors for psychosis should be counseled against using synthetic cannabinoids. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2016-10-01

The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆(9)-tetrahydrocannabinol (∆(9)-THC). However, we have previously shown that a cannabis extract devoid of ∆(9)-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour. The objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure. Male Lister hooded rats were administered CBG (30-120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30-240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h. CBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120-240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased. Here, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted.

Drivers involved in road traffic accidents in Piedmont Region: psychoactive substances consumption.

PubMed

Siliquini, R; Chiadò Piat, S; Gianino, M M; Renga, G

2007-12-01

The role played by psychoactive substances in road safety has become object of increasing interest: these substances can reduce driving performance and increase accidents risk. Aims of the study are to establish the dimension of the problem and to describe the characteristics of people involved in accidents under psychoactive substance effects. Target population consists of people from 18 to 60-years-old involved in accidents afferent in Emergency Rooms. Subjects were interviewed by surveyors and a urines was collected for psychoactive substances screening. In 18.5% of people we found substance consumption. Cocaine was the most frequently detected substance (9.5%), then benzodiazepines (7.5%), methadone, morphine and marijuana (THC) (3.5%). In 5.5% of subjects more than one substance was found. Considering only illegal substances detected, female have a higher risk to be consumers (OR = 1.36) and the young age (18-35 years) seems to be at higher prevalence and risk for substance use (OR = 1.86). Considering all psychoactive substances detected, clearly the problem about substances consumption and driving is not restricted to youngest but involves all age groups. In order to decrease the number of accidents due to substance use, new prevention programmes able to involve also middle age groups should be planned.
Theoretical and conformational studies of a series of cannabinoids

NASA Astrophysics Data System (ADS)

Da Silva, Albérico B. F.; Trsic, Milan

1995-11-01

The MNDO semi-empirical method is applied to the study of a series of cannabinoids with the aim of providing an improved understanding of the structure-activity relationship (SAR). The conformation of some groups that seem important in the biological activity (psychoactivity) of these compounds is characterized. Some electronic properties, such as atomic net charges and HOMO and LUMO energies, are correlated with the psychoactive effect.
What products are considered psychoactive under New Zealand's legal market for new psychoactive substances (NPS, 'legal highs')? Implications for law enforcement and penalties.

PubMed

Rychert, Marta; Wilkins, Chris

2016-08-01

The problem of defining what psychoactive products and substances should be covered by legislation aimed at controlling new psychoactive substances (NPS; 'legal highs') is central to the current debate on designing new legislative responses to NPS. In New Zealand, implementation of the Psychoactive Substances Act 2013 (PSA) revealed uncertainties about which psychoactive products are covered by the new regime, with important implications for legal penalties. We reviewed five pieces of legislation which can cover substances with psychoactive properties: PSA, Misuse of Drugs Act (MODA), Food Act, Dietary Supplements Regulations and Medicines Act. Our analysis revealed that a number of psychoactive substances which are not MODA-scheduled may potentially fall under more than one regulatory regime, including kava, Salvia divinorum, nitrous oxide, 25I-NBOMe, and 1,3-dimethylbutylamine (DMBA). For example, kava may be classified as a food, a dietary supplement, a herbal remedy, or a psychoactive substance, depending on how it is presented (including advertising and labelling). There are considerable differences in penalties and regulatory requirements between the different legislative regimes and these may result in unnecessary prosecutions or 'gaming' of the system. We discuss a number of ways to more clearly categorize products, including a public schedule of psychoactive substances and products, demarcation criteria based on the quantity of the active ingredient, and demarcation based on 'discernible intoxication'. Routine use of forensic testing is essential to ensure appropriate prosecutions and penalties. Robust safety standards are also required in legislative regimes exempted from psychoactive substances regime to prevent 'creative compliance'. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Association between use of multiple psychoactive medicines and hospitalization for falls: retrospective analysis of a large healthcare claim database.

PubMed

Pratt, Nicole L; Ramsay, Emmae N; Kalisch Ellett, Lisa M; Nguyen, Tuan A; Barratt, John D; Roughead, Elizabeth E

2014-07-01

Little is known about the impact of taking multiple psychoactive medicines on the risk of hospitalization for falls. To identify the association between multiple psychoactive medicine use and hospitalization for falls. A retrospective cohort study was conducted between July 2011 and June 2012 in the Australian veteran population who had been dispensed at least one psychoactive medicine within the previous year. Psychoactive medicines with sedative properties included antipsychotics, anxiolytics, hypnotics, antidepressants, opioids, anti-epileptics, anti-Parkinson medicines and medicines for migraine. The associations between falls and the number of psychoactive medicines used or the number of doses were analysed in comparison with falls that occurred when no psychoactive medicine was used. The adjusted results showed a significantly increased risk of falls when patients were on one or more psychoactive medicines or were receiving 0.1-0.9 defined daily dose (DDD) or more per day. The incident rate ratios (IRRs) were 1.22 (95% confidence interval [CI] 1.08-1.38) for those on one psychoactive medicine, 1.70 (95% CI 1.45-1.99) for those on two, 1.96 (95% CI 1.58-2.43) for those on three or four, and 3.15 (95% CI 1.90-5.23) for those on five or more. A similar result was observed when the data were analysed by dose, with the highest risk being found for those taking three or more DDD per day (adjusted IRR 4.26, 95% CI 2.75-6.58). Increased numbers or increased doses of psychoactive medicines are associated with an increased risk of hospitalization for falls in older adults. Strategies to reduce the psychoactive medicine burden are likely to translate into significant health benefits.
Towards the use of non-psychoactive cannabinoids for prostate cancer.

PubMed

Pacher, Pál

2013-01-01

The palliative effects of Cannabis sativa (marijuana), and its putative main active ingredient, Δ(9) -tetrahydrocannabinol (THC), which include appetite stimulation, attenuation of nausea and emesis associated with chemo- or radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer patients, are well-known. Because of the adverse psychoactive effects of THC, numerous recent preclinical studies have been focused on investigating other non-psychoactive constituents of C. sativa, such as cannabidiol, for potential therapeutic use. In this issue of the British Journal of Pharmacology, De Petrocellis and colleagues present comprehensive evidence that plant-derived cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma viability in vitro. They also showed that the extract was active in vivo, either alone or when administered with drugs commonly used to treat prostate cancer (the anti-mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti-androgen bicalutamide (Casodex)) and explored the potential mechanisms behind these antineoplastic effects. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
Fluorine in psychedelic phenethylamines.

PubMed

Trachsel, Daniel

2012-01-01

The so-called psychedelic phenethylamines represent a class of drugs with a large range of psychoactive properties in humans, ranging from naturally occurring mescaline to amphetamine analogues and homologues. The interest in many of these compounds, occasionally referred to as designer-drugs, is widely dispersed across popular culture and political and scientific communities. In recent decades, fluorine has become a powerful and important tool in medicinal chemistry. In addition, fluorine-containing compounds and medicines can be found in numerous commercially successful pharmaceuticals that have gained a market share of some 5-15%. One might anticipate this trend to increase in the future. As far as fluorinated phenethylamines are concerned, much less is known about their chemistry and pharmacology. This paper provides an overview regarding the biological properties of over 60 fluorinated phenethylamines and discusses both historical and recent chemistry-related developments. It was shown that the introduction of fluorine into the phenethylamine nucleus can impact greatly on psychoactivity of these compounds, ranging from marked loss to enhancement and prolongation of effects. For example, in contrast to the psychoactive escaline (70), it was observed that its fluoroescaline (76) counterpart was almost devoid of psychoactive effects. Difluoroescaline (77), on the other hand, retained, and trifluoroescaline (78) showed increased human potency of escaline (70). Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and duration of mescaline (22) effects. Copyright © 2012 John Wiley & Sons, Ltd.
Health Benefits of Methylxanthines in Cacao and Chocolate

PubMed Central

Franco, Rafael; Oñatibia-Astibia, Ainhoa; Martínez-Pinilla, Eva

2013-01-01

One may wonder why methylxanthines are so abundant in beverages used by humans for centuries, or in cola-drinks that have been heavily consumed since their appearance. It is likely that humans have stuck to any brew containing compounds with psychoactive properties, resulting in a better daily life, i.e., more efficient thinking, exploring, hunting, etc., however, without the serious side effects of drugs of abuse. The physiological effects of methylxanthines have been known for a long time and they are mainly mediated by the so-called adenosine receptors. Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food. The consequences of adenosine receptor blockade by natural compounds present in cacao/chocolate are here reviewed. Palatability and health benefits of methylxanthines, in general, and theobromine, in particular, have further contributed to sustain one of the most innocuous and pleasant habits: chocolate consumption. PMID:24145871
Synthetic cannabinoids: the hidden side of Spice drugs.

PubMed

Pintori, Nicholas; Loi, Barbara; Mereu, Maddalena

2017-09-01

Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs. The absence of validated testing procedures in the clinical field makes difficult the adoption of a therapeutic approach effective in coping with the synthetic cannabinoid phenomenon, posing a significant challenge for prevention, treatment and public health in general. The aim of this review is to gain insights into the epidemiological, pharmacological and toxicological properties of synthetic cannabinoids, aiming to provide a reliable background needed for the management of synthetic cannabinoid-related adverse effects. Consumers, competent authorities and medical care professionals should be aware of the risks associated with synthetic cannabinoid use.
Health benefits of methylxanthines in cacao and chocolate.

PubMed

Franco, Rafael; Oñatibia-Astibia, Ainhoa; Martínez-Pinilla, Eva

2013-10-18

One may wonder why methylxanthines are so abundant in beverages used by humans for centuries, or in cola-drinks that have been heavily consumed since their appearance. It is likely that humans have stuck to any brew containing compounds with psychoactive properties, resulting in a better daily life, i.e., more efficient thinking, exploring, hunting, etc., however, without the serious side effects of drugs of abuse. The physiological effects of methylxanthines have been known for a long time and they are mainly mediated by the so-called adenosine receptors. Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food. The consequences of adenosine receptor blockade by natural compounds present in cacao/chocolate are here reviewed. Palatability and health benefits of methylxanthines, in general, and theobromine, in particular, have further contributed to sustain one of the most innocuous and pleasant habits: chocolate consumption.
Identification of phase I and II metabolites of the new designer drug α-pyrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).

PubMed

Paul, Michael; Bleicher, Sergej; Guber, Susanne; Ippisch, Josef; Polettini, Aldo; Schultis, Wolfgang

2015-11-01

Pyrrolidinophenones represent one emerging class of newly encountered drugs of abuse, also known as 'new psychoactive substances', with stimulating psychoactive effects. In this work, we report on the detection of the new designer drug α-pyrrolidinohexiophenone (α-PHP) and its phase I and II metabolites in a human urine sample of a drug abuser. Determination and structural elucidation of these metabolites have been achieved by liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). By tentative identification, the exact and approximate structures of 19 phase I metabolites and nine phase II glucuronides were elucidated. Major metabolic pathways revealed the reduction of the ß-keto moieties to their corresponding alcohols, didesalkylation of the pyrrolidine ring, hydroxylation and oxidation of the aliphatic side chain leading to n-hydroxy, aldehyde and carboxylate metabolites, and oxidation of the pyrrolidine ring to its lactam followed by ring cleavage and additional hydroxylation, reduction and oxidation steps and combinations thereof. The most abundant phase II metabolites were glucuronidated ß-keto-reduced alcohols. Besides the great number of metabolites detected in this sample, α-PHP is still one of the most abundant ions together with its ß-keto-reduced alcoholic dihydro metabolite. Monitoring of these metabolites in clinical and forensic toxicology may unambiguously prove the abuse of the new designer drug α-PHP. Copyright © 2015 John Wiley & Sons, Ltd.
An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

PubMed

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs

PubMed Central

Parrott, Andrew C.

2018-01-01

Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will show how they disrupt the same core psychobiological functions, so damaging well-being in similar ways. Every psychoactive drug causes mood states to fluctuate. Users feel better on-drug, then feel worse off-drug. The strength of these mood fluctuations is closely related to their addiction potential. Cyclical changes can occur with many other core psychobiological functions, such as information processing and psychomotor speed. Hence the list of drug-related impairments can include: homeostatic imbalance, HPA axis disruption, increased stress, altered sleep patterns, neurohormonal changes, modified brain rhythms, neurocognitive impairments, and greater psychiatric vulnerability. Similar patterns of deficit are found with older drugs such as cocaine, nicotine and cannabis, and newer substances such as 3,4-methylenedioxymethamphetamine (MDMA), mephedrone and spice. All psychoactive drugs damage human well-being through similar basic neuropsychobiological mechanisms. PMID:29533974
The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

PubMed

McAllister, Sean D; Soroceanu, Liliana; Desprez, Pierre-Yves

2015-06-01

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.
The antitumor activity of plant-derived non-psychoactive cannabinoids

PubMed Central

McAllister, Sean D.; Soroceanu, Liliana; Desprez, Pierre-Yves

2015-01-01

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer stem cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment. PMID:25916739
Vaccine-driven pharmacodynamic dissection and mitigation of Captagon psychoactivity

PubMed Central

Wenthur, Cody J; Zhou, Bin; Janda, Kim D

2017-01-01

SUMMARY PARAGRAPH Fenethylline, also known as Captagon, is a synthetic psychoactive stimulant that has recently been linked to substance use disorder and ‘pharmacoterrorism’ in the Middle East.1–4 Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it additionally incorporates a covalently-linked xanthine moiety into its parent structure.5,6 These independently-active pharmacophores are liberated during metabolism, resulting in a structurally-diverse chemical mixture being deployed to the central nervous system.7–9 Although fenethylline’s psychoactive properties have been reported to differ from other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects.10,11 Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate fenethylline’s psychoactivity and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacologic activity. We anticipate that DISSECTIV will be employed to expose unidentified active chemical species and illuminate pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples, and natural product extracts. PMID:28813419
Abuse of the over-the-counter antispasmodic butylscopolamine for the home synthesis of psychoactive scopolamine.

PubMed

Kummer, Sebastian; Rickert, Annette; Daldrup, Thomas; Mayatepek, Ertan

2016-07-01

We report on two patients who ingested psychoactive scopolamine that was synthesized at home from butylscopolamine (Buscopan®), which is available as over-the-counter antispasmodic in nearly 100 countries worldwide. Patient 1 presented with severe central anticholinergic toxidrome, while patient 2 suffered from minor symptoms. An empty blister of Buscopan® was found in the patients' home, but initially was not suspected to be causative for the observed central anticholinergic symptoms, as Buscopan® is not able to pass the blood-brain barrier in its native form. Only later, the information by third parties and a Google search helped to identify homemade scopolamine derived from Buscopan® as the responsible agent in these two cases. Retrospectively, scopolamine could be detected in serum and urine of both patients, while it was absent in one control after ingestion of native Buscopan®. Over-the-counter drugs can be used to synthesize psychoactives with means that are available in every household. Such knowledge can spread via social media and internet discussion boards long before appearing in medical literature. While typical clinical presentation often enables clinicians to adequately identify and treat specific toxidromes, these sources of information need to be increasingly taken into account by medical professionals for identification of its causative agent. This potential of Buscopan® might gain importance as an easily accessible source of psychoactive scopolamine. • Substances with central anticholinergic effects are known for their hallucinogenic potential and may be used as psychoactives. What is New: • The over-the-counter antispasmodic butylscopolamine (Buscopan®) can be abused to synthesize anticholinergic, psychoactive scopolamine at home with means that are available in every household.
Permissive Attitude Towards Drug Use, Life Satisfaction, and Continuous Drug Use Among Psychoactive Drug Users in Hong Kong.

PubMed

Cheung, N Wt; Cheung, Y W; Chen, X

2016-06-01

To examine the effects of a permissive attitude towards regular and occasional drug use, life satisfaction, self-esteem, depression, and other psychosocial variables in the drug use of psychoactive drug users. Psychosocial factors that might affect a permissive attitude towards regular / occasional drug use and life satisfaction were further explored. We analysed data of a sample of psychoactive drug users from a longitudinal survey of psychoactive drug abusers in Hong Kong who were interviewed at 6 time points at 6-month intervals between January 2009 and December 2011. Data of the second to the sixth time points were stacked into an individual time point structure. Random-effects probit regression analysis was performed to estimate the relative contribution of the independent variables to the binary dependent variable of drug use in the last 30 days. A permissive attitude towards drug use, life satisfaction, and depression at the concurrent time point, and self-esteem at the previous time point had direct effects on drug use in the last 30 days. Interestingly, permissiveness to occasional drug use was a stronger predictor of drug use than permissiveness to regular drug use. These 2 permissive attitude variables were affected by the belief that doing extreme things shows the vitality of young people (at concurrent time point), life satisfaction (at concurrent time point), and self-esteem (at concurrent and previous time points). Life satisfaction was affected by sense of uncertainty about the future (at concurrent time point), self-esteem (at concurrent time point), depression (at both concurrent and previous time points), and being stricken by stressful events (at previous time point). A number of psychosocial factors could affect the continuation or discontinuation of drug use, as well as the permissive attitude towards regular and occasional drug use, and life satisfaction. Implications of the findings for prevention and intervention work targeted at psychoactive drug users are discussed.
The Growing Problem of New Psychoactive Substances (NPS).

PubMed

Madras, Bertha K

The term "new psychoactive substances" (NPS) can be defined as individual drugs in pure form or in complex preparations that are not scheduled under the Single Convention on Narcotic Drugs (1961) or the Convention on Psychotropic Substances (1971). NPS may be categorized by chemical structure, by psychoactive properties, by biological targets, or by source (plant, synthetic, or combined). The emergence of hundreds of NPS in the past decade is challenging for public health and drug policies globally. The novelty of NPS, their ambiguous legal status, ability to evade toxicological tests, swift adaptation to legal restrictions, global Internet marketing, and scant public knowledge of their adverse effects are among the key drivers of this twenty-first century phenomenon. Multi-disciplinary research in areas of biology, epidemiology, prevention, and web analytics are needed to develop effective responses in a domain capable of overwhelming current international conventions and national drug control policies. Ultimately, research-guided prevention education will fortify societies against this tidal wave.
[Suicide under the influence of "magic mushrooms"].

PubMed

Müller, Katja; Püschel, Klaus; Iwersen-Bergmann, Stefanie

2013-01-01

Psilocybin/psilocin from so-called psychoactive mushrooms causes hallucinogenic effects. Especially for people with mental or psychiatric disorders ingestion of magic mushrooms may result in horror trips combined with the intention of self-destruction and suicidal thoughts. Automutilation after consumption of hallucinogenic mushrooms has already been described. Our case report demonstrates the suicide of a man by self-inflicted cut and stab injuries. A causal connection between suicidal behaviour and previous ingestion of psychoactive mushrooms is discussed.
Something New about Something Old: A 10-Year Follow-Up on Classical and New Psychoactive Tryptamines and Results of Analysis.

PubMed

Palma-Conesa, Álvaro José; Ventura, Mireia; Galindo, Liliana; Fonseca, Francina; Grifell, Marc; Quintana, Pol; Fornís, Iván; Gil, Cristina; Farré, Magí; Torrens, Marta

2017-01-01

New psychoactive tryptamines may be a public health risk since they intend to mimic the hallucinogenic effects of regulated psychoactive drugs. Few studies describe uses and clinical effects of unregulated new psychoactive tryptamines. This study aims (1) to explore the presence of tryptamines classified as NPS among the substances delivered for analysis to a harm-reduction organization; (2) to describe the substances found in the samples after analysis; and (3) to compare analytical results of regulated vs. non-regulated tryptamines. Samples delivered and analyzed by gas chromatography-mass spectrometry from 2006 to 2015 were included. A descriptive study of results was conducted. From 25,296 samples that were delivered, 436 were tryptamines; from these 232 (53.21%) were non-regulated. The most delivered non-regulated tryptamine was 4-AcO-DMT. A search of the PubMed database in July 2016 revealed that no studies in humans have ever been carried out with 4-AcO-DMT. Unregulated tryptamines likely contained one unadulterated substance (p ≤ 0.001). The number of samples submitted which contained tryptamines increased during the course of the study, with significant differences in client expectations vs. analysis results between the controlled and uncontrolled groups. There is a need for further research in order to prevent the potential health risks associated with their use.

Fetal effects of psychoactive drugs.

PubMed

Salisbury, Amy L; Ponder, Kathryn L; Padbury, James F; Lester, Barry M

2009-09-01

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.
[Psychoactive effects of 'legal high': About lysergic acid amide (LSA)].

PubMed

Ponté, Camille; Lapeyre-Mestre, Maryse

2017-10-01

Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance Centre, resulting in unintended psychic effects and led to a hospitalisation in 2 cases. Other cases of serious LSA intoxication are published, including a death. It is important to inform about the risks related to LSA consumption, a substance which is freely available and sometimes hidden behind various plant names. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
Two Perspectives on Psychoactive Drugs: Commentary on Wolfensberger (1994).

ERIC Educational Resources Information Center

Levitas, Andrew; And Others

1994-01-01

This commentary on a 1994 article by Wolfensberger on the current mental retardation scene, in which he describes prescription psychoactive drugs as health destroying and life destroying, criticizes Wolfensberger's comments on "psychoactive medications," noting "elementary errors,""apparently concocted figures," and…
[The use of saliva for exposure assessments on designer drugs among adolescents].

PubMed

Napierała, Marta; Tezyk, Artur; Piznal, Małgorzata; Bogusiewicz, Joanna; Florek, Ewa

2015-01-01

Drug use is one of the fundamental problems of the contemporary world. Due to the debilitating effects on physical and mental health and the possibility of impaired social functions, it is extremely important to assess exposure to psychoactive substances among high-risk groups. Taking into account characteristics of adolescence, one of them includes young people. To assess the exposure of young people to drugs, survey research is the most commonly use. To establish reliability of the information indicated by the students, toxicological studies could be a good manner. High-performance liquid chromatography coupled with mass spectrometry (LC-MS) is currently one of the most common techniques use for the detection and determination of psychoactive substances in biological material. In practice, an important issue in toxicological studies is the selection of a suitable biological material. Taking into account economic considerations and the method of sampling, the saliva is an increasingly used alternative material. The aim of this study was to assess the exposure of junior high school students on psychoactive substances--designer drugs, through the analysis of surveys and qualitative analysis of saliva taken from teenagers. It has been shown that surveys are a relatively quick and easy form of assessing the exposure of young people to psychoactive substances, but require verification through toxicological analysis of biological material for the presence of psychoactive substances for their reliability. Poznan secondary school students experimented with designer drugs at a similar level as respondents of nationwide survey from 2013.
Clinical relevance of cannabis tolerance and dependence.

PubMed

Jones, R T; Benowitz, N L; Herning, R I

1981-01-01

Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems.
Drug-Gut Microbiota Interactions: Implications for Neuropharmacology.

PubMed

Walsh, Jacinta; Griffin, Brendan T; Clarke, Gerard; Hyland, Niall P

2018-05-21

The fate and activity of drugs are frequently dictated not only by the host per se but also by the microorganisms present in the gastrointestinal tract. The gut microbiome is known to, both directly and indirectly, affect drug metabolism. More evidence now hints at the impact that drugs can have on the function and composition of the gut microbiome. Both microbiota-mediated alterations in drug metabolism and drug-mediated alterations in the gut microbiome can have beneficial or detrimental effects on the host. Greater insights into the mechanisms driving these reciprocal drug-gut microbiota interactions are needed, to guide the development of microbiome-targeted dietary or pharmacological interventions, with the potential to enhance drug efficacy or reduce drug side-effects. In this review, we explore the relationship between drugs and the gut microbiome, with a specific focus on potential mechanisms underpinning the drug-mediated alterations on the gut microbiome and the potential implications for psychoactive drugs. This article is protected by copyright. All rights reserved.
Monitoring of caffeine consumption effect on skin blood properties by diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Milanic, Matija; Marin, Ana; Stergar, Jost; Verdel, Nina; Majaron, Boris

2017-07-01

Caffeine is the most widely consumed psychoactive substance in the world. It affects many tissues and organs, in particular central nervous system, heart, and blood vessels. The effect of caffeine on vascular smooth muscle cells is an initial transient contraction followed by significant vasodilatation. In this study we investigate the use of diffuse reflectance spectroscopy (DRS) for monitoring of vascular changes in human skin induced by caffeine consumption. DRS spectra were recorded on volar sides of the forearms of ten healthy volunteers at time delays of 0, 30, 60, 120, and 180 minutes after consumption of caffeine, while one subject served as a negative control. Analytical diffusion approximation solutions for diffuse reflectance from three-layer structures were used to assess skin composition (e.g., dermal blood volume fraction and oxygen saturation) by fitting to experimental data. The results demonstrate that cutaneous vasodynamics induced by caffeine consumption can be monitored by DRS, while changes in the control subject not consuming caffeine were insignificant.
Novel Psychoactive Substances in Young Adults with and without Psychiatric Comorbidities

PubMed Central

Martinotti, Giovanni; Acciavatti, Tiziano; Signorelli, Maria Salvina; Bandini, Laura; Ciambrone, Paola; Aguglia, Andrea; Calò, Salvatore; Janiri, Luigi; di Giannantonio, Massimo

2014-01-01

Objective. Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. Methods. A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. Results. Alcohol consumption was more frequent in the healthy young population compared to age-matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003). Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001). Conclusions. The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary. PMID:25133182
[Profile of psychoactive substances consumption in workplace].

PubMed

Bœuf-Cazou, Olivia; Lapeyre-Mestre, Maryse; Niezborala, Michel; Montastruc, Jean-Louis

2011-01-01

The aim of this study was to identify profiles of psychoactive substances consumers among workers according to their professional characteristics. In 2006, 2213 workers participated in "Mode de Vie et Travail" (Drugs and Work) cross-sectional survey. Data were collected by a self-administered questionnaire concerning general and professional characteristics and the consumption of psychoactive substances (psychoactive drugs, tobacco, alcohol and cannabis) during the professional medical visit. We identified consumer profiles with a hierarchical ascendant classification as statistical method. We underlined five profiles associated with psychoactive substance consumption: (1) alcohol consumers in the workplace were sales engineers satisfied with their employment, (2) alcohol consumers after their work were not satisfied with their lives, (3) cannabis consumers were men professionally satisfied but suffering from job insecurity, (4) smokers were workers with professional responsibilities under time pressure, and finally (5) poly-consumers had strong professional constraints. This study guides occupational physicians on psychoactive substances consumption among a worker population. © 2011 Société Française de Pharmacologie et de Thérapeutique.
Next generation of novel psychoactive substances on the horizon - A complex problem to face.

PubMed

Zawilska, Jolanta B; Andrzejczak, Dariusz

2015-12-01

The last decade has seen a rapid and continuous growth in the availability and use of novel psychoactive substances (NPS) across the world. Although various products are labeled with warnings "not for human consumption", they are intended to mimic psychoactive effects of illicit drugs of abuse. Once some compounds become regulated, new analogues appear in order to satisfy consumers' demands and at the same time to avoid criminalization. This review presents updated information on the second generation of NPS, introduced as replacements of the already banned substances from this class, focusing on their pharmacological properties and metabolism, routes of administration, and effects in humans. Literature search, covering years 2013-2015, was performed using the following keywords alone or in combination: "novel psychoactive substances", "cathinones", "synthetic cannabinoids", "benzofurans", "phenethylamines", "2C-drugs", "NBOMe", "methoxetamine", "opioids", "toxicity", and "metabolism". More than 400 NPS have been reported in Europe, with 255 detected in 2012-2014. The most popular are synthetic cannabimimetics and psychostimulant cathinones; use of psychedelics and opioids is less common. Accumulating experimental and clinical data indicate that potential harms associated with the use of second generation NPS could be even more serious than those described for the already banned drugs. NPS are constantly emerging on the illicit drug market and represent an important health problem. A significant amount of research is needed in order to fully quantify both the short and long term effects of the second generation NPS, and their interaction with other drugs of abuse. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Effectiveness of brief interventions as part of the Screening, Brief Intervention and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances: a systematic review

PubMed Central

2014-01-01

Background The purpose of this systematic review is to assess the effectiveness of brief interventions (BIs) as part of the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances. Methods Bibliographic databases (including MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO to April 2012) and gray literature sources were searched. We included randomized controlled trials that opportunistically screened adolescents or adults and then provided a one-to-one, verbal BI to those at risk of substance-use harm. Of interest was the nonmedical use of psychoactive substances (for example, drugs prohibited by international law), excluding alcohol, nicotine, and caffeine. Interventions comprised four or fewer sessions and were compared with no/delayed intervention or provision of information only. Studies were assessed for bias using the Cochrane risk of bias tool. Results were synthesized narratively. Evidence was interpreted according to the GRADE framework. Results We identified 8,836 records. Of these, five studies met our inclusion criteria. Two studies compared BI with no BI, and three studies compared BI with information only. Studies varied in characteristics such as substances targeted, screening procedures, and BI administered. Outcomes were mostly reported by a single study, leading to limited or uncertain confidence in effect estimates. Conclusions Insufficient evidence exists as to whether BIs, as part of SBIRT, are effective or ineffective for reducing the use of, or harms associated with nonmedical use of, psychoactive substances when these interventions are administered to nontreatment-seeking, screen-detected populations. Updating this review with emerging evidence will be important. Trial registration CRD42012002414 PMID:24887418
Effectiveness of brief interventions as part of the Screening, Brief Intervention and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances: a systematic review.

PubMed

Young, Matthew M; Stevens, Adrienne; Galipeau, James; Pirie, Tyler; Garritty, Chantelle; Singh, Kavita; Yazdi, Fatemeh; Golfam, Mohammed; Pratt, Misty; Turner, Lucy; Porath-Waller, Amy; Arratoon, Cheryl; Haley, Nancy; Leslie, Karen; Reardon, Rhoda; Sproule, Beth; Grimshaw, Jeremy; Moher, David

2014-05-24

The purpose of this systematic review is to assess the effectiveness of brief interventions (BIs) as part of the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances. Bibliographic databases (including MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO to April 2012) and gray literature sources were searched. We included randomized controlled trials that opportunistically screened adolescents or adults and then provided a one-to-one, verbal BI to those at risk of substance-use harm. Of interest was the nonmedical use of psychoactive substances (for example, drugs prohibited by international law), excluding alcohol, nicotine, and caffeine. Interventions comprised four or fewer sessions and were compared with no/delayed intervention or provision of information only. Studies were assessed for bias using the Cochrane risk of bias tool. Results were synthesized narratively. Evidence was interpreted according to the GRADE framework. We identified 8,836 records. Of these, five studies met our inclusion criteria. Two studies compared BI with no BI, and three studies compared BI with information only. Studies varied in characteristics such as substances targeted, screening procedures, and BI administered. Outcomes were mostly reported by a single study, leading to limited or uncertain confidence in effect estimates. Insufficient evidence exists as to whether BIs, as part of SBIRT, are effective or ineffective for reducing the use of, or harms associated with nonmedical use of, psychoactive substances when these interventions are administered to nontreatment-seeking, screen-detected populations. Updating this review with emerging evidence will be important. CRD42012002414.
Prevalence of Psychoactive Drug Use among North Dakota Group Home Residents.

ERIC Educational Resources Information Center

Burd, Larry; And Others

1991-01-01

A survey of 809 persons with mental retardation residing in community settings in North Dakota found that 37 percent were using psychoactive medications. Excluding anticonvulsant medications, only 18 percent were receiving psychoactive medications. A total of 37 percent of the individuals receiving medications other than anticonvulsants did not…
Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice

PubMed Central

Busquets-Garcia, Arnau; Soria-Gómez, Edgar; Redon, Bastien; Mackenbach, Yarmo; Chaouloff, Francis; Varilh, Marjorie; Ferreira, Guillaume; Piazza, Pier-Vincenzo; Marsicano, Giovanni

2017-01-01

Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side-effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS. PMID:28220044
Synthetic Cannabinoids-Further Evidence Supporting the Relationship Between Cannabinoids and Psychosis.

PubMed

Fattore, Liana

2016-04-01

Consumption of synthetic mind-altering compounds, also known as "new psychoactive substances," is increasing globally at an alarming rate. Synthetic cannabinoids (SCs) are among the most commonly used new psychoactive substances. They are usually purchased as marijuana-like drugs, marketed as herbal blends and perceived as risk-free by inexperienced users. Yet, contrary to Δ(9)-tetrahydrocannabinol, SCs may lead to severe health consequences, including anxiety, tachycardia, hallucinations, violent behavior, and psychosis. This review focuses on the latest (2010-2015) evidence of psychotic symptoms induced by ingestion of products containing SCs. Reports suggesting that SCs may either exacerbate previously stable psychotic symptoms (in vulnerable individuals) or trigger new-onset psychosis (in individuals with no previous history of psychosis) are reviewed. Pharmacology and toxicology of these compounds are discussed, with particular reference to their psychoactive effects. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Fate of psychoactive compounds in wastewater treatment plant and the possibility of their degradation using aquatic plants.

PubMed

Mackuľak, Tomáš; Mosný, Michal; Škubák, Jaroslav; Grabic, Roman; Birošová, Lucia

2015-03-01

In this study we analyzed and characterized 29 psychoactive remedies, illicit drugs and their metabolites in single stages of wastewater treatment plants in the capital city of Slovakia. Psychoactive compounds were present within all stages, and tramadol was detected at a very high concentration (706 ng/L). Significant decreases of codeine, THC-COOH, cocaine and buprenorphine concentration were observed in the biological stage. Consequently, we were interested in the possibility of alternative tertiary post-treatment of effluent water with the following aquatic plants: Cabomba caroliniana, Limnophila sessiliflora, Egeria najas and Iris pseudacorus. The most effective plant for tertiary cleansing was I. pseudacorus which demonstrated the best pharmaceutical removal capacity. After 48 h codeine and citalopram was removed with 87% efficiency. After 96 h were all analyzed compounds were eliminated with efficiencies above 58%. Copyright © 2015 Elsevier B.V. All rights reserved.
Sex bias in psychoactive drug advertisements.

PubMed

King, E

1980-05-01

A recent concern has been the possible effect of sex-role stereotypes upon physicians' prescription patterns. In an attempt to examine the part played by drug advertisements, this paper will present a content analysis of psychoactive (mood-modifying) drug ads appearing in the American Journal of Psychiatry over a 17-year period; and a study of subjects' perceptions of the patients depicted in these drug ads across eight dimensions emerging from the content analysis. An initial perusal of psychoactive drug ads in professional medical journals suggested the existence of a sex bias: Females appeared to be presented as patients more often than males, and in a much more demeaning manner. The present analyses were done in an attempt to discover if a sex bias does exist in drug advertisements, which may influence the physician's perception of his or her patients, and subsequently, his or her prescription patterns.
Implications of psychoactive 'bath salts' use during pregnancy.

PubMed

Gray, Bobbe Ann; Holland, Cindra

2014-01-01

Psychoactive bath salts (PABS) comprise a group of highly dangerous designer drugs showing a sharp escalation in reported U.S. exposures from 2010 through 2012, following rapid spread of the drug in Europe. Since a federal ban on the major ingredients in October 2011, numbers have declined. However, evidence from the United Kingdom shows an initial decline after the UK ban in 2010 with a 400 percent increase in reports by 2012. Actual information about the effect of PABS use on pregnant women and fetuses is almost nonexistent. Clinicians should be aware of the potential maternal, fetal and neonatal effects of PABS. © 2014 AWHONN.
[Designer drugs and caffeine - characteristics of psychoactive substances and their impact on the organism].

PubMed

Wierzejska, Regina

2014-01-01

For many teenagers the time of growing up is a period of trying prohibited substances. Nowadays apart from alcohol and tobacco new designed, psychoactive substances known as "smart drugs" or "legal highs" are available. Intensive development of their market is taking place in the last few years which is difficult to overcome by regulations only. Toxicological tests used now are not able to detect the presence of many such substances in the body. Designer drugs cause the interest of young people even from small towns and many times taking them give effects requiring medical help. Caffeine is also a psychoactive substance but depending on the dose it can have positive or detrimental effect. Recently there are more and more products with caffeine, especially drinks and dietary supplements, what can cause the increase of consumption of caffeine. Children are particularly exposed to the adverse effect of high consumption of caffeine because of their small body weight and development of the central nervous system. This article presents actual data about the market of designer drugs, frequency of using them, consumption of caffeine by children and teenagers and about the impact of these substances on the organism.
Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.

PubMed

Carod-Artal, F J

2015-01-01

The American continent is very rich in psychoactive plants and fungi, and many pre-Columbian Mesoamerican cultures used them for magical, therapeutic and religious purposes. The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp contains bufotoxins with hallucinogenic properties, and was used since the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

PubMed

Jacob, Michael S; Presti, David E

2005-01-01

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.
Factors associated with psychoactive drug initiation in a sample of workers in France: results of the VISAT cohort study.

PubMed

Boeuf-Cazou, O; Niezborala, M; Marquie, J C; Lapeyre-Mestre, M

2010-03-01

To identify which psychosocial factors at work are associated with the initiation of psychoactive drug use in a cohort of healthy French workers. This study used data collected from the VISAT ('Vieillissement, Santé, Travail') cohort which included workers aged 32, 42, 52 and 62 years in 1996 with follow-ups conducted over the following 5 years. Data were collected through interviews and five standardized questionnaires in annual occupational medical examinations in 1996, 1999 and 2001. We defined new consumers of psychoactive drugs according to their answers during the follow-ups and compared their psychosocial and working characteristics to non-consumers. A multivariate logistic regression analysis was performed to investigate factors related to a psychoactive drug initiation. Among 1533 subjects, 5.4% began consuming psychoactive drugs during the follow-up with a twofold rate for women than for men. Factors related to psychoactive drug initiation were different according to gender. In men, initiation was mainly found in participants who were separated, showed high emotional reaction scores and were members of the white-collar working class. We did not find any other occupational factors associated to psychoactive drug initiation in men. By contrast, among women, drug initiation was more frequent in participants who were 52 years old and over, and whose job control-reward level was lower. Psychoactive drug initiation concerned 5.4% of workers within the 5-year interval in this study. The pressure of psychosocial environment was more important in men, whereas age and work-related psychosocial factors were the main factors associated with new consumption among women.
Early detection of emerging street drugs by near infrared spectroscopy and chemometrics.

PubMed

Risoluti, R; Materazzi, S; Gregori, A; Ripani, L

2016-06-01

Near-infrared spectroscopy (NIRs) is spreading as the tool of choice for fast and non-destructive analysis and detection of different compounds in complex matrices. This paper investigated the feasibility of using near infrared (NIR) spectroscopy coupled to chemometrics calibration to detect new psychoactive substances in street samples. The capabilities of this approach in forensic chemistry were assessed in the determination of new molecules appeared in the illicit market and often claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects. The study focused on synthetic molecules belonging to the classes of synthetic cannabinoids and phenethylamines. The approach was validated comparing results with officials methods and has been successfully applied for "in site" determination of illicit drugs in confiscated real samples, in cooperation with the Scientific Investigation Department (Carabinieri-RIS) of Rome. The achieved results allow to consider NIR spectroscopy analysis followed by chemometrics as a fast, cost-effective and useful tool for the preliminary determination of new psychoactive substances in forensic science. Copyright © 2016 Elsevier B.V. All rights reserved.
Opioids in the Frame of New Psychoactive Substances Network: A Complex Pharmacological and Toxicological Issue.

PubMed

Ventura, Ludovic; Carvalho, Felix; Dinis-Oliveira, Ricardo Jorge

2018-01-01

New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS. Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin. Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
[Prevalence of psychoactive drug consumption in an obese population].

PubMed

Cerdá Esteve, Maria A; Barral Tafalla, Diego; Gudelis, Mindaugas; Goday, Albert; Farre Albaladejo, Magi; Cano, Juan F

2010-04-01

To establish the prevalence of psychoactive drug consumption in an obese population. We collected data from the clinical records of obese patients attending the Endocrinology and Nutrition Department and Psychiatry Department of Hospital del Mar between June 2005 and May 2006 (n=259). We recorded anthropometric, epidemiological and toxicological data. We also investigated the prevalence of concomitant diseases in this population. Psychoactive drugs were consumed by 37% of obese patients, mainly antidepressants (27%), anxiolytics, sedatives and hypnotics, and anticonvulsants. Moreover, 15% of all patients received combination treatment with two or more psychoactive drugs, mostly the association of an antidepressant and an antiepileptic drug. The prevalence of psychoactive drug consumption in our sample was higher than prevalence data observed in the general population, with antidepressant consumption being three-fold higher. Copyright 2009 SEEN. Published by Elsevier Espana. All rights reserved.
Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder

PubMed Central

Harch, Paul G.; Andrews, Susan R.; Fogarty, Edward F.; Lucarini, Juliette; Van Meter, Keith W.

2017-01-01

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18–65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle ear barotrauma (n = 6), transient deterioration in symptoms (n = 7), reversible bronchospasm (n = 1), and increased anxiety (n = 2; not related to confinement); unrelated to HBOT: ureterolithiasis (n = 1), chest pain (n = 2). Significant improvement (29 subjects) was seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexterity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects' SPECT was significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in 75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced a significant reduction in suicidal ideation and reduction in psychoactive medication use. PMID:29152209
Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder.

PubMed

Harch, Paul G; Andrews, Susan R; Fogarty, Edward F; Lucarini, Juliette; Van Meter, Keith W

2017-01-01

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle ear barotrauma ( n = 6), transient deterioration in symptoms ( n = 7), reversible bronchospasm ( n = 1), and increased anxiety ( n = 2; not related to confinement); unrelated to HBOT: ureterolithiasis ( n = 1), chest pain ( n = 2). Significant improvement (29 subjects) was seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexterity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects' SPECT was significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in 75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced a significant reduction in suicidal ideation and reduction in psychoactive medication use.
[New psychoactive substances abuse among patients with access to methadone maintenance treatment in Jiangsu province: a case-control study].

PubMed

Cheng, Z; Chen, G H; Dai, M M; Luo, W; Lyu, P; Cao, X B

2018-05-10

Objective: To explore the reasons and factors associated with new psychoactive substances abuse among patients with access to methadone maintenance treatment (MMT). Methods: A well-developed questionnaire and urine tests were used to collect information about demographic characteristics, condition of MMT and drug abuse, family and social support of MMT clients. A 1∶1 matched case-control study was conducted, and conditional logistic regression model was used to identify factors associated with new psychoactive substances abuse. Results: A total of 212 (106 pairs) clients receiving MMT were recruited, and most of them were males (78.3 % , 166/212), married or cohabitant (48.6 % , 103/212) and unemployed (63.2 % , 134/212). The average age of the clients was (45.1±7.2) years. The main types of abused new psychoactive substances were benzodiazepine (62.3 % , 66/106) and methamphetamine (39.6 % , 42/106). The proportion of abusing multi new psychoactive substances was 8.5 % (9/106). Results from multivariate conditional logistic regression analysis indicated that using opioid drug during the past 6 months of MMT treatment might increase the risk of abusing new psychoactive substances ( OR =3.25, 95 %CI : 1.35-7.79), benzodiazepine ( OR =3.25, 95 %CI : 1.11- 9.47) and methamphetamine ( OR =13.31, 95 %CI : 1.12-158.01). Moreover, MMT for more than9 years reduced the risk of abuse of new psychoactive substances ( OR =0.03, 95 %CI : 0.01-0.21), benzodiazepine ( OR =0.02, 95 %CI : 0.00-0.36) and methamphetamine ( OR =0.02, 95 %CI : 0.00-0.69). Conclusion: Less new psychoactive substances abuse might be associated with longer duration of MMT treatment. And inappropriate support from family and friends might increase the risk of abusing new psychoactive substances in MMT clients, especially in clients who used opioid.
Psychoactive drug consumption: performance-enhancing behaviour and pharmacodependence in workers.

PubMed

Ngoundo-Mbongue, T B; Niezborala, M; Sulem, P; Briant-Vincens, D; Bancarel, Y; Jansou, P; Chastan, E; Montastruc, J L; Lapeyre-Mestre, M

2005-02-01

The aim of this study was to investigate factors associated to psychoactive medication use and dependence in working environment during a 1-year period. We performed a 1-year-follow-up cohort study including workers from Toulouse metropolitan area. During their annual compulsory examination to assess their aptitude to work, subjects were asked to fill in an anonymous questionnaire at 1 year interval, in May 2000 and May-June 2001. Among a study sample of 1273 subjects (47.4% of men, mean age 39.2 +/- 9.2 years), the prevalence of psychoactive medication use at baseline was 9.1% (4.3% anxiolytic, 1.9% hypnotic, 1.7% antidepressant, 2.1% opiate analgesic and 0.5% antipsychotic drugs, according to ATC classification). Dependence on these drugs was found in 3.5% of workers. This consumption was associated with professional categories (higher in employees versus senior executive, Odds Ratio: 1.80; 95% Confidence Interval [1.04-3.11]), low job satisfaction and outside workplace (1.92; [1.30-2.84] and 3.40; [2.27-5.09] respectively), and patterns of medication use at workplace: for sleeping disorders related to job (18.27; [11.81-28.26]), for enhancing performance at work (28.13; [12.00-65.92]), for relieving unpleasant symptoms at work (22.98; [9.59-55.01]). The risk of psychoactive medication chronic use (psychoactive drug users in 2000 and 2001), and dependence at 1 year were both strongly associated with nicotine dependence (5.99 and 6.23, respectively) and performance-enhancing behaviour with drugs and/or alcohol (8.35 and 3.32 respectively), whereas current use (psychoactive drug users only in 2001) was strongly associated with performance-enhancing behaviour. Among workers using psychoactive drugs, one out of three are dependent on psychoactive medications. Performance-enhancing behaviour and coping strategies might be a determinant of psychoactive drug use and could lead to dependence in the workplace.
Psychoactive substances use and associated factors among middle and high school students in the North Center of Morocco: a cross-sectional questionnaire survey.

PubMed

Zarrouq, B; Bendaou, B; El Asri, A; Achour, S; Rammouz, I; Aalouane, R; Lyoussi, B; Khelafa, S; Bout, A; Berhili, N; Hlal, H; Najdi, A; Nejjari, C; El Rhazi, K

2016-06-04

Data on psychoactive substance (PAS) consumption among adolescents in the North Center of Morocco are not at all available. Therefore, the current study aimed at investigating the prevalence and the determinants of psychoactive substances use among middle and high school students in this region. A cross-sectional study was conducted from April 2012 to November 2013 in public middle and high schools in the North Central Region of Morocco. An anonymous self-administered questionnaire was used to assess psychoactive substances use among a representative sample of school students from the 7th to the 12th grade, aged 11-23 years, selected by stratified cluster random sampling. Factors associated with psychoactive substance use were identified using multivariate stepwise logistic regression analyses. A total of 3020 school students completed the questionnaires, 53.0 % of which were males. The overall lifetime smoking prevalence was 16.1 %. The lifetime, annual and past month rates of any psychoactive substance use among the study subjects were 9.3, 7.5, and 6.3 % respectively. Cannabis recorded the highest lifetime prevalence of 8.1 %, followed by alcohol 4.3 %, inhalants 1.7 %, psychotropic substances without medical prescription 1.0, cocaine 0.7, heroine 0.3, and amphetamine with only 0.2 %. Psychoactive substance use was associated with males more than females. The risk factors identified by multivariate stepwise logistic regression analyses were being male, studying in secondary school level, smoking tobacco, living with a family member who uses tobacco, and feeling insecure within the family. The prevalence among all school students reported by the current study was comparable to the national prevalence. Efforts to initiate psychoactive substance prevention programs among school students should be made by designing such programs based on the significant factors associated with psychoactive substance use identified in this study.
[Prevalence and predictors of psychoactive substance use among men in prisons].

PubMed

Caravaca-Sánchez, Francisco; Falcón Romero, María; Luna, Aurelio

2015-01-01

The use of psychoactive substances among the prison population is an important public health issue because of its magnitude and health consequences. The aim of this study was to estimate the prevalence of psychoactive substance use among the prison population and to analyse its association with sociodemographic and penitentiary factors, particularly the size of the prison. Data were gathered using a self-administered questionnaire among 2,484 random male inmates in eight prisons of different sizes in Spain. The prevalence of psychoactive substance use with 95% confidence intervals (95% CI) during the last 6 months in prison were estimated. Prevalence ratios were used to estimate the association between psychoactive substance use and sociodemographic and penitentiary characteristics. The prevalence of psychoactive substance use in the past 6 months in prison was 59.9% (95% CI: 57.9-62.0). Notable among the sociodemographic variables associated with substance use were drug consumption prior to imprisonment (6.90; 95% CI: 5.51-8.65) and recidivism in prison (2.41; 95% CI: 2.04-2.85). The largest prisons showed a higher frequency of drug use than other prisons. A high prevalence of psychoactive substance use was found in prisons and significant differences were found according to delinquent profile and the size of the prison. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.
[Salivary flow and psychoactive drug consumption in elderly people].

PubMed

Cabrera, Marcos Aparecido Sarria; Mesas, Arthur Eumann; Rossato, Luiz Angelo; Andrade, Selma Maffei de

2007-01-01

To analyze the association between low saliva flow rates and the use of psychoactive drugs among the elderly. A cross-sectional study was carried out with 267 elderly people from 60 to 74 years of age who lived in a borough of the city of Londrina, Paraná State, Brazil. Individuals with high functional dependence or restricted to bed were excluded. Saliva flow rate was the dependent variable with values under the first tercile being considered as low flow rates (less than 0.44 ml/min). The continuous use of psychoactive drugs (antidepressant, antiepileptic, sedative, antipsychotic, hypnotic or sedative-hypnotic drugs) was the independent variable. Multivariate analysis was performed taking into account gender, age and smoking status. The majority of the elderly were women (80.5%), with a mean age of 66.5 years. Use of psychoactive drugs was observed among 31 elderly (11.6%). Mean saliva flow rate was 0.76 ml/min, lower among users of psychoactive drugs (0.67 ml/min). In the multivariate analysis, use of psychoactive drugs was associated with low saliva flow rates (<0.44 ml/min), independent of gender, age or smoking. Results show that there is an association between use of psychoactive drugs and low saliva flow rates in this group of independent and non-institutionalized elderly. These conclusions stress the need of a rational use of these drugs, particularly among the elderly.
Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments.

PubMed

Renard, Justine; Norris, Christopher; Rushlow, Walter; Laviolette, Steven R

2017-04-01

Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders. In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties. However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties. Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties. This review summarizes clinical and pre-clinical evidence demonstrating CBD's modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT 1A receptor system, and their downstream molecular signaling effects. Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.
Prevalence of psychoactive substance use among commercial motorcyclists and its health and social consequences in Zaria, Nigeria.

PubMed

Alti-Muazu, M; Aliyu, A A

2008-06-01

In recent years commercial motorcyclists (Okada riders) have come to bridge the huge public transport gap in most cities across the country. However, this is not without the dangers they pose to themselves, passengers and to other road users. It is claimed that some of these Okada riders operate under the influence of drugs and other substances. But there are few community-based studies that have investigated the problem in this part of Nigeria. Therefore, this study was conducted to determine the prevalence, health and social consequences of psychoactive substance use among commercial motorcyclists (Okada) in Zaria, northern Nigeria. Multi-stage sampling technique was used to sample commercial motorcyclists registered with commercial motorcyclists union in Zaria city, Kaduna state, Nigeria. Structured, closed ended and interviewer administered questionnaires were used to collect information on socio-demographic characteristics, factors influencing psychoactive substance use, impact on health status, motor cycle riding experience and work performance. Two hundred commercial motor cyclists were intervi ewed, majority of them were in the age group 21-25 years (55.5%) with a mean age of 25.4 +/- 3.9 years. All the motorcyclists were male, (60.5%), had no formal education, (79.5%) are of Hausa extraction and (69%) worked for more than 10 hours per day. A high prevalence of 59.5% of road traffic accident that was associated with the use of psychoactive drugs was found among the motorcyclists. Commonly identified psychoactive substance/drugs used were: marijuana [Indian hemp] 25.8%, solution 24.5%, caffeine (Kola) 15.8%, and coffee 4.8%. Keeping awake, suppression of fatigue, and peer group effect were the identified factors influencing psychoactive substance use. The commonest types of injuries sustained were bruises and lacerations (62.5%) and fractures of upper and lower limbs (10.5%). Road traffic accidents among commercial motorcyclists are a frequent occurrence in this part of the country. There is need for public awareness campaigns on road safety education and health consequences of psychoactive substance use among commercial motorcyclists. It is further recommended that law enforcement agencies (NAFDAC, NDLEA and FRSC) need to work in tandem so as to curb the problem of substance abuse in our society and reduce the rate of accidents on Nigerian roads.
A systematic review of the effects of novel psychoactive substances 'legal highs' on people with severe mental illness.

PubMed

Gray, R; Bressington, D; Hughes, E; Ivanecka, A

2016-06-01

WHAT IS KNOWN ON THE SUBJECT?: Novel psychoactive substances (NPS) include synthetic drugs mimicking the effects of illicit drugs, e.g. synthetic cannabinoids, and herbs such as Salvia divinorum. NPS are substances that can trigger hallucinations and other effects altering the mind, and are currently uncontrolled by the United Nations' 1961 Narcotic Drugs/1971 Psychotropic Substances Conventions. NPS affect brain chemistry that induces the psychoactive effects, such as hallucinations and feeling 'high'. It is unknown what effects such drugs have on people with severe mental illness (i.e. psychotic illnesses). WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Our review demonstrates that little is known about the effects of various NPS on people with severe mental illness. Almost nothing is known about the long-term consequences of NPS use on the mental and physical health of SMI patients. Patients may lack understanding that NPS are psychoactive drugs that can impact on their mental and physical wellbeing. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Some patients might be reluctant or do not think it is relevant to disclose NPS use. Commonly used illicit drug screening is unlikely to detect the presence of NPS, therefore health and mental health professionals should directly enquire about NPS and actively encourage patients with severe mental illness to disclose any substance use. There was no significant patient and public involvement in the development and conduct of this study . Introduction Novel psychoactive substances (NPS) are synthetic substances that have been developed to produce altered states of consciousness and perceptions. People with severe mental illness (SMI) are more likely to use NPS than people without mental illness, but the short- and long-term effects of NPS are largely unknown. Method We systematically reviewed the literature about the effects of NPS on people with SMI. Results We included 12 case reports, 1 cross-sectional survey and 1 qualitative study. Participants included mostly males aged between 20 and 35 years. A variety of NPS were used, including synthetic cathinones and herbs such as Salvia. The most commonly reported effects of NPS were psychotic symptoms (in some cases novel in form and content to the patients' usual symptoms) and significant changes in behaviour, including agitation, aggression and violence. Patients' vital signs, such as blood pressure, pulse rate and temperature, were also commonly affected. Conclusion NPS potentially have serious effects on people with SMI, but our findings have limited generalizability due to a reliance on case studies. There is a paucity of evidence about the long-term effects of these substances. Further research is required to provide a better understanding about how different NPS affect patients' mental and physical health. © 2016 John Wiley & Sons Ltd.
Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand.

PubMed

Rychert, Marta; Wilkins, Chris; Witten, Karen

2017-09-01

New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for 'low risk' psychoactive products ('legal highs'). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Semi-structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. The selection of 'safer' products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.
Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Abe, Kohji; Hasebe, Nobuyoshi; Takamatsu, Fumie; Yasuda, Hiromi; Ikeda, Tomoaki; Inui, Keiichiro; Egashira, Nobuaki; Iwasaki, Katsunori; Fujiwara, Michihiro

2004-10-25

Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.
Managing misuse of novel psychoactive substances.

PubMed

Solomon, David; Grewal, Pardeep; Taylor, Chloe; Solomon, Bernadette

Misuse of novel psychoactive substances, also known as legal highs, is growing in the UK. These substances include more than 200 psychoactive chemicals and are associated with harm to physical and mental health, but are not controlled under the Misuse of Drugs Act 1971 or regulated as a medicine. This article reviews the evidence relating to psychosocial interventions for illegal substance misuse to identify how therapies could improve rates of abstinence and awareness in adults who are misusing novel psychoactive substances. The evidence is limited and there is a need for further research and increased awareness among health professionals and the general population of this growing problem.
Lifestyle use of drugs by healthy people for enhancing cognition, creativity, motivation and pleasure.

PubMed

d'Angelo, L-S Camilla; Savulich, George; Sahakian, Barbara J

2017-10-01

Today, there is continued, and in some cases growing, availability of not only psychoactive substances, including treatments for mental health disorders such as cognitive enhancers, which can enhance or restore brain function, but also 'recreational' drugs such as novel psychoactive substances (NPS). The use of psychoactive drugs has both benefits and risks: whilst new drugs to treat cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have great benefits for many patient groups, the increasing ease of accessibility to recreational NPS and the increasing lifestyle use of cognitive enhancers by healthy people means that the effective management of psychoactive substances will be an issue of increasing importance. Clearly, the potential benefits of cognitive enhancers are large and increasingly relevant, particularly as the population ages, and for this reason, we should continue to devote resources to the development of cognitive enhancers as treatments for neurodegenerative diseases and psychiatric disorders, including Alzheimer's disease, attention deficit hyperactivity disorder and schizophrenia. However, the increasing use of cognitive enhancers by healthy individuals raises safety, ethical and regulatory concerns, which should not be ignored. Similarly, understanding the short- and long-term consequences of the use of NPS, as well as better understanding the motivations and profiles of users could promote more effective prevention and harm reduction measures. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.
Understanding the risks associated with the use of new psychoactive substances (NPS): high variability of active ingredients concentration, mislabelled preparations, multiple psychoactive substances in single products.

PubMed

Zamengo, Luca; Frison, Giampietro; Bettin, Chiara; Sciarrone, Rocco

2014-08-17

New psychoactive substances (NPS), are now a large group of substances of abuse not yet completely controlled by international drug conventions, which may pose a public health threat. Anxiety, paranoia, hallucinations, seizures, hyperthermia and cardiotoxicity are some of the common adverse effects associated with these compounds. In this paper, three case reports taken from the archive of processed cases of the authors' laboratory are presented and discussed to stress the risks of possible adverse consequences for NPS users: in particular, (i) the risk deriving from the difficulty of predicting the actual consumed dose, due to variability of active ingredients concentration in consumed products, (ii) the risk deriving from the difficulty of predicting the actual active ingredients present in consumed products, as opposed to those claimed by the manufacturer, and (iii) the risk deriving from the difficulty of predicting the actual pharmacological and toxicological effects related to the simultaneous consumption of different psychoactive ingredients contained in single products, whose interactions are mostly unknown. Each of them individually provide a source of concern for possible serious health related consequences. However, they should be considered in conjunction with each others, with the worldwide availability of NPS through the web and also with the incessantly growing business derived from the manipulation and synthesis of new substances. The resulting scenario is that of a cultural challenge which demands a global approach from different fields of knowledge. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Psycho-active substance use among in-school adolescents in Zaria, north western Nigeria: what are the triggers?

PubMed

Idris, S H; Sambo, M N

2009-01-01

Psycho-active substances have been used by various societies since the dawn of civilization, and still remain a major public health concern in the 21st century. Evidence has shown that in the last 2 decades in Nigeria, adolescents are a major group involved in the use of psychoactive substances. The study was carried out to determine pattern of use and the push factors for such use among in school adolescents in Zaria, Nigeria. The study was cross sectional descriptive in design. A multi-stage sampling technique was used to interview 280 respondents using self administered, structured and pre tested questionnaires. Data was analyzed manually and chi-square test statistic was used to test for significance of association between categorical variables at p value of < 0.05. A total of 280 respondents, 195 (69.6%) males and 85 (30.4%) females senior secondary school adolescent were interviewed. The study shows that 157 (56%) use one or more substance or the other. The commonest ones are kola nut followed by cigarette and marijuana. The commonest push factor for use is to experiment (54%). The study also shows, statistically significant relationship between family background and psychoactive substance use (chi2 = 21.57, df = 2 p < 0.05), there was however no statistical significance between age, class of the students and substance use respectively (chi2 = 1.94, df = 2 p > 0.05) (chi2 = 0.97, df = 2p > 0.05). The prevalence of psychoactive substances use is unacceptably high and the main trigger identified was the process of experimentation in order to discover their effects. There is the need to institutionalize preventive strategies against substance abuse in our secondary schools. Further studies in this area are also recommended.
Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

PubMed

Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

2017-05-01

Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.
Maintenance of Blinding in Clinical Trials and the Implications for Studying Analgesia Using Cannabinoids

PubMed Central

Wilsey, Barth; Deutsch, Reena; Marcotte, Thomas D.

2016-01-01

Abstract The design of analgesic clinical trials invariably involves a comparison between placebo and active study medication. An assumption is made that treatment effects can be approximated by subtracting the response to placebo from that attained with the use of active study medication. However, the psychoactivity of cannabinoids may unmask their presence and lead to an expectation and/or conditioning of pain relief. For example, study participants biased toward the belief that cannabis is beneficial for their condition might be more inclined to report positive effects if they were to accurately identify the active treatment because of its psychoactivity. This may lead to incorrect assumptions regarding the efficacy of a cannabinoid. Methodologies designed to counteract unmasking need to be implemented in the design phase of a study. During the clinical trial, it is also important to query participants as to which treatment they believe they have received. Blinding can be considered to be preserved when the accuracy of treatment guesses is not considerably different than random guessing, which is estimated to be correct 50% of the time. After a study has been completed, the use of statistical methodologies such as regression and mediation analysis are worthy of consideration to see whether psychoactive effects biased the results. PMID:28861490
Portugal's 2001 Drugs Liberalisation Policy: A UK Service Provider's Perspective on the Psychoactive Substances Act (2016)

ERIC Educational Resources Information Center

Banbury, Samantha; Lusher, Joanne; Guedelha, Francisco

2018-01-01

The Misuse of Drugs Act (1971) and the Psychoactive Substances Act (2016) both reinforce the criminalisation of drug use in the UK. The Psychoactive Substances Act (2016) has been developed to control and monitor the use of legal highs, particularly in institutions. This study aimed to establish drug service providers' viewpoints on how effective…
Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR).

PubMed

McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V; Power, John D; Twamley, Brendan; O'Brien, John; Talbot, Brian; Dowling, Geraldine; Mahony, Olivia; Brandt, Simon D; Patrick, Julian; Archer, Roland P; Partilla, John S; Baumann, Michael H

2015-07-01

The recent occurrence of deaths associated with the psychostimulant cis-4,4'-dimethylaminorex (4,4'-DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4-methylenedioxy-4-methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis- and trans-MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis-isomer (90%). Exposure of the cis-isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans-isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non-selective monoamine releasing agent (+)-3,4-methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis- and trans-4,4'-DMAR, were assessed under identical conditions. cis-MDMAR, trans-MDMAR, cis-4,4'-DMAR and trans-4,4'-DMAR were more potent than MDMA in their ability to function as efficacious substrate-type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis-4,4'-DMAR, cis-MDMAR and trans-MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans-4,4'-DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring-substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side-effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd.
Medical marijuana programs - Why might they matter for public health and why should we better understand their impacts?

PubMed

Fischer, Benedikt; Murphy, Yoko; Kurdyak, Paul; Goldner, Elliot; Rehm, Jürgen

2015-01-01

Although cannabis is an illegal drug, 'medical marijuana programs' (MMPs) have proliferated (e.g., in Canada and several US states), allowing for legal cannabis use for therapeutic purposes. While both health risks and potential therapeutic benefits for cannabis use have been documented, potential public health impacts of MMPs - also vis-à-vis other psychoactive substance use - remain under-explored. We briefly reviewed the emerging evidence on MMP participants' health status, and specifically other psychoactive substance use behaviors and outcomes. While data are limited in amount and quality, MMP participants report improvements in overall health status, and specifically reductions in levels of risky alcohol, prescription drug and - to some extent - tobacco or other illicit drug use; at the same time, increases in cannabis use and risk/problem patterns may occur. MMP participation may positively impact - for example, by way of possible 'substitution effects' from cannabis use - other psychoactive substance use and risk patterns at a scale relevant for public health, also influenced by the increasing population coverage of MMPs. Yet, net overall MMP-related population health effects need to be more rigorously and comprehensively assessed, including potential increases in cannabis use related risks and harms.
Update on administration of anesthetics and psychoactive drugs for pain management in China.

PubMed

Gu, Weiping

2015-06-01

Anesthetics and psychoactive drugs could relieve diseases, if used properly. However, they can cause dependency, and their misuse or abuse could adversely affect people's health and social stability. For a long time, the Chinese government has been reinforcing the regulation on anesthetics and psychoactive drugs to ensure their legal and proper usage, and to prevent abuse. The state council issued 'the regulations on the administration of anesthetic drugs and psychotropic drugs' in 2005, based on which a legal system was established for administration of anesthetics and psychoactive drugs with the objectives of ensuring their legitimate medical utilization, and preventing illegal abuse. Copyright © 2015. Published by Elsevier B.V.
Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2016-01-01

Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.
Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens.

PubMed

Rickli, Anna; Moning, Olivier D; Hoener, Marius C; Liechti, Matthias E

2016-08-01

The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
Episodic Memories and Their Relevance for Psychoactive Drug Use and Addiction

PubMed Central

Müller, Christian P.

2013-01-01

The majority of adult people in western societies regularly consume psychoactive drugs. While this consumption is integrated in everyday life activities and controlled in most consumers, it may escalate and result in drug addiction. Non-addicted drug use requires the systematic establishment of highly organized behaviors, such as drug-seeking and -taking. While a significant role for classical and instrumental learning processes is well established in drug use and abuse, declarative drug memories have largely been neglected in research. Episodic memories are an important part of the declarative memories. Here a role of episodic drug memories in the establishment of non-addicted drug use and its transition to addiction is suggested. In relation to psychoactive drug consumption, episodic drug memories are formed when a person prepares for consumption, when the drug is consumed and, most important, when acute effects, withdrawal, craving, and relapse are experienced. Episodic drug memories are one-trial memories with emotional components that can be much stronger than “normal” episodic memories. Their establishment coincides with drug-induced neuronal activation and plasticity. These memories may be highly extinction resistant and influence psychoactive drug consumption, in particular during initial establishment and at the transition to “drug instrumentalization.” In that, understanding how addictive drugs interact with episodic memory circuits in the brain may provide crucial information for how drug use and addiction are established. PMID:23734106
Episodic memories and their relevance for psychoactive drug use and addiction.

PubMed

Müller, Christian P

2013-01-01

The majority of adult people in western societies regularly consume psychoactive drugs. While this consumption is integrated in everyday life activities and controlled in most consumers, it may escalate and result in drug addiction. Non-addicted drug use requires the systematic establishment of highly organized behaviors, such as drug-seeking and -taking. While a significant role for classical and instrumental learning processes is well established in drug use and abuse, declarative drug memories have largely been neglected in research. Episodic memories are an important part of the declarative memories. Here a role of episodic drug memories in the establishment of non-addicted drug use and its transition to addiction is suggested. In relation to psychoactive drug consumption, episodic drug memories are formed when a person prepares for consumption, when the drug is consumed and, most important, when acute effects, withdrawal, craving, and relapse are experienced. Episodic drug memories are one-trial memories with emotional components that can be much stronger than "normal" episodic memories. Their establishment coincides with drug-induced neuronal activation and plasticity. These memories may be highly extinction resistant and influence psychoactive drug consumption, in particular during initial establishment and at the transition to "drug instrumentalization." In that, understanding how addictive drugs interact with episodic memory circuits in the brain may provide crucial information for how drug use and addiction are established.
Psychoactive Drugs in Plastic Surgery

PubMed Central

Davison, Steven P.; Hayes, Kylie D.

2017-01-01

Background: Psychoactive drug use is on the rise in the United States, with plastic surgery patients a potentially susceptible group. This study aimed to determine the incidence of cosmetic and reconstructive patients in our practice taking psychoactive drugs and to compare those values with the national average. Furthermore, we discuss the patient safety concerns when patients withhold their medical history information over the course of their treatment. Methods: Urban private plastic practice patients who underwent surgery in a closed practice from 2009 to 2016 were divided into cosmetic and reconstructive cohorts. Review for drug use was medical scripts, history, and Surescripts drug reporting. Extracted information includes age, race, procedure, psychoactive medications, and whether or not they stated a mental health diagnosis on their medical history forms. Only patients with complete records were included. Results: A total of 830 patients were included in statistical analysis. Due to minimal cohort number, 70 men were excluded, as there were no comparative national data. Our analysis found that 33.6% cosmetic patients and 46.3% reconstructive patients used at least one psychoactive drug. Conclusion: There is a statistically significant difference between psychoactive drug use at our practice compared with the general population and a significantly larger percentage of reconstructive patients taking drugs compared with the cosmetic cohort. PMID:28458985
From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

PubMed

Youssef, F F; Irving, A J

2012-06-01

Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the 'holy grail' of endocannabinoid research.
Identification of novel psychoactive drug use in Sweden based on laboratory analysis--initial experiences from the STRIDA project.

PubMed

Helander, Anders; Beck, Olof; Hägerkvist, Robert; Hultén, Peter

2013-08-01

The study aimed to collect information concerning the increasing use of new psychoactive substances, commonly sold through online shops as 'Internet drugs' or 'legal highs', or in terms of masked products such as 'bath salts' and 'plant food'. The Karolinska Institutet and Karolinska University Laboratory and the Swedish Poisons Information Centre have initiated a project called 'STRIDA' aiming to monitor the occurrence and trends of new psychoactive substances in Sweden, and collect information about their clinical symptoms, toxicity and associated health risks. A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-component method has been developed, currently allowing for the determination of > 80 novel psychoactive compounds or metabolites thereof. This study focused mainly on the particular drug substances identified and the population demographics of the initial STRIDA cases. In urine and/or blood samples obtained from 103 consecutive cases of admitted or suspected recreational drug intoxications in mostly young subjects (78% were ≤ 25 years, and 81% were males) presenting at emergency departments all over the country, psychoactive substances were detected in 82%. The substances comprised synthetic cannabinoids ('Spice'; JWH analogues), substituted cathinones ('bath salts'; e.g. butylone, MDPV and methylone) and tryptamines (4-HO-MET), plant-based substances (mitragynine and psilocin), as well as conventional drugs-of-abuse. In 44% of the cases, more than one new psychoactive substance, or a mixture of new and/or conventional drugs were detected. The initial results of the STRIDA project have documented use of a broad variety of new psychoactive substances among mainly young people all over Sweden.
Evaluation of problematic psychoactive substances use in people placed in police custody.

PubMed

Gérardin, Marie; Guigand, Gabriel; Wainstein, Laura; Jolliet, Pascale; Victorri-Vigneau, Caroline; Clément, Renaud

2017-07-01

In France, the law states that any person held in custody could be examined by a doctor. The main objective of the medical examination is to give medical evidence of health compatibility with custody. This review identifies health risks such as addictive behaviour. We wanted to know which psychoactive substances are used in this particular population, and how problematic these uses are. A prospective, monocentric, open-ended study conducted via a structured questionnaire was carried out on detainees who reported having taken drugs or illegal substances. Practitioners investigated desired effects for each substance, and characteristics of use, by means of the dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994). Problematic use was assessed when at least 3 items of the DSM IV were positive. 604 questionnaires were examined. 90.7% of questionnaires reported tobacco use, 76.2% cannabis, 57.3% alcohol, 12.5% psychostimulants, 10.0% opiates and 0.7% benzodiazepines or Z-drugs. The frequency of problematic use was 74.6% for opiates, 44.9% for cocaine and 25.3% for cannabis. Compared to non-problematic users, problematic users were older, more likely to be jobless without financial means, more likely to have a medical history, including a greater likelihood of mental illness, and more chance of undergoing prescribed medical treatment. They included more women and more homeless people. These results show characteristics of psychoactive substance use in a sample of people in custody. Psychoactive substances mentioned by respondents are not different from those observed in the general population, but for certain users, the desired effects are far from the pharmacologically expected ones. For some, taking substances seems to be part of their way of life, for others it is a means to compensate for an underlying feeling of uneasiness. Furthermore, problematic users present severity criteria which seem to be greater than in psychoactive substance users in the general population. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Cannabinoids in health and disease.

PubMed

Kogan, Natalya M; Mechoulam, Raphael

2007-01-01

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.
Cannabinoids in health and disease

PubMed Central

Kogan, Natalya M.; Mechoulam, Raphael

2007-01-01

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable - instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and - in cases where it is impossible to separate the desired clinical action and the psychoactivity - just to monitor these side effects carefully. PMID:18286801
Functional localization in the nucleus rotundus.

DOT National Transportation Integrated Search

1977-10-01

Work has suggested that the effects of psychoactive drugs on visual performance may best be understood, and/or predicted, by studying differential effects of the drugs on functionally differentiated sets of neurones in visual projection systems in th...
[Psychoactive drugs and costs in the Madrid III (Valdemoro) prison].

PubMed

Algora-Donoso, I; Varela-González, O

2008-01-01

Annual pharmaceutical expenditures in prisons increases dramatically and the rising costs of psychoactive drugs have especially contributed to this. These drugs are often prescribed in order to find therapeutic uses in the field of personality disorders, addictions, and dysfunctional behaviours that are not included in the authorized indications (compassionate use). This study has enabled a detailed description of the use of psychoactive drugs at the Madrid III prison, a centre with one of the lowest levels of pharmaceutical expenditure in this autonomous community. During a two-week period, all prescriptions of psychoactive drugs were collected and registered along with data of several possible conditioning factors. 20.5% of the population was receiving some kind of psychoactive drug; 76% of those inmates undergoing treatment were receiving one or two substances; 65% were taking anxiolytics, 38% antidepressants and 27% antipsychotics. The total amount of psychoactive drugs consumed was 9,840 defined daily doses, 46% of which were anxiolytics, 17% antidepressants and 14% antipsychotics. The total cost of the fortnight's treatment was euros 5,379 with a saving of euro 611 due to requesting and selecting offers carried out by the pharmacist. 72% of the costs were spent on anti-psychotics and the newer psychoactive drugs, representing 66% of the prescriptions, accounted for 98% of expenditure. The prescriber was one of the key influential factors over the amount, type and cost of the treatments. There are signs that compassionate use of current antipsychotics and antiepileptics, and newer antidepressants are a main cause of the dramatic increase in the costs, with cost-efficiency not always clearly demonstrated. These results are not an isolated fact restricted only to prisons, as demonstrated by consumption data published by the National Health System in the same year.
Developing Syndromic Surveillance to Monitor and Respond to Adverse Health Events Related to Psychoactive Substance Use: Methods and Applications.

PubMed

Nolan, Michelle L; Kunins, Hillary V; Lall, Ramona; Paone, Denise

Recent increases in drug overdose deaths, both in New York City and nationally, highlight the need for timely data on psychoactive drug-related morbidity. We developed drug syndrome definitions for syndromic surveillance to monitor drug-related emergency department (ED) visits in real time. We used 2012 archived syndromic surveillance data from New York City hospitals to develop definitions for psychoactive drug-related syndromes. The dataset contained ED visit-level information that included patients' chief complaints, dates of visits, ZIP codes of residence, discharge diagnoses, and dispositions. After manually reviewing chief complaints, we developed a classification scheme comprising 3 categories (overdose, drug mention, and drug abuse/misuse), which we used to define 25 psychoactive drug syndromes. From July 2013 through December 2015, the New York City Department of Health and Mental Hygiene performed daily syndromic surveillance of psychoactive drug-related ED visits using the 25 syndrome definitions. Syndromic surveillance triggered 4 public health investigations, supported 8 other public health investigations that had been triggered by other mechanisms, and resulted in the identification of 5 psychoactive drug-related outbreaks. Syndromic surveillance also identified a substantial increase in synthetic cannabinoid-related visits (from an average of 3 per week in January 2014 to >300 per week in July 2015) and an increase in heroin overdose visits (from 80 to 171 in the first 3 quarters of 2012 and 2014, respectively) in a single neighborhood. Syndromic surveillance using these novel definitions enabled monitoring of trends in psychoactive drug-related morbidity, initiation and support of public health investigations, and targeting of interventions. Health departments can refine these definitions for their jurisdictions using the described methods and integrate them into existing syndromic surveillance systems.

Psychoactive substances use experience and addiction or risk of addiction among by Polish adolescents living in rural and urban areas.

PubMed

Pawłowska, Beata; Zygo, Maciej; Potembska, Emilia; Kapka-Skrzypczak, Lucyna; Dreher, Piotr; Kędzierski, Zbigniew

2014-01-01

The objective of the study was to determine the similarities and differences between adolescents with psychoactive substances use experience living in urban and rural areas as regards the intensity of Internet addiction symptoms as well as the evaluation of prevalence of psychoactive substances use among adolescents depending on the place of residence. The examined group consisted of 1 860 people (1 320 girls and 540 boys) their average age being 17 years. In the study the following research methods were used: the Sociodemographic Questionnaire designed by the authors, the Internet Addiction Questionnaire by Potembska, the Internet Addiction test by Young, the Internet Addiction Questionnaire (KBUI) designed by Pawłowska and Potembska. Statistically significant differences were found as regards the prevalence of psychoactive substances use by the adolescents living in urban and rural areas and as regards the intensity of Internet addiction symptoms in adolescents, both from the urban and rural areas, who use and do not use illegal drugs. Significantly more adolescents living in urban areas as compared to their peers living in rural areas use psychoactive substances, mainly marihuana. The adolescents who use psychoactive substances, as compared to the adolescents with no experience using illegal drugs, living both in urban and rural areas significantly more often play online violent games and use web pornography. The adolescents living in rural areas who use psychoactive substances significantly more often as compared to the adolescents who do not use these substances claim that it is only thanks to the interactions established on the Internet that they can get acceptance, understanding and appreciation.
Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State, USA.

PubMed

Subedi, Bikram; Kannan, Kurunthachalam

2015-05-01

The fates of psychoactive pharmaceuticals, including two antischizophrenics, six sedative-hypnotic-anxiolytics, four antidepressants, four antihypertensives, and their select metabolites, were determined in two wastewater treatment plants (WWTPs) in the Albany area of New York. All target psychoactive pharmaceuticals and their metabolites were found at a mean concentration that ranged from 0.98 (quetiapine) to 1220 ng/L (atenolol) in wastewater and from 0.26 (lorazepam) to 1490 ng/g dry weight (sertraline) in sludge. In this study, the fraction of psychoactive pharmaceuticals that was sorbed to suspended particulate matter (SPM) was calculated for the first time. Over 50% of the total mass of aripiprazole, norquetiapine, norsertraline, citalopram, desmethyl citalopram, propranolol, verapamil, and norverapamil was found sorbed to SPM in the influent. The mass loadings, i.e., influx, of target psychoactive pharmaceuticals in WWTPs ranged from 0.91 (diazepam) to 347 mg/d/1000 inhabitants (atenolol), whereas the environmental emissions ranged from 0.01 (dehydro-aripiprazole) to 316 mg/d/1000 inhabitants (atenolol). The highest calculated removal efficiencies were found for antischizophrenics (quetiapine=88%; aripiprazole=71%). However, the removal of some psychoactive pharmaceuticals through adsorption onto sludge was minimal (<1% of the initial mass load), which suggests that bio-degradation and/or chemical-transformation are the dominant mechanisms of removal of these pharmaceuticals in WWTPs. Copyright © 2015 Elsevier B.V. All rights reserved.
[Environmental and genetic factors associated with psychoactive medication use in adult females. A population-based twin study].

PubMed

Rosagro Escámez, Francisco; González-Javier, Francisca; Ordoñana, Juan R

2013-01-01

Our objective is to determine the prevalence and factors associated to psychotropic medication consumption in a sample of adult females. Additionally, this study seeks to analyze the relative contribution of environmental and genetic factors to psychoactive medication use. Sample consists of a population-based cohort comprising 437 pairs of female twins born between 1940 and 1966. Information is collected through individual interviews, and it includes employment status, educational level, partner status, menopause, presence of mental disorders and psychoactive medication use. Logistic regression models are applied. The relative contribution of genetic and environmental factors to interindividual variation is analyzed through the classical twin design. In the past month, 34.0% of the women interviewed had consumed psychoactive medication. Consumption increases with age, in women out of the labor market, menopausal, and reporting a history of mental disorders. When controlling for age, all variables lost significance, except the presence of mental health problems. Heritability estimates for psychoactive medication use was 52%. This estimate is similar (46%) for consumption in the two categories studied. There is a high prevalence of psychoactive medication use in this sample. This consumption is mainly associated with age and presence of mental disorders. About half of the interindividual variation in psychotropic medication use is attributable to genetic factors, while the rest of the variance would be due to environmental factors unique to each individual.
Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

PubMed

Dalterio, S; Steger, R; Mayfield, D; Bartke, A

1984-01-01

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.
The Synthetic Cannabinoids Phenomenon.

PubMed

Karila, Laurent; Benyamina, Amine; Blecha, Lisa; Cottencin, Olivier; Billieux, Joël

2016-01-01

« Spice » is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at this period Health professionals should take into account that limited scientific evidence is available regarding the effect of synthetic cannabinoids use in humans. It thus urges to launch more systematic epidemiological studies, to develop and validate screening procedures, and to investigate the neurobiological and psychological correlates and risk factors associated to synthetic cannabinoids use and misuse. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol.

PubMed

Boggs, Douglas L; Nguyen, Jacques D; Morgenson, Daralyn; Taffe, Michael A; Ranganathan, Mohini

2018-01-01

The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are >550 chemical compounds and >100 phytocannabinoids isolated from cannabis, including Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC-induced anxiety, psychosis, and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from preclinical and human studies, particularly with reference to anxiety and psychosis-like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings, including the individual and interactive effects of CBD and THC.
Forensic electrochemistry: indirect electrochemical sensing of the components of the new psychoactive substance "Synthacaine".

PubMed

Cumba, Loanda R; Kolliopoulos, Athanasios V; Smith, Jamie P; Thompson, Paul D; Evans, Peter R; Sutcliffe, Oliver B; do Carmo, Devaney R; Banks, Craig E

2015-08-21

"Synthacaine" is a New Psychoactive Substance which is, due to its inherent psychoactive properties, reported to imitate the effects of cocaine and is therefore consequently branded as "legal cocaine". The only analytical approach reported to date for the sensing of "Synthacaine" is mass spectrometry. In this paper, we explore and evaluate a range of potential analytical techniques for its quantification and potential use in the field screening "Synthacaine" using Raman spectroscopy, presumptive (colour) testing, High Performance Liquid Chromatography (HPLC) and electrochemistry. HPLC analysis of street samples reveals that "Synthacaine" comprises a mixture of methiopropamine (MPA) and 2-aminoindane (2-AI). Raman spectroscopy and presumptive (colour) tests, the Marquis, Mandelin, Simon's and Robadope test, are evaluated towards a potential in-the-field screening approach but are found to not be able to discriminate between the two when they are both present in the same sample, as is the case in the real street samples. We report for the first time a novel indirect electrochemical protocol for the sensing of MPA and 2-AI which is independently validated in street samples with HPLC. This novel electrochemical approach based upon one-shot disposable cost effective screen-printed graphite macroelectrodes holds potential for in-the-field screening for "Synthacaine".
[Effects of marijuana on cognition: a review form the neurobiological perspective].

PubMed

Torres, Gladys; Fiestas, Fabián

2012-03-01

Marijuana is one of the most commonly used psychoactive substances in society, mainly among youths. Its use has been consistently associated with several health problems, many of which have in common an impairment in the cognitive processes of behavior, including the memory, attention, emotion and decision making. There is evidence suggesting that cannabinoids, marijuana's primary psychoactive substance, have a negative effect in short-term memory, working memory, and decision making. It has also been found that cannabinoids affect attention and the interaction between cognitive events and emotion. This information can be used as an argument of biological plausibility to assess clinical and epidemiological research findings that show that marijuana`s use is associated to problems such as traffic accidents, psychosis, depression and poor academic records, among others.
Alcohol, psychoactive substances and non-fatal road traffic accidents - a case-control study

PubMed Central

2012-01-01

Background The prevalence of alcohol and other psychoactive substances is high in biological specimens from injured drivers, while the prevalence of these psychoactive substances in samples from drivers in normal traffic is low. The aim of this study was to compare the prevalence of alcohol and psychoactive substances in drivers admitted to hospital for treatment of injuries after road traffic accidents with that in drivers in normal traffic, and calculate risk estimates for the substances, and combinations of substances found in both groups. Methods Injured drivers were recruited in the hospital emergency department and drivers in normal conditions were taken from the hospital catchment area in roadside tests of moving traffic. Substances found in blood samples from injured drivers and oral fluid samples from drivers in moving traffic were compared using equivalent cut off concentrations, and risk estimates were calculated using logistic regression analyses. Results In 21.9% of the injured drivers, substances were found: most commonly alcohol (11.5%) and stimulants eg. cocaine or amphetamines (9.4%). This compares to 3.2% of drivers in normal traffic where the most commonly found substances were z-hypnotics (0.9%) and benzodiazepines (0.8%). The greatest increase in risk of being injured was for alcohol combined with any other substance (OR: 231.9, 95% CI: 33.3- 1615.4, p < 0.001), for more than three psychoactive substances (OR: 38.9, 95% CI: 8.2- 185.0, p < 0.001) and for alcohol alone (OR: 36.1, 95% CI: 13.2- 98.6, p < 0.001). Single use of non-alcohol substances was not associated with increased accident risk. Conclusion The prevalence of psychoactive substances was higher among injured drivers than drivers in normal moving traffic. The risk of accident is greatly increased among drivers who tested positive for alcohol, in particular, those who had also ingested one or more psychoactive substances. Various preventive measures should be considered to curb the prevalence of driving under the influence of psychoactive substances as these drivers constitute a significant risk for other road users as well as themselves. PMID:22943663
Generic legislation of new psychoactive drugs.

PubMed

van Amsterdam, Jan; Nutt, David; van den Brink, Wim

2013-03-01

New psychoactive drugs (NPDs, new psychoactive substances) enter the market all the time. However, it takes several months to ban these NPDs and immediate action is generally not possible. Several European countries and drug enforcement officers insist on a faster procedure to ban NPDs. Introduction of generic legislation, in which clusters of psychotropic drugs are banned in advance, has been mentioned as a possible solution. Here we discuss the pros and cons of such an approach. First, generic legislation could unintentionally increase the expenditures of enforcement, black market practices, administrative burden and health risks for users. Second, it may have a negative impact on research and the development of new treatments. Third, due to the complexity of generic legislation, problems in the enforcement are anticipated due to lack of knowledge about the chemical nomenclature. Finally, various legal options are already available to ban the use, sale and trade of NPDs. We therefore conclude that the currently used scientific benefit-risk evaluation should be continued to limit the adverse health effects of NPDs. Only in emergency cases, where fatal incidents (may) occur, should this approach be overruled.
Psychoactive substance use and dependence among Spanish university students: prevalence, correlates, polyconsumption, and comorbidity with depression.

PubMed

Vázquez, Fernando L

2010-02-01

In this study, the prevalence of psychoactive substance use and dependence was estimated among students at a Spanish university, together with associated factors, polyconsumption, and comorbidity with depression, using a 554-member sample stratified by sex, degree year, and discipline. 86.5% had consumed some potentially addictive psychoactive substance in the past month, and 10.5% satisfied DSM-IV criteria for dependence on nicotine, alcohol, caffeine, or cannabis. Polyconsumers (90.4%) consumed an average 3.2 different substances. Current depression implied increased likelihood of having consumed tobacco or psychoactive pharmaceutical drugs in the past month, and DSM-IV symptoms of major depressive episode were shown by 8.6% of 58 substance-dependent participants, 8.7% of 540 past-month legal substance consumers, and 12.1% of 140 past-month illegal substance consumers.
Psychometric properties of the Internalized Stigma of Mental Illness scale adapted for people who use psychoactive substances.

PubMed

Gallo, Verónica Del Valle; Burrone, María Soledad; Fernandez, Alicia Ruth; Boyd, Jennifer E; Abeldaño, Roberto Ariel

2017-01-01

People who consume psychoactive substances may experience situations of social stigma on the part of the society in general, and also situations of internalized-stigma derived from their own consumption of substances. The Internalized Stigma of Mental Illness (ISMI) scale has been shown to be valid and reliable to evaluate the internalized-stigma in people with severe mental disorders, but in Argentina there is no a Spanish version of this scale for use with people who use psychoactive substances. The objective of this work was to evaluate the psychometric properties of the Spanish version of the Internalized Stigma of Mental Illness instrument adapted for people who use psychoactive substances. The work was carried out on a sample of 200 patients older than 18 years under treatment of rehabilitation by consumption of psychoactive substances in a public institution of the city of Córdoba (Argentina) between the years 2014 and 2016. The instrument used was the Internalized Stigma of Mental Illness (ISMI) previously adapted for use in these groups of patients. It was determined the reliability of the scale through Cronbach's coefficients α and factorial structure was analyzed through an exploratory factor analysis. The obtained coefficients showed a high reliability, while in the factorial structure emerged the 4 theoretical dimensions described by Ritsher, namely: social isolation, perceived discrimination, alienation and stereotyping. It is concluded that the scale adapted for people who use psychoactive substances is reliable and with an adequate factorial structure.
The Endocannabinoid System as a Target for Treatment of Breast Cancer

DTIC Science & Technology

2009-08-01

psychoactive constituent of marijuana , as well as other naturally occurring and synthetically derived cannabinoids possess potential therapeutic effects...receptor agonists for therapeutic uses because of their marijuana -like and psychomimetic effects. An alternative promising approach is the indirect
Immunopharmacotherapy: vaccination strategies as a treatment for drug abuse and dependence.

PubMed

Moreno, Amira Y; Janda, Kim D

2009-04-01

Despite intensive efforts for its eradication, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Drug addiction is defined as a disease state in which the body relies on a substance for normal functioning and develops physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state or social life. Psychoactive substances such as cocaine, nicotine, alcohol, and amphetamines are able to cross the blood-brain barrier once ingested and temporarily alter the chemical balance of the brain. Current medications used for the treatment of dependence are typically agonists or antagonists of the drugs of abuse. The complex interrelations of the neuronal circuits have made it difficult to accurately predict the actions of potential agonist/antagonist drugs and have led to undesirable side effects within the central nervous system. Nearly forty years ago, a handful of groups began to explore the possibility of utilizing an individual's own immune machinery to counteract the effects of drug exposure in an approach later termed by our laboratory, immunopharmacotherapy.Immunopharmacotherapy aims to use highly specific antibodies to sequester the drug of interest while the latter is still in the bloodstream. Thus, creation of the antibody-drug complex will blunt crossing of the blood brain barrier (BBB) not only counteracting the reinforcing effects of the drug but also preventing any detrimental side effects on the CNS. In the present mini-review we aim to present a focused summary, including relevant challenges and future directions, of the current state of cocaine and nicotine vaccines as these two programs have been the most successful to date.
Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale.

PubMed

van Schalkwyk, Gerrit I; Wilkinson, Samuel T; Davidson, Larry; Silverman, Wendy K; Sanacora, Gerard

2018-02-01

Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects - in trials, these effects are commonly measured using the Clinician Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine's acute psychoactive effects. Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion. An exploratory factor analysis (EFA) was performed on the CADSS, along with assessment of internal consistency. Qualitative methods were used to conduct in-depth interviews with a subset of these participants to identify key features of the acute ketamine experience, including aspects that may not be captured by the CADSS. The mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal consistency showed a Cronbach's alpha of 0.74. Five CADSS items had low correlations with the total score. EFA lead to a one-factor solution containing 16 items. Five of the six highest loading items involved perceptual disturbances, either of time or sensation. Qualitative analyses of 10 patient narratives revealed two phenomena not captured on the CADSS: disinhibition and a sense of peace. This study was by limited by the absence of other ratings of the participants' experience. Findings suggest that the CADSS partially captures the acute effects of ketamine administration. Further research may seek to validate a revised version of the CADSS that more accurately measures these effects. Copyright © 2017 Elsevier B.V. All rights reserved.
[Current situation on new psychoactive substances abuse among methadone maintenance treatment patients in China].

PubMed

Cheng, Z; Dai, M M; Cao, X B

2018-04-10

Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. However, the features on drug abuse changed in the past decades, and the prevalence of new psychoactive substances abuse potentially somehow offset the achievement of MMT. This paper concised the information on research and surveys of this issue that targeting on the current situation, characteristics, related factors and relevant public health problem on new psychoactive substances abuse, among patients who have been on MMT, in China.
Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats.

PubMed

Parker, Linda A; Mechoulam, Raphael

2003-01-01

Considerable evidence indicates that conditioned gaping in rats reflects nausea in this species that does not vomit. A series of experiments evaluated the potential of psychoactive cannabinoid agonists, delta-9-THC and HU-210, and non-psychoactive cannabinoids, Cannabidiol (CBD) and its dimethylheptyl homolog (CBD-dmh), to interfere with the establishment and the expression of conditioned gaping in rats. All agents attenuated both the establishment and the expression of conditioned gaping. Furthermore, the CB1 antagonist, SR-141716, reversed the suppressive effect of HU-210 on conditioned gaping. Finally, SR-141716 potentiated lithium-induced conditioned gaping, suggesting that the endogenous cannabinoid system plays a role in the control of nausea.
Psychoactive Substance Use and Problematic Internet Use as Predictors of Bullying and Cyberbullying Victimization.

PubMed

Zsila, Ágnes; Orosz, Gábor; Király, Orsolya; Urbán, Róbert; Ujhelyi, Adrienn; Jármi, Éva; Griffiths, Mark D; Elekes, Zsuzsanna; Demetrovics, Zsolt

2018-01-01

Research exploring the relationship between addictions and experiences of bullying suggests that problem behaviors may generally be associated with an increased risk of victimization. The aim of the present study was to examine the role of psychoactive substance use, excessive Internet use, and social support in both traditional offline bullying and online "cyberbullying" victimization in a nationally representative sample of adolescents ( N = 6237; 51% male; M age = 16.62 years, SD = 0.95). Results demonstrated that traditional bullying victimization was associated with cyberbullying victimization. Furthermore, psychoactive substance use and problematic Internet use predicted both traditional bullying and cyberbullying victimization. Finally, perceived social support was found to be an important protective factor against both traditional and cyberbullying victimization. However, psychoactive substance use and problematic Internet use accounted for only a small proportion of variance in victimization.
Nigerian medical students' opinions about individuals who use and abuse psychoactive substances.

PubMed

James, Bawo O; Omoaregba, Joyce O

2013-01-01

Substance use disorders are prevalent in Nigeria. The number of available specialist health providers is inadequate to fill the treatment gap. Interventions can be provided by nonspecialist health providers and have been found to be beneficial. However, attitudes toward substance misuse and misusers can impede the provision of this service. We aimed to determine attitudes of medical trainees toward substance use by utilizing a modified form of the Substance Abuse Attitude Scale (SAAS). Medical students (n = 200) had positive attitudes toward individuals who misuse psychoactive substances. The medial students, however, preferred treatment to be offered by trained specialists and held restrictive views regarding cannabis and alcohol use. More positive attitudes were expressed by participants who were male or had a lifetime history of psychoactive substance use. The role of personal and family-related psychoactive substance use factors are probably associated with attitudinal responses and would require further exploration.
Can Google Searches Predict the Popularity and Harm of Psychoactive Agents?

PubMed

Jankowski, Wojciech; Hoffmann, Marcin

2016-02-25

Predicting the popularity of and harm caused by psychoactive agents is a serious problem that would be difficult to do by a single simple method. However, because of the growing number of drugs it is very important to provide a simple and fast tool for predicting some characteristics of these substances. We were inspired by the Google Flu Trends study on the activity of the influenza virus, which showed that influenza virus activity worldwide can be monitored based on queries entered into the Google search engine. Our aim was to propose a fast method for ranking the most popular and most harmful drugs based on easily available data gathered from the Internet. We used the Google search engine to acquire data for the ranking lists. Subsequently, using the resulting list and the frequency of hits for the respective psychoactive drugs combined with the word "harm" or "harmful", we estimated quickly how much harm is associated with each drug. We ranked the most popular and harmful psychoactive drugs. As we conducted the research over a period of several months, we noted that the relative popularity indexes tended to change depending on when we obtained them. This suggests that the data may be useful in monitoring changes over time in the use of each of these psychoactive agents. Our data correlate well with the results from a multicriteria decision analysis of drug harms in the United Kingdom. We showed that Google search data can be a valuable source of information to assess the popularity of and harm caused by psychoactive agents and may help in monitoring drug use trends.

Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review.

PubMed

Solimini, Renata; Rotolo, Maria C; Pellegrini, Manuela; Minutillo, Adele; Pacifici, Roberta; Busardò, Francesco P; Zaami, Simona

2017-01-01

Powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealer's profits, but also to enhance, to modify or to oppose drug effects. The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse. A literature search up to January 2017 was performed on MEDLINE, Scopus and Web of Science and reports and documents of international agencies or institutions were also searched. Pharmacologically active substances such as: paracetamol, caffeine, dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine, hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine, have been identified over the years. Furthermore, since cocaine and morphine (this latter as a precursor of heroin) are both extracted from natural products, some impurities and minor alkaloids can be present in the final preparation. In this context, it is worth considering that new psychoactive substances are also used as cutting agents. The wide availability of illicit psychotropic drugs is the most serious hazard threatening consumers. Indeed emergency departments are often responsible in evaluating damages caused not only by the base substance, but also by other eventual compounds added to mimic or antagonize drug effects or simply dilute the drug amount, with a possible harmful synergic toxic action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Analysis of psychoactive substances in water by information dependent acquisition on a hybrid quadrupole time-of-flight mass spectrometer.

PubMed

Andrés-Costa, María Jesús; Andreu, Vicente; Picó, Yolanda

2016-08-26

Emerging drugs of abuse, belonging to many different chemical classes, are attracting users with promises of "legal" highs and easy access via internet. Prevalence of their consumption and abuse through wastewater-based epidemiology can only be realized if a suitable analytical screening procedure exists to detect and quantify them in water. Solid-phase extraction and ultra-high performance liquid chromatography quadrupole time-of-flight-mass spectrometry (UHPLC-QqTOF-MS/MS) was applied for rapid suspect screening as well as for the quantitative determination of 42 illicit drugs and metabolites in water. Using this platform, we were able to identify amphetamines, tryptamines, piperazines, pyrrolidinophenones, arylcyclohexylamines, cocainics, opioids and cannabinoids. Additionally, paracetamol, carbamazepine, ibersartan, valsartan, sulfamethoxazole, terbumeton, diuron, etc. (including degradation products as 3-hydroxy carbamazepine or deethylterbuthylazine) were detected. This method encompasses easy sample preparation and rapid identification of psychoactive drugs against a database that cover more than 2000 compounds that ionized in positive mode, and possibility to identify metabolites and degradation products as well as unknown compounds. The method for river water, influent and effluents samples was fully validated for the target psychoactive substances including assessment of matrix effects (-88-67.8%), recovery (42-115%), precision (<19%) and limits of quantification (1-100ngL(-1)). Method efficiency was thoroughly investigated for a wide range of waste and surface waters. Robust and repeatable functioning of this platform in the screening, identification and quantification of traditional and new psychoactive drugs biomarkers and other water contaminants is demonstrated. Copyright © 2016 Elsevier B.V. All rights reserved.
Monitoring the Internet for emerging psychoactive substances available to Australia.

PubMed

Bruno, Raimondo; Poesiat, Rosalie; Matthews, Allison Jane

2013-09-01

Novel psychoactive substances are increasingly available, both in traditional storefronts and via the Internet. While some use of such substances has been captured in Australian consumer surveys and wastewater analyses, there is little information about the products that are available to Australia via the Internet. Systematic monthly Internet monitoring for emerging psychoactive substances was conducted between July 2011 and July 2012. Webstores identified through searches were examined to determine if they sold stimulant or psychedelic emerging psychoactive substances to Australia. Internet search numbers for these products were examined over time using commercial tools. In 12 months, 43 unique webstores were identified selling to Australia, averaging two new webstores per month; however, two-fifths had closed within six months. Over 200 unique chemically unspecified products sold by purported effect (e.g. 'charge') were identified over 12 months, averaging 10 new products per month. Almost half of these products had disappeared from the market within six months. Eighty-six unique chemically specified products (e.g. methylenedioxypyrovalerone) were identified over 12 months, averaging four new novel substances per month. Once released, these products typically remained available, with almost 90% still available for purchase over a 6-month period. Almost 40 000 searches for these products emanated from Australia per month. This market is fast paced as retailers strive to beat both regulatory processes and competitors. Ongoing attention to these markets, incorporating surveillance of both Internet and traditional storefronts, is crucial as several of the substances identified have demonstrated potential for health and neurological harm. © 2013 Australasian Professional Society on Alcohol and other Drugs.
Use of psychoactive substances in persons with spinal cord injury: a literature review.

PubMed

Tétrault, M; Courtois, F

2014-12-01

To undertake a critical review of literature on use of legal and illegal psychoactive substances (PAS) in persons with spinal cord injury (SCI) before and after trauma. Hundred and five articles published between 1980 and 2014 on alcohol and drug use in persons with SCI before and after trauma were retrieved from the PubMed and PsycInfo search engines. Before injury, 25% to 96% of people with SCI reported using alcohol, while 32% to 35% had used illegal drugs. At the time of injury, 31% to 50% of individuals with SCI were intoxicated with alcohol, 16% to 33% with drugs and 26% with a combination of drugs and alcohol. Among those reporting PAS use before injury, up to 50% stated that they had reduced their use during active rehabilitation, during which time only 6% consumed psychoactive substances for the first time. A variety of risk factors are associated with consumption subsequent to spinal cord injury: personality alteration (impulsiveness, aggressiveness), posttraumatic depression, poor coping skills, lack of social support and pain. PAS use can affect the process of rehabilitation, diminish the effectiveness of medication and result in various medical complications. Few studies have explored the use of alcohol, drugs and psychoactive medications before SCI and during active rehabilitation. To our knowledge, no study has analyzed the evolution of PAS use after hospital discharge, even though return home is associated with new stressors that may trigger risky behaviors. It should be a priority, as early as possible during rehabilitation, to detect persons at risk of developing PAS abuse. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Octodrine: New Questions and Challenges in Sport Supplements.

PubMed

Catalani, Valeria; Prilutskaya, Mariya; Al-Imam, Ahmed; Marrinan, Shanna; Elgharably, Yasmine; Zloh, Mire; Martinotti, Giovanni; Chilcott, Robert; Corazza, Ornella

2018-02-20

Background : Octodrine is the trade name for Dimethylhexylamine (DMHA), a central nervous stimulant that increases the uptake of dopamine and noradrenaline. Originally developed as a nasal decongestant in the 1950's, it has recently been re-introduced on the market as a pre-workout and 'fat-burner' product but its use remains unregulated. Our work provides the first observational cross-sectional analytic study on Octodrine as a new drug trend and its associated harms after a gap spanning seven decades. Methods : A comprehensive multilingual assessment of literature, websites, drug fora and other online resources was carried out with no time restriction in English, German, Russian and Arabic. Keywords included Octodrine's synonyms and chemical isomers. Results : Only five relevant publications emerged from the literature search, with most of the available data on body building websites and fora. Since 2015, Octodrine has been advertised online as "the next big thing" and "the god of stimulants," with captivating marketing strategies directed at athletes and a wider cohort of users. Reported side-effects include hypertension, dyspnoea and hyperthermia. Conclusions : The uncontrolled use of Octodrine, its physiological and psychoactive effects raise serious health implications with possible impact on athletes and doping practices. This new phenomenon needs to be thoroughly studied and monitored.
Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives

PubMed Central

Tambaro, Simone; Bortolato, Marco

2013-01-01

Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals. The heterogeneity of cannabis-induced psychological outcomes reflects a complex network of molecular interactions between the key neurobiological substrates of anxiety and fear and the endogenous cannabinoid system, mainly consisting of the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol (2-AG) and two receptors, respectively termed CB1 and CB2. The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself. The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the side effects associated with cannabis consumption. PMID:22280339
Criminal characteristics of a group of primary criminals diagnosed with aspd: approach to criminal recidivis.

PubMed

Larrotta-Castillo, R; Garivia, A M; Mora-Jaimes, C; Gómez-Abril, D A

2017-12-01

Antisocial personality disorder (ASPD) is commonly associated with the risk of criminal recidivism. Knowing more about the factors associated with this pattern of behaviour can help with the design of effective prevention strategies. The purpose of this article is to establish if there are differences in socio-criminogenic variables of a group of criminals sentenced for the first time and with APSD compared to another group of first-time offenders who do not present this disorder. Analytical observation study of 70 men classified into 2 groups according to the presence of ASPD TPA (n=47; age: 29.98±7.8 years) or absence of ASPD (n=23; age: 32.35±8.7 years). The inmates with ASPD showed higher frequencies of current consumption of psychoactive substances (31.9%), criminal associations and simultaneous use of psychoactive substances (70.2%), having committed the crime under the effects of a psychoactive substance (55.3%), not having the possibility of distancing themselves from criminal associations (83%) and a lack of legal resources for proceedings for defence and release (76.6%). This sample contains a group of variables called dynamic that are more commonly present amongst first time offenders with ASPD; said variables have been associated as major predictors of recidivism. Given that they are regarded as dynamic, they may well be modifiable.
New psychoactive substances: Are there any good options for regulating new psychoactive substances?

PubMed

Reuter, Peter; Pardo, Bryce

2017-02-01

Advances in chemistry, technology, and globalization have contributed to the rapid development and diffusion of NPS (new psychoactive substances), creating perhaps the most serious challenge to the century-old international drug control system and to national systems. Very little is known about the effects of these substances which fall outside of national and international controls. The predominant response to the flood of NPS has been the development of more expeditious methods of prohibiting a new chemical entity. This article explores alternative mechanisms that have been considered: foodstuffs, alcohol and tobacco and medicines. None seems promising in terms of avoiding the problems of prohibition without permitting unsafe substances on the market. The article then considers whether there is a bias in the existing system toward excessive prohibition. In public discussion, no attention is given to the pleasures that users obtain from any NPS, to the possibility of substitution for a more dangerous legal or illegal drug or to the consequences of illegal markets for prohibited NPS. On the other hand, it may well be impossible to obtain meaningful assessments on any of these matters at the time when decisions are made. These complexities have led a number of countries, most recently Australia and the UK, to impose total bans, the effects of which are impossible to predict. Copyright © 2016 Elsevier B.V. All rights reserved.
[Use of psychoactive substances and contraceptive methods by the Brazilian urban population, 2005].

PubMed

Bastos, Francisco I; Cunha, Cynthia B; Bertoni, Neilane

2008-06-01

To analyze the relationship between utilization patterns for condoms and other contraceptive methods and the consumption of alcohol and drugs. Exploratory study based on data from a probabilistic sample of 5,040 interviewees aged 16 to 65 years living in large urban regions of Brazil in 2005. The data were collected by means of questionnaires. The chi-square automatic interaction classification tree technique was used to study the use of condoms among interviewees of both sexes and other contraceptive methods among women, at the time of the last vaginal sexual intercourse. Among young and middle-aged adults of both sexes and young men in stable relationships, condom use was less frequent among those who said they used psychoactive substances (alcohol and/or illegal drugs). The possible modulating effect of psychoactive substances on contraceptive practices among mature women seems to be more straightforward, compared to the more subtle effects observed among younger women, for whom the different social classes they belonged to seemed to play a more important role. Despite the limitations resulting from an exploratory study, the fact that this was a representative sample of the urban population of Brazil and not from vulnerable populations, reinforces the need to implement integrated public policies directed towards the general population, with regard to preventing drug consumption, alcohol abuse, sexually transmitted infections, HIV/AIDS and unwanted pregnancy and promoting sexual and reproductive health.
National study of prescription poisoning with psychoactive and nonpsychoactive medications in Medicare/Medicaid dual enrollees age 65 or over.

PubMed

Blackwell, Steven A; Baugh, David K; Ciborowski, Gary M; Montgomery, Melissa A

2011-01-01

The purpose of this study is to assess prescription medication poisoning among psychoactive and nonpsychoactive medications used by elderly (65 years or older) Medicare & Medicaid dual enrollees as well as examine contextual components associated with poisoning. Our primary research goal was to compare medication poisonings among psychoactive medications to nonpsychoactive medications. Our second research goal was to identify components influencing medication poisonings and how they interrelate. The approach used a cross-sectional retrospective review of calendar year 2003 Centers for Medicare & Medicaid Service's Medicaid Pharmacy claims data for elderly dual enrollees. Poisonings were identified based on ICD-9-CM categorizations. Poisonings associated with the psychoactive medications were proportionally over twice as high as compared to nonpsychoactive medications (14.3 per 100,000 enrollees and 6.6 per 100,000 enrollees, respectively). Additionally, the two contextual components of (a) use of many drugs and (b) familiarity with the medication have a direct, but competing impact on poisoning. The reasons behind unintentional poisoning in the elderly have been somewhat a mystery. This study is among the first to attempt to distinguish between poisoning events associated with psychoactive medications versus nonpsychoactive medications as well as assess the impact of differing contextual components on medication poisoning.
The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

PubMed

Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

2011-08-01

Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed.
The Biochemistry of Psychoactive Drugs.

ERIC Educational Resources Information Center

Abood, Leo G.

The effect of psychochemicals on the higher central nervous system, and recent theories regarding drug addiction are discussed. The effect of drugs upon each individual is different. Many drugs have no effect on the brain because of a blood-brain barrier. However, alterations in the rate and character of one's metabolic pattern can lead to…
Maternal hair and neonatal meconium to assess gestational consumption and prenatal exposure to drugs of abuse and psychoactive drugs.

PubMed

Cortes, Laura; Almeida, Laura; Sabra, Sally; Muniesa, Marta; Busardo, Francesco Paolo; Garcia-Algar, Oscar; Gomez-Roig, Maria Dolores

2018-04-05

In the last two decades, the consumption of drugs of abuse among women of childbearing age has experienced a significant increase and results from analyses of surveys concerning maternal intake of psychoactive prescription drugs during pregnancy indicate that the rates of intake are increasing each year. Analyses of biological matrices such as maternal hair and neonatal meconium have recently been used for assessment of gestational consumption and consequent prenatal exposure to drugs of abuse in high-risk groups of women METHODS: Maternal hair and neonatal meconium were analyzed by validated chromatographic mass spectrometric methodologies to disclose gestational use of drugs of abuse and psychoactive prescription drugs and consequent prenatal exposure in a cohort of 513 mother-newborn dyads at the Sant Joan de Déu Barcelona Hospital, Spain, during 2012- 2013. A total of 3.9% the women reported drugs of abuse or prescription psychoactive drug consumption at any time during pregnancy. The prevalence of gestational consumption and consequent prenatal exposure to drugs of abuse (e.g. cannabis, cocaine and MDMA) was 1.2% in maternal hair and 0.4% in meconium; that of psychoactive prescription drugs (e.g. venlafaxine, citalopram, fluoxetine, clomipramine) was 1.7% in maternal hair and 1.2% in meconium. The prevalence of drugs of abuse and prescription psychoactive drug consumption was lower in our specific cohort of Spanish pregnant women than in other cohorts such as those from U.S. or Denmark. Analysis of materno-fetal matrices provides a viable alternative to study prenatal exposure to these substances and develop specific social and health intervention recommendations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Drug effects on responses to emotional facial expressions: recent findings.

PubMed

Miller, Melissa A; Bershad, Anya K; de Wit, Harriet

2015-09-01

Many psychoactive drugs increase social behavior and enhance social interactions, which may, in turn, increase their attractiveness to users. Although the psychological mechanisms by which drugs affect social behavior are not fully understood, there is some evidence that drugs alter the perception of emotions in others. Drugs can affect the ability to detect, attend to, and respond to emotional facial expressions, which in turn may influence their use in social settings. Either increased reactivity to positive expressions or decreased response to negative expressions may facilitate social interaction. This article reviews evidence that psychoactive drugs alter the processing of emotional facial expressions using subjective, behavioral, and physiological measures. The findings lay the groundwork for better understanding how drugs alter social processing and social behavior more generally.
Diversional and physical nonpharmacological interventions for behavioral and psychological symptoms of dementia.

PubMed

Fitzsimmons, Suzanne; Barba, Beth; Stump, Maria

2015-02-01

This article is the last of a four-part series addressing the use of non-pharmacological interventions for older adults with behavioral and psychological symptoms of dementia (BPSD). These types of interventions are used to prevent, lessen, or eliminate BPSD, thereby reducing patient reliance on psychoactive medications. These interventions are easy to use, cost-effective, and simple to implement. The Centers for Medicare & Medicaid Services' psychoactive medication reduction initiative encourages all staff to use nonpharmacological interventions to manage BPSD. As with any attempt to handle BPSD, health care professionals and staff need a tool-box of interventions, as what works one day may not work the next and what works with one older adult may not work with another. This article describes the categories of diversional and physical nonpharmalogical interventions, presents the evidence supporting their use, and provides information on effective implementation. Copyright 2015, SLACK Incorporated.
[Cannabinoid and cathinone designer drugs - the workings and selected methods of analysis].

PubMed

Nędza, Jadwiga; Polaniak, Renata; Bułdak, Rafał J; Majchrzak, Milena; Margasiń-Ska, Joanna; Rojkiewicz, Marcin; Celiński, Rafał; Grochowska-Niedworok, Elżbieta

2016-07-29

Recently, there has been an increase in the consumption of designer drugs, substances aimed at producing psychoactive, energizing, euphoric or anesthetic effects. Designer drugs are substitutes of actual narcotics, whose possession is banned under Polish law according to the Act of 29 July 2005. The latest reports suggest that the number of synthetic psychoactive substances is increasing. In the span of 2012, a total of 28 new synthetic cannabinoids were discovered in member states of the European Union. Synthetic psychoactive substances appear in different forms on the market: tablets (often very colourful and interestingly-shaped), seeds, dried product (sprayed with synthetic substance and redried), crystals or powder. The way of application is greatly diverse, and depends on the form in which a drug is produced and dispensed. The methods of intoxication include smoke inhalation (oftentimes blends are smoked), intranasal or oral application, placing crystals on the eye, or injection. Said methods correspond, with varying degrees, to invoking different psychotic effects, such as agitation, panic attacks, paranoia, hallucinations, overall irritation, and aggression. Various cardiovascular effects, such as tachycardia or increase in blood pressure, may follow as well. However, the primary influence is on the nervous system, inhibiting the reuptake of neurotransmitters such as serotonin, noradrenalin and dopamine, and leading to their increased concentration at the presynaptic cleft, which in turn causes feelings of agitation and pleasure. The knowledge regarding the strength, toxicity, and metabolism of designer drugs is yet sparse. The same pertains to the knowledge regarding the handling of overdose cases. © 2016 MEDPRESS.
Psychoactive plant abuse: the identification of mitragynine in ketum and in ketum preparations.

PubMed

Chan, K B; Pakiam, C; Rahim, Rusyidah A

2005-01-01

Recently, the abuse of ketum, an indigenous psychoactive plant, has received a lot of attention in Malaysia. To help national law enforcement agencies control its abuse, the laboratory of the Forensic Division has developed a procedure for its positive identification. Botanical identification may not be practical or conclusive, owing to the wide range of ketum materials available on the market, including dry macerated leaves, powdered leaves and drinks. In order to confirm that a substance is, in fact, ketum or that a preparation is derived from ketum, gas chromatography-mass spectrometry is used to definitively identify the presence of the psychoactive principle mnitragynine.
In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1.

PubMed

Simmler, Linda D; Buchy, Danièle; Chaboz, Sylvie; Hoener, Marius C; Liechti, Matthias E

2016-04-01

Trace amine-associated receptor 1 (TAAR1) has been implicated in the behavioral effects of amphetamine-type stimulant drugs in rodents. TAAR1 has also been suggested as a target for novel medications to treat psychostimulant addiction. We previously reported that binding affinities at TAAR1 can differ between structural analogs of psychostimulants, and species differences have been observed. In this study, we complement our previous findings with additional substances and the determination of functional activation potencies. In summary, we present here pharmacological in vitro profiles of 101 psychoactive substances at human, rat, and mouse TAAR1. p-Tyramine, β-phenylethylamine, and tryptamine were included as endogenous comparator compounds. Functional cAMP measurements and radioligand displacement assays were conducted with human embryonic kidney 293 cells that expressed human, rat, or mouse TAAR1. Most amphetamines, phenethylamine, and aminoindanes exhibited potentially physiologically relevant rat and mouse TAAR1 activation (EC50 < 5 µM) and showed full or partial (Emax < 80%) agonist properties. Cathinone derivatives, including mephedrone and methylenedioxypyrovalerone, exhibited weak (EC50 = 5-10 µM) to negligible (EC50 > 10 µM) binding properties at TAAR1. Pipradrols, including methylphenidate, exhibited no affinity for TAAR1. We found considerable species differences in activity at TAAR1 among the highly active ligands, with a rank order of rat > mouse > human. This characterization provides information about the pharmacological profile of psychoactive substances. The species differences emphasize the relevance of clinical studies to translationally complement rodent studies on the role of TAAR1 activity for psychoactive substances. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
A multidisciplinary overview of intoxicating snuff rituals in the western hemisphere.

PubMed

de Smet, P A

1985-03-01

Part one of the paper discusses ethnobotanical, chemical and general pharmacological aspects of intoxicating snuff rituals in the western hemisphere. Four categories of ritual snuff ingredients arise from this multidisciplinary approach: It is well established that the plant contains one or more psychoactive principles and the Indian use of the plant as a ritual snuff ingredient is confirmed or quite probable: Anadenanthera, Erythroxylum, Nicotiana, Virola; It is well established that the plant contains one or more psychoactive principles, but the Indian use of the plant as a ritual snuff ingredient is not well recorded or even unlikely: Banisteriopsis, Cannabis, Datura, Ilex guayusa; The Indian use of the plant as a ritual snuff ingredient is confirmed or quite probable, but it is not well established that the plant contains one or more psychoactive principles: Justicia pectoralis, Pagamea macrophylla, Tanaecium nocturnum; The Indian use of the plant as a ritual snuff ingredient is not well recorded, and it is not well established that the plant contains one or more psychoactive principles: Acorus calamus, Capsicum, Macquira sclerophylla, Piper interitum. Part two of the paper discusses the nasal pharmacokinetics and efficacy of possible ritual snuff constituents. The literature yields convincing clinical evidence that atropine, cocaine, nicotine and scopolamine are effective following nasal application, but experimental confirmation of the efficacy of nasal tryptamine alkaloids is still awaited. In self-experiments, 6.4 mg/kg of caffeine produced substantial plasma levels via the nasal route, but 0.5 mg/kg of harmine did not produce measurable plasma levels, when taken as a nasal powder. Without additional experiments, it is difficult to give a definite explanation for this negative result.
[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

Psycho-Active Pharmaceuticals and Military Performance in an Ethical Perspective

DTIC Science & Technology

2009-10-01

the world wide operating mass media , more conscientiousness is needed in operating these manned weapon systems. Psycho-active pharmaceuticals are...moral responsibility in the military. American Journal of Bioethics , vol 8, no.2, pp.28-38. 6.0 Netherlands Department of Defense Disclaimer The
Audit of Psychoactive Drug Prescriptions in Group Homes.

ERIC Educational Resources Information Center

Gowdey, Charles W.; And Others

1987-01-01

The survey found that of the 1,389 mentally retarded persons living in community supervised residential settings in Southwestern Ontario, 49 percent received some type of psychoactive drug. Specifically, 23 percent received anticonvulsants; 14 percent, neuroleptics; 5 percent, sedative/hypnotics; 3 percent, antidepressants; 3 percent,…
[Non-drug psycho-active substance use and pregnancy].

PubMed

El Ammouri, A; Sabir, M; Ahid, S; Toufiq, J; El Omari, F

2015-09-01

The consumption of psycho-active substances (PAS) by pregnant women is in a growing increase around the world. It is a major problem of public health in some countries due to serious and negative consequences for children and society as well as for pregnant women. This problem has also increased among women in Morocco. However, it is still neglected and underrated in the absence of any official statistical data. This is the first study leading to a better profiling of pregnant women who may consume psycho-active substances during their pregnancy; it would permit better medical and psychosocial care of both women and children. To determine the prevalence and the factors associated with the psycho-active substances used by pregnant women and describe their socio-demographic characteristics. A trans-sectional study was carried out from September to October 2010, including pregnant women consulting at the obstetrical service of the provincial hospital Moulay Abdellah in the city of Salé. The study included women who were pregnant or had recently given birth, and not having any serious mental disorders that could have upset their cognitive abilities. The data was collected through a straight questionnaire of 25 items specifying the socio-demographic characteristics, data about pregnancy and habits of using psycho-active substances. One hundred and fifty pregnant women were included in the study. The majority of them (83.2%) were aged 20 to 40 years old, 94.6% were married, 96% were unemployed and depended on their spouses for their financial resources and 80% had normal domestic relationships (from average to good quality). Among the women, 31.3% of them reported traumatic events in the past. The prevalence of psycho-active substance consumption by the pregnant women of our sample was 11.3%. The used substances were tobacco (9.3%) and cannabis (4%). These women were more likely to have a low level of education (47.1 vs 16.5). They were victims of abuse or neglect in their past (82.3 vs 24.9), and their relationships with their spouses were bad (70.6 vs 13.5) with a lack of desired pregnancy (47.1 vs 27.8) and poor follow-up (47.1 vs 3.8). The results show statistically significant differences. Not only should decision-makers draw attention to the seriousness of the problem because of the relatively high rate of psycho-active substance consumption, but also they should increase obstetric team's awareness to look systematically for psycho-active substance use. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.
Importance of Toxicokinetics to Assess the Utility of Zebrafish Larvae as Model for Psychoactive Drug Screening Using Meta-Chlorophenylpiperazine (mCPP) as Example

PubMed Central

Kirla, Krishna Tulasi; Groh, Ksenia J.; Poetzsch, Michael; Banote, Rakesh Kumar; Stadnicka-Michalak, Julita; Eggen, Rik I. L.; Schirmer, Kristin; Kraemer, Thomas

2018-01-01

The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the ever-increasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish (Danio rerio) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete. We here explore the toxicokinetics and behavioral effects of an NPS, meta-chlorophenylpiperazine (mCPP), in zebrafish larvae. Uptake kinetics of mCPP, supported by toxicokinetic modeling, strongly suggested the existence of active transport processes. Internal distribution showed a dominant accumulation in the eye, implying that in zebrafish, like in mammals, melanin could serve as a binding site for basic drugs. We confirmed this by demonstrating significantly lower drug accumulation in two types of hypo-pigmented fish. Comparison of the elimination kinetics between mCPP and previously characterized cocaine demonstrated that drug affinities to melanin in zebrafish vary depending on the structure of the test compound. As expected from mCPP-elicited responses in rodents and humans, zebrafish larvae displayed hypoactive behavior. However, significant differences were seen between zebrafish and rodents with regard to the concentration-dependency of the behavioral response and the comparability of tissue levels, corroborating the need to consider the organism-internal distribution of the chemical to allow appropriate dose modeling while evaluating effects and concordance between zebrafish and mammals. Our results highlight commonalities and differences of mammalian versus the fish model in need of further exploration. PMID:29755353
Importance of Toxicokinetics to Assess the Utility of Zebrafish Larvae as Model for Psychoactive Drug Screening Using Meta-Chlorophenylpiperazine (mCPP) as Example.

PubMed

Kirla, Krishna Tulasi; Groh, Ksenia J; Poetzsch, Michael; Banote, Rakesh Kumar; Stadnicka-Michalak, Julita; Eggen, Rik I L; Schirmer, Kristin; Kraemer, Thomas

2018-01-01

The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the ever-increasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish ( Danio rerio ) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete. We here explore the toxicokinetics and behavioral effects of an NPS, meta-chlorophenylpiperazine (mCPP), in zebrafish larvae. Uptake kinetics of mCPP, supported by toxicokinetic modeling, strongly suggested the existence of active transport processes. Internal distribution showed a dominant accumulation in the eye, implying that in zebrafish, like in mammals, melanin could serve as a binding site for basic drugs. We confirmed this by demonstrating significantly lower drug accumulation in two types of hypo-pigmented fish. Comparison of the elimination kinetics between mCPP and previously characterized cocaine demonstrated that drug affinities to melanin in zebrafish vary depending on the structure of the test compound. As expected from mCPP-elicited responses in rodents and humans, zebrafish larvae displayed hypoactive behavior. However, significant differences were seen between zebrafish and rodents with regard to the concentration-dependency of the behavioral response and the comparability of tissue levels, corroborating the need to consider the organism-internal distribution of the chemical to allow appropriate dose modeling while evaluating effects and concordance between zebrafish and mammals. Our results highlight commonalities and differences of mammalian versus the fish model in need of further exploration.
Cannabinoids as Anticancer Drugs.

PubMed

Ramer, Robert; Hinz, Burkhard

2017-01-01

The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics' effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression. © 2017 Elsevier Inc. All rights reserved.
Psychoactive Substance Use and School Performance among Adolescents in Public Secondary Schools in Uganda

ERIC Educational Resources Information Center

Rukundo, Aloysius; Kibanja, Grace; Steffens, Karl

2014-01-01

Introduction: Psychoactive substance use among adolescents influences behavioral and cognitive processes and is associated with adolescents' performance in school. We therefore sought to investigate association of PASU with adolescents' school performance. Methods: We employed quantitative methods of data collection and analysis. To test the…
Drug effects on responses to emotional facial expressions: recent findings

PubMed Central

Miller, Melissa A.; Bershad, Anya K.; de Wit, Harriet

2016-01-01

Many psychoactive drugs increase social behavior and enhance social interactions, which may, in turn, increase their attractiveness to users. Although the psychological mechanisms by which drugs affect social behavior are not fully understood, there is some evidence that drugs alter the perception of emotions in others. Drugs can affect the ability to detect, attend to, and respond to emotional facial expressions, which in turn may influence their use in social settings. Either increased reactivity to positive expressions or decreased response to negative expressions may facilitate social interaction. This article reviews evidence that psychoactive drugs alter the processing of emotional facial expressions using subjective, behavioral, and physiological measures. The findings lay the groundwork for better understanding how drugs alter social processing and social behavior more generally. PMID:26226144
Plasticity and Functions of the Orbital Frontal Cortex

ERIC Educational Resources Information Center

Kolb, Bryan; Pellis, Sergio; Robinson, Terry E.

2004-01-01

We compare the effects of psychoactive drugs such as morphine and amphetamine on the synaptic organization of neurons in the orbital frontal (OFC) and medial frontal (mPFC) regions in the rat. Both regions are altered chronically by exposure to intermittent doses of either drug but the effects are area-dependent. For example, whereas morphine…
42 CFR 2a.1 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... research on mental health, including research on the use and effect of alcohol and other psychoactive drugs... engaged in research on mental health including research on the use and effect of alcohol and other... 42 Public Health 1 2011-10-01 2011-10-01 false Applicability. 2a.1 Section 2a.1 Public Health...
42 CFR 2a.1 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... research on mental health, including research on the use and effect of alcohol and other psychoactive drugs... engaged in research on mental health including research on the use and effect of alcohol and other... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 2a.1 Section 2a.1 Public Health...
"Legal Highs"--An Emerging Epidemic of Novel Psychoactive Substances.

PubMed

Zawilska, Jolanta B

2015-01-01

During the last decade, there has been an increase in the availability and use of novel psychoactive substances (NPS), also known as "legal highs," across the world. They include a wide range of products, from natural plant-originated substances to synthetic compounds, that can be purchased both online and from high street retailers. "Legal highs" mimic psychoactive effects of illicit drugs of abuse. However, they are claimed to consist of compounds that are legal to sell, possess, and use, often labeled as "not for human consumption" to circumvent drug abuse legislation. Based on the spectrum of their actions on cognitive processes, mood, and behavior, "legal highs" can be classified into four basis categories: amphetamine- and ecstasy-like stimulants, synthetic cannabinoids (SCs), hallucinogenic/dissociative, and opioid-like compounds. NPS may, however, exhibit a combination of these actions due to their designed chemical structure. Although the prevalence and pattern of NPS use differ between various countries, the most popular groups are SCs and psychostimulants, described in this chapter. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these substances. However, the number of intoxicated people presenting with emergencies is constantly increasing, providing evidence that negative health and social consequences may indeed seriously affect recreational and chronic users. © 2015 Elsevier Inc. All rights reserved.
Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter-observational study.

PubMed

Acciavatti, Tiziano; Lupi, Matteo; Santacroce, Rita; Aguglia, Andrea; Attademo, Luigi; Bandini, Laura; Ciambrone, Paola; Lisi, Giulia; Migliarese, Giovanni; Pinna, Federica; Quattrone, Diego; Ribolsi, Michele; Signorelli, Maria Salvina; Calò, Salvatore; Schifano, Fabrizio; di Giannantonio, Massimo; Martinotti, Giovanni

2017-05-01

Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample. Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age 22.24; SD 2.87). About 8.2% of the sample declared to have used NPS at least once, and 2.2% had consumed NPS in the previous 3 months. The three psychiatric diagnoses most frequently associated with NPS use were bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%). In univariate regression analysis, bipolar disorder was positively associated with NPS consumption, an association that did not reach statistical significance in the multivariate analysis. The use of NPS in a young psychiatric population appears to be frequent, and probably still underestimated. Bipolar disorder shows an association with NPS use. Careful and constant monitoring and an accurate evaluation of possible clinical effects related to NPS use are necessary. Copyright © 2017 John Wiley & Sons, Ltd.
Parental Guidance about Drinking: Relationship with Teenage Psychoactive Substance Use

ERIC Educational Resources Information Center

Miller, Patrick; Plant, Martin

2010-01-01

Parental guidance concerning alcohol was explored using data from a 2007 survey of 2179 UK school students aged 15 and 16 years. Cluster analysis based on questions about parental advice was used to establish seven student groups. Associations between groups, other family background and psychoactive substance use variables were explored. Substance…
The Ability of Individuals with Psychoactive Substance Use Disorders to Escape Detection by the Personality Assessment Inventory.

ERIC Educational Resources Information Center

Fals-Stewart, William

1996-01-01

The ability of individuals with psychoactive substance use disorders to dissimulate successfully on the Personality Assessment Inventory (PAI) was evaluated with 236 adults from treatment, nonclinical, control, and forensically referred groups. Findings indicate that the PAI scales measuring drug and alcohol problems are susceptible to…
Longitudinal Prescribing Patterns for Psychoactive Medications in Community-Based Individuals with Developmental Disabilities: Utilization of Pharmacy Records

ERIC Educational Resources Information Center

Lott, I. T.; McGregor, M.; Engelman, L.; Touchette, P.; Tournay, A.; Sandman, C.; Fernandez, G.; Plon, L.; Walsh, D.

2004-01-01

Little is known about longitudinal prescribing practices for psychoactive medications for individuals with intellectual disabilities and developmental disabilities (IDDD) who are living in community settings. Computerized pharmacy records were accessed for 2344 community-based individuals with IDDD for whom a total of 3421 prescriptions were…
Delirium and exposure to psychoactive medications in critically ill adults: A multi-centre observational study.

PubMed

Burry, Lisa D; Williamson, David R; Mehta, Sangeeta; Perreault, Marc M; Mantas, Ioanna; Mallick, Ranjeeta; Fergusson, Dean A; Smith, Orla; Fan, Eddy; Dupuis, Sebastien; Herridge, Margaret; Rose, Louise

2017-12-01

Investigate the relationship between psychoactive drugs and delirium. Prospective observational study of 520 critically ill adult patients admitted ≥24h to 6 intensive care units (ICUs). Data were collected on psychoactive drug exposure, use of sedation administration strategies, and incident delirium (Intensive Care Delirium Screening Checklist score≥4). Delirium was detected in 260 (50%) patients, median (IQR) duration 2 (1-5) days, and time to onset 3 (2-5) days. Delirious patients received more low-potency anticholinergic (P<0.0001), antipsychotic (P<0.0001), benzodiazepine (P<0.0001) and non-benzodiazepine sedative (P<0.0001), and opioid (P=0.0008) drugs. Primary regression (24-hours preceding drug exposure) revealed no association between any psychoactive drug and delirium. Post-hoc analysis (extended 48-hour exposure) revealed an association between delirium and high-potency anticholinergic (HR 2.45, 95% CI 1.08-5.54) and benzodiazepine (HR 1.08 per 5mg midazolam-equivalent increment, 95% CI 1.04-1.12) drugs. Delirious patients had longer ICU (P<0.0001) and hospital (P<0.0001) length of stay, and higher ICU and hospital mortality (P=0.003 and P=0.007, respectively). The identification of psychoactive drugs as modifiable delirium risk factors plays an important role in the management of critically ill patients. This is particularly important given the burden of exposure and combinations of drugs used in this vulnerable patient population. Copyright © 2017 Elsevier Inc. All rights reserved.
Positive Health: Designs for Action.

ERIC Educational Resources Information Center

Beyrer, Mary K.; And Others

This book is designed to assist young adults in making decisions regarding personal health and health behavior. Personal effectiveness, sexuality, psychoactive drugs, nutrition, disease, injury, community and environmental health, and the problems of pollution are discussed in terms of principles, choices, and risk-reduction. Discussion problems…
Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid

PubMed Central

Merrick, John; Lane, Brian; Sebree, Terri; Yaksh, Tony; O'Neill, Carol; Banks, Stan L.

2016-01-01

Abstract Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ9-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Methods: Materials included synthetic CBD, Δ8-THC, and Δ9-THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium dodecyl sulfate (SDS). Samples were analyzed using chromatography with UV and mass spectrometry detection. An assessment time of 3 h was chosen as representative of the maximal duration of exposure to gastric fluid. Results: CBD in SGF with 1% SDS was degraded about 85% after 60 min and more than 98% at 120 min. The degradation followed first-order kinetics at a rate constant of −0.031 min−1 (R2=0.9933). The major products formed were Δ9-THC and Δ8-THC with less significant levels of other related cannabinoids. CBD in physiological buffer performed as a control did not convert to THC. Confirmation of THC formation was demonstrated by comparison of mass spectral analysis, mass identification, and retention time of Δ9-THC and Δ8-THC in the SGF samples against authentic reference standards. Conclusions: SGF converts CBD into the psychoactive components Δ9-THC and Δ8-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored. PMID:28861485
[Ethanol and other psychoactive substances in fatal road traffic accidents in the Czech Republic in 2008].

PubMed

Mravcík, Viktor; Zábranský, Tomás; Vorel, Frantisek

2010-01-01

To map the recent prevalence of alcohol and other psychoactive substances in deceased victims of traffic accidents in the Czech Republic. The studied sample consisted of individuals autopsied in the departments of forensic medicine who died during traffic accidents in 2008 and were toxicologically tested for one or more of the following substances: ethanol, volatile substances, cannabis, opiates, stimulants, cocaine, benzodiazepines, and barbiturates. Case definition involved alcohol cases with blood alcohol concentration (BAC) 0.2 g/kg and higher; with cannabis, detections of active THC metabolites only were taken into account; from cases where volatile substances (solvents) were detected we included into the positive cases only those where substances were not produced post mortem or in some physiological or pathological statuses. The sample consisted of 1,040 persons deceased in traffic accidents, of whom 582 (56.0%) were toxicologically tested for one or more of the substances listed above. The sample has been divided into two subsamples--one of 778 (74.8%) active participants of road traffic accidents (pedestrians, bicyclists, and drivers) and other subsample consisting of 262 (25.4%) non-active participants. Ethanol was found in 38.3% of 381 tested and at least one of other psychoactive substances was found in 11.7% of 384 tested active participants--of those, stimulants (mostly methamphetamine) were found most frequently (6.5% of 337 tested), cannabis (5.9% of 203 tested) and benzodiazepines (3.9% of 363 tested active participants). Drivers were positive for ethanol in 29.2% cases, for one or more of other psychoactive substances except ethanol in 12.7% cases, most frequently for stimulants (9.2%) and cannabis (6.2%). Professional drivers were found negative for ethanol and other psychoactive substance except of one case of methamphetamine (6.7%). The study confirms high prevalence of alcohol and other psychoactive substances, especially stimulants (methamphetamine), cannabis and benzodiazepines, among deceased participants of road traffic accidents including drivers in the Czech Republic.

Multiple Factors in the Long-Term Effectiveness of Contingent Electric Shock Treatment for Self-Injurious Behavior: A Case Example.

ERIC Educational Resources Information Center

Linscheid, Thomas R.; Reichenbach, Heidi

2002-01-01

Data are presented to document the initial dramatic reduction in self-injurious behavior and the ongoing effectiveness of contingent electric shock treatment of an adolescent. Positive effects of the intervention are documented, as is information on the interaction of a medical condition, psychoactive mediation status, and staff changes. (Contains…
Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products.

PubMed

Baumann, Michael H; Partilla, John S; Lehner, Kurt R; Thorndike, Eric B; Hoffman, Alexander F; Holy, Marion; Rothman, Richard B; Goldberg, Steven R; Lupica, Carl R; Sitte, Harald H; Brandt, Simon D; Tella, Srihari R; Cozzi, Nicholas V; Schindler, Charles W

2013-03-01

The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [(3)H]dopamine (IC(50)=4.1 nM) and [(3)H]norepinephrine (IC(50)=26 nM) with high potency but has weak effects on uptake of [(3)H]serotonin (IC(50)=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.
Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts' Products

PubMed Central

Baumann, Michael H; Partilla, John S; Lehner, Kurt R; Thorndike, Eric B; Hoffman, Alexander F; Holy, Marion; Rothman, Richard B; Goldberg, Steven R; Lupica, Carl R; Sitte, Harald H; Brandt, Simon D; Tella, Srihari R; Cozzi, Nicholas V; Schindler, Charles W

2013-01-01

The abuse of psychoactive ‘bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [3H]dopamine (IC50=4.1 nℳ) and [3H]norepinephrine (IC50=26 nℳ) with high potency but has weak effects on uptake of [3H]serotonin (IC50=3349 nℳ). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1–0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1–3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of ‘bath salts' preparations. PMID:23072836
Candyflipping and Other Combinations: Identifying Drug–Drug Combinations from an Online Forum

PubMed Central

Chary, Michael; Yi, David; Manini, Alex F.

2018-01-01

Novel psychoactive substances (NPS) refer to synthetic compounds or derivatives of more widely known substances of abuse that have emerged over the last two decades. Case reports suggest that users combine substances to achieve desired psychotropic experiences while reducing dysphoria and unpleasant somatic effects. However, the pattern of combining NPS has not been studied on a large scale. Here, we show that posts discussing NPS describe combining nootropics with sedative-hypnotics and stimulants with plant hallucinogens or psychiatric medications. Discussions that mention sedative-hypnotics most commonly also mention hallucinogens and stimulants. We analyzed 20 years of publicly available posts from Lycaeum, an Internet forum dedicated to sharing information about psychoactive substance use. We used techniques from natural language processing and machine learning to identify NPS and correlate patterns of co-mentions of substances across posts. We found that conversations mentioning synthetic hallucinogens tended to divide into those mentioning hallucinogens derived from amphetamine and those derived from ergot. Conversations that mentioned synthetic hallucinogens tended not to mention plant hallucinogens. Conversations that mention bath salts commonly mention sedative-hypnotics or nootropics while more canonical stimulants are discussed with plant hallucinogens and psychiatric medications. All types of substances are frequently compared to MDMA, DMT, cocaine, or atropine when trying to describe their effects. Our results provide the largest analysis to date of online descriptions of patterns of polysubstance use and further demonstrate the utility of social media in learning about trends in substance use. We anticipate this work to lead to a more detailed analysis of the knowledge contained online about the patterns of usage and effects of novel psychoactive substances. PMID:29760666
Effects of the new psychoactive substances diclofensine, diphenidine, and methoxphenidine on monoaminergic systems.

PubMed

Luethi, Dino; Hoener, Marius C; Liechti, Matthias E

2018-01-15

Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances (NPSs) that recently appeared on the illicit drug market. Pharmacological profiling of such newly emerged drugs is crucial for a better understanding of their psychotropic effects and toxicity. We therefore investigated the potential of these NPSs to inhibit the norepinephrine, dopamine, and serotonin transporters in human embryonic kidney cells stably transfected with the respective transporters. In addition, we determined monoamine transporter and receptor affinities for the substances. Diclofensine potently bound to the monoamine transporters in the submicromolar range and had similar inhibition potential for all three transporters in the range of 2.5-4.8μM. Moreover, diclofensine bound to adrenergic, dopamine, serotonin, and trace amine-associated receptors. Diphenidine was an equipotent inhibitor of the norepinephrine and dopamine transporters in the low micromolar range and a very weak inhibitor of the serotonin transporter. Besides binding to transporters, diphenidine bound to adrenergic α 1A and α 2A receptors and serotonin 5-hydroxytryptamine 1A (5-HT 1A ) and 5-HT 2A receptors in the range of 4-11μM. Methoxphenidine bound to all transporters, but considerable inhibition (IC 50 < 10μM) was observed only for the norepinephrine transporter. Moreover, methoxphenidine bound to adrenergic α 2A and serotonin 5-HT 2A and 5-HT 2C receptors in the range of 2.5-8.2μM. None of the test drugs mediated substrate-type efflux of monoamines. These data demonstrate that the monoamine transporter inhibition and receptor interactions most likely mediate the psychoactive effects of diclofensine and possibly play a contributory role for diphenidine and methoxphenidine. Copyright © 2017 Elsevier B.V. All rights reserved.
Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine.

PubMed

Thurner, Patrick; Stary-Weinzinger, Anna; Gafar, Hend; Gawali, Vaibhavkumar S; Kudlacek, Oliver; Zezula, Juergen; Hilber, Karlheinz; Boehm, Stefan; Sandtner, Walter; Koenig, Xaver

2014-02-01

Ibogaine is a psychoactive indole alkaloid. Its use as an antiaddictive agent has been accompanied by QT prolongation and cardiac arrhythmias, which are most likely caused by human ether a go-go-related gene (hERG) potassium channel inhibition. Therefore, we studied in detail the interaction of ibogaine with hERG channels heterologously expressed in mammalian kidney tsA-201 cells. Currents through hERG channels were blocked regardless of whether ibogaine was applied via the extracellular or intracellular solution. The extent of inhibition was determined by the relative pH values. Block occurred during activation of the channels and was not observed for resting channels. With increasing depolarizations, ibogaine block grew and developed faster. Steady-state activation and inactivation of the channel were shifted to more negative potentials. Deactivation was slowed, whereas inactivation was accelerated. Mutations in the binding site reported for other hERG channel blockers (Y652A and F656A) reduced the potency of ibogaine, whereas an inactivation-deficient double mutant (G628C/S631C) was as sensitive as wild-type channels. Molecular drug docking indicated binding within the inner cavity of the channel independently of the protonation of ibogaine. Experimental current traces were fit to a kinetic model of hERG channel gating, revealing preferential binding of ibogaine to the open and inactivated state. Taken together, these findings show that ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time.
The Aging Process and Psychoactive Drug Use. Services Research Monograph Series.

ERIC Educational Resources Information Center

Stanford Research Inst., Menlo Park, CA.

This three-phase literature review focusses on the dangers of drug misuse or abuse by the elderly, and seeks to assist in the development of prevention and treatment strategies. The first phase focusses on the aging process and psychoactive drug use in clinical treatment. The second phase identifies and synthesizes information on the patterns of…
Perspectives on the History of Psychoactive Substance Use; Research Issues 24.

ERIC Educational Resources Information Center

Austin, Gregory A.

This collection of resources contains 34 studies which summarize significant developments within the history of psychoactive substance use in developed countries since the sixteenth century. The primary intent of this volume is to provide a greater awareness of the ubiquity of drug use in the past and of the complex and varied factors which have…
Using Internet Snapshot Surveys to Enhance Our Understanding of the Availability of the Novel Psychoactive Substance Alpha-methyltryptamine (AMT).

PubMed

Wood, David Michael; Dargan, Paul Ivor

2013-07-02

Alpha-methyltryptamine (AMT) is a novel psychoactive substance available over the Internet. This study used European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Internet snapshot methodology to investigate the availability and cost of AMT in March/October 2012. From March to October 2012, there was a decrease in the number of Internet sites selling AMT (44 to 31). AMT powder was cheaper in "bulk" (100 g) than in "recreational-user" (100 mg) quantities, and there was a decrease in price. Data from Internet snapshot surveys complement and allow triangulation of data from other sources to build a more detailed picture on availability and use of novel psychoactive substances.
Octodrine: New Questions and Challenges in Sport Supplements

PubMed Central

Catalani, Valeria; Marrinan, Shanna; Elgharably, Yasmine; Chilcott, Robert

2018-01-01

Background: Octodrine is the trade name for Dimethylhexylamine (DMHA), a central nervous stimulant that increases the uptake of dopamine and noradrenaline. Originally developed as a nasal decongestant in the 1950’s, it has recently been re-introduced on the market as a pre-workout and ‘fat-burner’ product but its use remains unregulated. Our work provides the first observational cross-sectional analytic study on Octodrine as a new drug trend and its associated harms after a gap spanning seven decades. Methods: A comprehensive multilingual assessment of literature, websites, drug fora and other online resources was carried out with no time restriction in English, German, Russian and Arabic. Keywords included Octodrine’s synonyms and chemical isomers. Results: Only five relevant publications emerged from the literature search, with most of the available data on body building websites and fora. Since 2015, Octodrine has been advertised online as “the next big thing” and “the god of stimulants,” with captivating marketing strategies directed at athletes and a wider cohort of users. Reported side-effects include hypertension, dyspnoea and hyperthermia. Conclusions: The uncontrolled use of Octodrine, its physiological and psychoactive effects raise serious health implications with possible impact on athletes and doping practices. This new phenomenon needs to be thoroughly studied and monitored. PMID:29461475
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors

PubMed Central

Xiong, Wei; Cui, Tanxing; Cheng, Kejun; Yang, Fei; Chen, Shao-Rui; Willenbring, Dan; Guan, Yun; Pan, Hui-Lin; Ren, Ke; Xu, Yan

2012-01-01

Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction. PMID:22585736
Controlling new drugs under marketing regulations.

PubMed

Hughes, Brendan; Winstock, Adam R

2012-11-01

The rapid emergence of myriad substances openly marketed as 'legal highs' is straining traditional drug control systems which require time and basic scientific data on harms to react, presenting governments with the dilemma of no response or a disproportionate response. Some countries have side-stepped this using novel policy and legislative approaches. Should other countries consider them? We review the different laws invoked to stop the open sale of new psychoactive substances, focusing on the European Union (EU). Some countries have designed new catch-all control systems, or faster systems to classify substances as drugs. Others have enforced consumer safety or medicines legislation to stop the open sale of these products. The latter originate from harmonization of the internal market of the EU. Rigorous, objective evaluation is required, but first results suggest that these have been effective, while avoiding criminalization of users. Every EU country should have existing laws for protecting public health that can be applied swiftly yet proportionately to new drugs appearing on the open market with minimum political involvement. It seems the key is the speed, not the weight, of response. Given support for their enforcement mechanisms, these systems might be as effective and more efficient than the old ones. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.
Cannabis, cannabinoids, and health.

PubMed

Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-09-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (toward a higher proportion of Δ 9 -THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.
Substance abuse and developments in harm reduction.

PubMed

Cheung, Y W

2000-06-13

A drug is a substance that produces a psychoactive, chemical or medicinal effect on the user. The psychoactive effect of mood-altering drugs is modulated by the user's perception of the risks of drug use, his or her ability to control drug use and the demographic, socioeconomic and cultural context. The ability to control drug use may vary along a continuum from compulsive use at one end to controlled use at the other. The "drug problem" has been socially constructed, and the presence of a moral panic has led to public support for the prohibitionist approach. The legalization approach has severely attacked the dominant prohibitionist approach but has failed to gain much support in society because of its extreme libertarian views. The harm reduction approach, which is based on public health principles, avoids the extremes of value-loaded judgements on drug use and focuses on the reduction of drug-related harm through pragmatic and low-threshold programs. This approach is likely to be important in tackling the drug problem in the 21st century.
Substance abuse and developments in harm reduction

PubMed Central

Cheung, Y W

2000-01-01

A drug is a substance that produces a psychoactive, chemical or medicinal effect on the user. The psychoactive effect of mood-altering drugs is modulated by the user's perception of the risks of drug use, his or her ability to control drug use and the demographic, socioeconomic and cultural context. The ability to control drug use may vary along a continuum from compulsive use at one end to controlled use at the other. The "drug problem" has been socially constructed, and the presence of a moral panic has led to public support for the prohibitionist approach. The legalization approach has severely attacked the dominant prohibitionist approach but has failed to gain much support in society because of its extreme libertarian views. The harm reduction approach, which is based on public health principles, avoids the extremes of value-loaded judgements on drug use and focuses on the reduction of drug-related harm through pragmatic and low-threshold programs. This approach is likely to be important in tackling the drug problem in the 21st century. PMID:10870502
Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.

PubMed

Scott-Goodwin, A C; Puerto, M; Moreno, I

2016-06-01

Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs throughout the population. Prenatal exposure to these drugs could alter normal foetal development and could threaten future welfare. The main changes observed in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which can impede nutrient and oxygen exchange between mother and foetus, restricting foetal growth. Memory, learning processes, hearing and behaviour can also be affected. Alcohol may cause physical and cognitive alterations in prenatally exposed infants, fundamentally caused by altered NMDAR and GABAR activity. Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of activating CB1R, inducing connectivity deficits during the foetal brain development. This fact could be linked to behavioural and cognitive deficits. Many of the effects from prenatal cocaine exposure are caused by altered cell proliferation, migration, differentiation and dendritic growth processes. Cocaine causes long term behavioural and cognitive alterations and also affects the uteroplacental unit. Copyright © 2016 Elsevier Inc. All rights reserved.
Cannabis, cannabinoids, and health

PubMed Central

Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-01-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a “soft” drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (toward a higher proportion of Δ9-THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use. PMID:29302228
[Impact of internet on poisoning with psychoactive substances in young people].

PubMed

Radoniewicz-Chagowska, Anna; Tchórz, Michał; Kujawa, Anna; Szponar, Jarosław; Drelich, Grzegorz

2012-01-01

These days young people use internet as a source of information. Internet offers knowledge that can be used not only for school education but also to obtain information about usage and effects of psychoactive substances. Recent research shows that young people more often use internet websites and chat rooms to exchange knowledge and experience with chemicals and everyday products used as intoxicants, for example: nutmeg, nonprescription medications, metal cleaning liquid or feminine hygiene products. This article shows the extend of knowledge young people can gain from popular internet websites. Information on the web is presented as appealing, attractive and encouraging. From a toxicologist point of view it is extremely important to be familiar with those new threats because more and more often we have to treat young patients with a serious poisoning from usage of experimental intoxicating substances.
A systematic review of the antipsychotic properties of cannabidiol in humans.

PubMed

Iseger, Tabitha A; Bossong, Matthijs G

2015-03-01

Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia. A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system. Modulation of this system by the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia. Here we review studies that investigated the antipsychotic properties of CBD in human subjects. Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use. These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.
1-cyclohexyl-x-methoxybenzene derivatives, novel psychoactive substances seized on the internet market. Synthesis and in vivo pharmacological studies in mice.

PubMed

Fantinati, Anna; Ossato, Andrea; Bianco, Sara; Canazza, Isabella; De Giorgio, Fabio; Trapella, Claudio; Marti, Matteo

2017-05-01

Among novel psychoactive substances notified to EMCDDA and Europol were 1-cyclohexyl-x-methoxybenzene stereoisomers (ortho, meta, and para). These substances share some structural characteristics with phencyclidine and tramadol. Nowadays, no information on the pharmacological and toxicological effects evoked by 1-cyclohexyl-x-methoxybenzene are reported. The aim of this study was to investigate the effect evoked by each one stereoisomer on visual stimulation, body temperature, acute thermal pain, and motor activity in mice. Mice were evaluated in behavioral tests carried out in a consecutive manner according to the following time scheme: observation of visual placing response, measures of core body temperature, determination of acute thermal pain, and stimulated motor activity. All three stereoisomers dose-dependent inhibit visual placing response (rank order: meta > ortho > para), induce hyperthermia at lower and hypothermia at higher doses (meta > ortho > para) and cause analgesia to thermal stimuli (para > meta = ortho), while they do not alter motor activity. For the first time, this study demonstrates that systemic administration of 1-cyclohexyl-x-methoxybenzene compounds markedly inhibit visual response, promote analgesia, and induce core temperature alterations in mice. This data, although obtained in animal model, suggest their possible hazard for human health (i.e., hyperthermia and sensorimotor alterations). In particular, these novel psychoactive substances may have a negative impact in many daily activities, greatly increasing the risk factors for workplace accidents and traffic injuries. Copyright © 2017 John Wiley & Sons, Ltd.

Crisis intervention related to the use of psychoactive substances in recreational settings--evaluating the Kosmicare Project at Boom Festival.

PubMed

Carvalho, Maria Carmo; de Sousa, Mariana Pinto; Frango, Paula; Dias, Pedro; Carvalho, Joana; Rodrigues, Marta; Rodrigues, Tania

2014-01-01

Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof's psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population's views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (p<.05) confirming crisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor's profile and vulnerability to crisis showed inconclusive.
Caffeine Expectancy Questionnaire (CaffEQ): Construction, Psychometric Properties, and Associations with Caffeine Use, Caffeine Dependence, and Other Related Variables

ERIC Educational Resources Information Center

Huntley, Edward D.; Juliano, Laura M.

2012-01-01

Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of…
Familial Risk Analysis of the Association between Attention-Deficit/Hyperactivity Disorder and Psychoactive Substance Use Disorder in Female Adolescents: A Controlled Study

ERIC Educational Resources Information Center

Biederman, Joseph; Petty, Carter R.; Monuteaux, Michael C.; Mick, Eric; Clarke, Allison; Ten Haagen, Kristina; Faraone, Stephen V.

2009-01-01

Background: A robust and bi-directional comorbidity between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the…
Activated Carbon-Based System for the Disposal of Psychoactive Medications

PubMed Central

Song, Yang; Manian, Mahima; Fowler, William; Korey, Andrew; Kumar Banga, Ajay

2016-01-01

The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications. PMID:27827989
Phytocannabinoids modulate emotional memory processing through interactions with the ventral hippocampus and mesolimbic dopamine system: implications for neuropsychiatric pathology.

PubMed

Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-02-01

Growing clinical and preclinical evidence suggests a potential role for the phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is associated with acute and neurodevelopmental propsychotic side effects through its interaction with central cannabinoid type 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus (VHipp) potentiates affective memory formation through inputs to the mesolimbic dopamine (DA) system, thereby altering emotional salience attribution. These changes in DA activity and salience attribution, evoked by dysfunctional VHipp regulatory actions and THC exposure, could predispose susceptible individuals to psychotic symptoms. Although THC can accelerate the onset of schizophrenia, CBD displays antipsychotic properties, can prevent the acquisition of emotionally irrelevant memories, and reverses amphetamine-induced neuronal sensitization through selective phosphorylation of the mechanistic target of rapamycin (mTOR) molecular signaling pathway. This review summarizes clinical and preclinical evidence demonstrating that distinct phytocannabinoids act within the VHipp and associated corticolimbic structures to modulate emotional memory processing through changes in mesolimbic DA activity states, salience attribution, and signal transduction pathways associated with schizophrenia-related pathology.
Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E ("Europa").

PubMed

Sacks, Justin; Ray, M Jordan; Williams, Sue; Opatowsky, Michael J

2012-10-01

We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or "Europa." Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer "designer" psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We describe magnetic resonance imaging (MRI) findings to include selective diffuse toxic injury of the cerebral white matter with sparing of the cortex and most of the deep gray nuclei. To our knowledge, this is the first reported description of cerebral findings on MRI that are likely related to a lethal ingestion of 2C-E.
Analysis of new psychoactive substances in human urine by ultra-high performance supercritical fluid and liquid chromatography: Validation and comparison.

PubMed

Borovcová, Lucie; Pauk, Volodymyr; Lemr, Karel

2018-05-01

New psychoactive substances represent serious social and health problem as tens of new compounds are detected in Europe annually. They often show structural proximity or even isomerism, which complicates their analysis. Two methods based on ultra high performance supercritical fluid chromatography and ultra high performance liquid chromatography with mass spectrometric detection were validated and compared. A simple dilute-filter-and-shoot protocol utilizing propan-2-ol or methanol for supercritical fluid or liquid chromatography, respectively, was proposed to detect and quantify 15 cathinones and phenethylamines in human urine. Both methods offered fast separation (<3 min) and short total analysis time. Precision was well <15% with a few exceptions in liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3 ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography. Nevertheless, this technique distinguished all analytes including four pairs of isomers, while liquid chromatography was unable to resolve fluoromethcathinone regioisomers. Concerning matrix effects and recoveries, supercritical fluid chromatography produced more uniform results for different compounds and at different concentration levels. This work demonstrates the performance and reliability of supercritical fluid chromatography and corroborates its applicability as an alternative tool for analysis of new psychoactive substances in biological matrixes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[Self-Reported consumption of illegal psychoactive substances in a street inhabitant population from Cali, Colombia].

PubMed

Hernández-Carrillo, Mauricio; Álvarez-Claros, Katherine E; Osorio-Sabogal, Iván Alberto

2015-04-01

Objective To determine the prevalence of self-reported use of illegal psychoactive substances in a homeless population of the city of Cali. Method Descriptive study of prevalence of period. The target population was 763 homeless people registered during 2010 in the database provided by a temporary shelter facility in the city of Cali. Statistical analysis was performed using R version 3.2.0. Research safe according to the resolution 8430 of 1993. Results 76.9 % of the homeless population recognizes that they consume some type of illegal psychoactive substance (IPAS). The substances with a higher prevalence of use in this population were: marijuana (51.2 %), the crack cocaine (44.6 %) and cocaine (11.3 %). 28.6 % of homeless people were found to consume IPAS more than three times a day and that the main route of administration is smoke (54.7 %). 50% of respondents reported having been hospitalized at some time in a rehabilitation center. Discussion The results in this study show that the problem of PASI consumption significantly affects the population of homeless people, with marijuana and crack cocaine being the most commonly used, which is a complex situation if the easy access of these substances and the severe physical and mental degenerative effects the cause in those who consume them are taken into account. Therefore it is necessary to support initiatives aimed at intervening in this social phenomenon.
Valproate for agitation in critically ill patients: A retrospective study.

PubMed

Gagnon, David J; Fontaine, Gabriel V; Smith, Kathryn E; Riker, Richard R; Miller, Russell R; Lerwick, Patricia A; Lucas, F L; Dziodzio, John T; Sihler, Kristen C; Fraser, Gilles L

2017-02-01

The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium. This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models. Fifty-three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (-185 μg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects. Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation. Copyright © 2016 Elsevier Inc. All rights reserved.
Therapeutic potential of cannabis in pain medicine.

PubMed

Hosking, R D; Zajicek, J P

2008-07-01

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.
In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.

PubMed

Fisher, T; Golan, H; Schiby, G; PriChen, S; Smoum, R; Moshe, I; Peshes-Yaloz, N; Castiel, A; Waldman, D; Gallily, R; Mechoulam, R; Toren, A

2016-03-01

Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells. Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts. Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.
In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma

PubMed Central

Fisher, T.; Golan, H.; Schiby, G.; PriChen, S.; Smoum, R.; Moshe, I.; Peshes-Yaloz, N.; Castiel, A.; Waldman, D.; Gallily, R.; Mechoulam, R.; Toren, A.

2016-01-01

Background Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. Methods We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ9-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells. Results Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts. Conclusions Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl. PMID:27022310
Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells.

PubMed

Iuvone, Teresa; Esposito, Giuseppe; Esposito, Ramona; Santamaria, Rita; Di Rosa, Massimo; Izzo, Angelo A

2004-04-01

Abstract Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on beta-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to beta-amyloid peptide (1 micro g/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against beta-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.
The Great Irish Head Shop Controversy

ERIC Educational Resources Information Center

Ryall, Graham; Butler, Shane

2011-01-01

This research describes and analyses recent policy developments in Ireland in relation to the practice of selling psychoactive substances which, while not themselves illegal, mimic the effects of commonly used illegal drugs. These so-called "legal highs" had been sold in Ireland through an increasing number of "head shops"…
Effects of Substance Use Education Programs: A Cross-Cultural Comparison of Student Use.

ERIC Educational Resources Information Center

Venuti, John Paul; Chambliss, Catherine

In this study, differential substance use between American and Australian college students was assessed through administration of a survey concerning recent use of six commonly used psychoactive substances (cigarettes, chewing tobacco, alcohol, marijuana, cocaine, and caffeine). Situational contexts associated with the use of each particular…
Effects of Substance Use Education Programs: Gender Differences in Student Substance Use.

ERIC Educational Resources Information Center

Venuti, John Paul; Conroy, Matthew; Landis, Pamela; Chambliss, Catherine

This study assesses the differential substance use between male and female college students through the administration of a survey of recent use of six commonly used psychoactive substances (cigarettes, chewing tobacco, alcohol, marijuana, cocaine, and caffeine). It investigates the situational contexts associated with use of particular substances…
Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials.

PubMed

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-08-01

To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.
Efficacy and adverse effects of medical marijuana for chronic noncancer pain

PubMed Central

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-01-01

Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP. PMID:26505059
[Consumption of psychoactive substances by caregivers].

PubMed

Gauthier, Françoise

2012-11-01

Prescribed medication, self-medication or doping the use of psychoactive substances by caregivers is varied. Doping behaviour in the care environment is under-estimated and trivialised. It is often difficult to spot at an early stage and yet this consumption is not without consequences on the quality and safety of work. Gérard-Marchant general hospital in Toulouse integrates this issue into its professional risk management policy.
An Expanding World of Novel Psychoactive Substances: Opioids

PubMed Central

Zawilska, Jolanta B.

2017-01-01

The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e.g., acetylfentanyl, acryloylfentanyl, carfentanil, α-methylfentanyl, 3-methylfentanyl, furanylfentanyl, 4-fluorobutyrylfentanyl, 4-methoxybutyrylfentanyl, 4-chloroisobutyrylfentanyl, 4-fluoroisobutyrylfentanyl, tetrahydrofuranylfentanyl, cyclopentylfentanyl, and ocfentanil) and compounds with different chemical structures, such as AH-7921, MT-45, and U-47700. This survey provides an overview of the pharmacological properties, pattern of use, and desired and unwanted effects of the above-listed novel opioids. Special emphasis is given to cases of non-fatal and lethal intoxication involving these compounds. PMID:28713291

New psychoactive substances: catalysing a shift in forensic science practice?

PubMed

Tettey, Justice; Crean, Conor

2015-08-05

The analysis of substances of abuse remains one of the most matured areas in forensic science with a strong scientific basis, namely analytical chemistry. The current evolving drug markets, characterized by the global emergence of new psychoactive substances (NPS) and the need for forensic scientists to identify an unprecedented and ever-increasing number of NPS, presents a unique challenge to this discipline. This article looks at the current situation with NPS at the global level, and the challenges posed to the otherwise technically robust forensic science discipline of analysis of substances of abuse. It discusses the preparedness of forensic science to deal with the current situation and identifies the need for a shift in forensic science practice, especially one which embraces research and looks beyond normal casework in order to provide the much needed data for developing effective policy responses to the NPS problem. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
[Psychosocial correlations of the experimentation with psychoactive substances in Spanish teenagers].

PubMed

de la Villa Moral, María; Javier Rodríguez, Francisco; Ovejero, Anastasio

2010-01-01

To offer an analysis of the factors that determine the consumption of psychoactive substances by youth and to evaluate the predictive capacity of variables related to attitude, affect, the family and groups, as well as academics, among others. A sample of 750 adolescents was selected at the Principado de Asturias (Spain) (mode 15 years of age, mean=14.69) enrolled during the 2008-2009 academic year. It was confirmed that the teenagers who consumed alcohol and other drugs present a differential profile as compared to non-consumers with respect to greater attitudinal permissiveness, effect of paternal modelling and peer groups, institutional dissatisfaction, emotional instability, and manifestation of more disruptive conducts with problems relating to others and attention-seeking. From our ethiological model we conclude that the consumption of drugs by youth is determined by an interrelation of personal, familiar, school and psychosocial variables.
MDMA: interactions with other psychoactive drugs.

PubMed

Mohamed, Wael M Y; Ben Hamida, Sami; Cassel, Jean-Christophe; de Vasconcelos, Anne Pereira; Jones, Byron C

2011-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments, MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents. Copyright © 2011 Elsevier B.V. All rights reserved.
Psychoactive substance use by truck drivers: a systematic review

PubMed Central

Girotto, Edmarlon; Mesas, Arthur Eumann; de Andrade, Selma Maffei; Birolim, Marcela Maria

2014-01-01

The aim of this study was to summarise the scientific evidence on the prevalence of psychoactive substance use and on the factors associated with their intake among truck drivers. A systematic review was performed in the databases PubMed, Scientific Electronic Library Online, Latin American and Caribbean Health Sciences, and Cochrane and 36 cross-sectional studies were identified with quantitative results about the use of psychoactive substances by truck drivers. Out of these, 28 were carried out in countries with large land areas and 23 obtained their information through self-reporting. The most frequently studied substances were alcohol (n=25), amphetamines (n=17), marijuana (n=16) and cocaine (n=13). The prevalence of the use of these substances greatly varied: alcohol (0.1–91.0%); amphetamines (0.2–82.5%), marijuana (0.2–29.9%), cocaine (0.1–8.3%). The frequency of substance use was lower in studies that investigated the presence of these substances in biological samples than in those based on self-reported use. In 12 studies that evaluated factors associated with the intake of psychoactive substances, the following stood out: younger age, higher income, longer trips, alcohol consumption, driving in the night shift, travelling interstate routes, long or short sleep, fewer hours of rest, little experience of the driver, connection with small and medium sized companies, income below levels determined by labour agreements, productivity-based earnings and prior involvement in accidents. The frequency of psychoactive substance use by truck drivers seems to be high, although that greatly varies according to the type of substance and the method of collecting the information. The use of these substances was mainly associated with indicators of poor working conditions. PMID:24145953
Conditional substance abuse and dependence by diagnosis of mood or anxiety disorder or schizophrenia in the U.S. population.

PubMed

Martins, Silvia S; Gorelick, David A

2011-12-01

Little is known about the association of various psychiatric disorders with the risk of developing dependence or abuse among users of various psychoactive substances (conditional dependence, CD; conditional abuse, CA). Evaluate the association of psychiatric disorders with CA only, CD only and CA+CD. Secondary analysis of data from 43,093 non-institutionalized US adults in the first wave (2001-2002) of the National Epidemiological Survey on Alcohol and Related Conditions. A structured diagnostic interview allowed classification by lifetime psychiatric diagnosis (DSM-IV criteria) and psychoactive substance use. Data were analyzed using weighted proportions, 95% CIs, and weighted logistic regression models to generate odds ratios (OR) adjusted for socio-demographic characteristics. Psychiatric disorders were associated with higher prevalence of psychoactive substance use, regardless of type of disorder or substance. CA, CD and CA+CD prevalence rates were generally higher than unconditional prevalence rates among respondents with and without psychiatric disorders. Respondents with multiple disorders (mainly mood and anxiety disorders) had higher rates of CA+CD on most, but not all, psychoactive substances (e.g., not heroin), while schizophrenia was associated only with higher rates of tranquilizer CA+CD. Psychiatric disorders had few associations with CA only and CD only on psychoactive substances. Study findings suggest that mood and anxiety disorders are associated with increased prevalence of substance use and increased transition from use to CA and CD, while schizophrenia is associated with increased transition from abstinence to use, especially for marijuana. Findings did not support the self-medication hypothesis of substance use disorders. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Conditional substance abuse and dependence by diagnosis of mood or anxiety disorder or schizophrenia in the U.S. population

PubMed Central

Martins, Silvia S.; Gorelick, David A.

2011-01-01

Background Little is known about the association of various psychiatric disorders with the risk of developing dependence or abuse among users of various psychoactive substances (conditional dependence, CD; conditional abuse, CA). Objectives Evaluate the association of psychiatric disorders with CA only, CD only and CA +CD. Method Secondary analysis of data from 43,093 non-institutionalized US adults in the first wave (2001–2002) of the National Epidemiological Survey on Alcohol and Related Conditions. A structured diagnostic interview allowed classification by lifetime psychiatric diagnosis (DSM-IV criteria) and psychoactive substance use. Data were analyzed using weighted proportions, 95% CIs, and weighted logistic regression models to generate odds ratios (OR) adjusted for socio-demographic characteristics. Results Psychiatric disorders were associated with higher prevalence of psychoactive substance use, regardless of type of disorder or substance. CA, CD and CA+ CD prevalence rates were generally higher than unconditional prevalence rates among respondents with and without psychiatric disorders. Respondents with multiple disorders (mainly mood and anxiety disorders) had higher rates of CA+CD on most, but not all, psychoactive substances (e.g., not heroin), while schizophrenia was associated only with higher rates of tranquilizer CA+ CD. Psychiatric disorders had few associations with CA only and CD only on psychoactive substances. Conclusion Study findings suggest that mood and anxiety disorders are associated with increased prevalence of substance use and increased transition from use to CA and CD, while schizophrenia is associated with increased transition from abstinence to use, especially for marijuana. Findings did not support the self-medication hypothesis of substance use disorders. PMID:21641123
Non-medical use of psychoactive drugs in relation to suicide tendencies among Chinese adolescents.

PubMed

Juan, Wang; Jian-Xiong, Deng; Lan, Guo; Yuan, He; Xue, Gao; Jing-Hui, Huang; Guo-Liang, Huang; Ci-Yong, Lu

2015-12-01

To investigate the prevalence of non-medical use of psychoactive prescription drug (NMUPD) among adolescents and to explore the associations between non-medical psychoactive prescription drug use and depressive symptoms, poor sleep quality, deliberate self-harm, and suicide. A two-stage stratified cluster sample design produced a representative sample of 12-19-year-old students in grades 1-6 who attended public middle schools in Guangdong province. Prevalence estimates (SE) of non-medical psychoactive prescription drug use were calculated, and logistic regression was used to examine its association with depressive symptoms, poor sleep quality, deliberate self-harm, and suicide. Overall, 7.5% of adolescents reported non-medical use of opioids, and 4.8% of adolescents reported non-medical use of sedatives. Lifetime, last-year, and last-month non-medical use of opioids and sedatives were positively associated with depressive symptoms, poor sleep quality, deliberate self-harm, suicidal ideation, and suicidal attempts among different gender and age-group adolescents. Those who reported last month non-medical use of opioids and sedatives had the greatest odds of reporting depressive symptoms, poor sleep quality, deliberate self-harm, suicidal ideation, and suicidal attempts. Males who were last month non-medical users of opioids or sedative had 8.9 or 10.7 times greater odds of reporting a suicidal attempt, and 8.8 or 9.8 times greater odds of reporting a suicidal attempt were observed among adolescents aged 16-19 who were last-month non-medical users of opioids or sedatives. These findings provide evidence for improving adolescents' suicide prevention strategy by targeting supervision on high risk current non-medical users of psychoactive drug. Copyright © 2015 Elsevier Ltd. All rights reserved.
Sex and age differences in ED patients with mental and behavioral disorders due to psychoactive substance use.

PubMed

Le Querrec, Fanny; Bounes, Vincent; Mestre, Maryse Lapeyre; Azema, Olivier; Longeaux, Nicolas; Gallart, Jean-Christophe

2015-11-01

The objectives of this study are to describe an emergency department (ED) adult population with the chief complaint of mental and behavioral disorders due to psychoactive substance use and to investigate sex- and age-related differences. We analyzed data (2009-2011) from the Regional Observatory of Emergency Medicine ORU-MiP (700000 patients per year) for all patients with a primary diagnosis of mental and behavioral disorders due to psychoactive substance use. Day data were weighted by the number of days in the year and expressed for 100000 inhabitants of the area. Pearson χ(2) test and Fisher tests were used. The Brown-Mood test was used to compare medians. Of the 1411597 ED visits analyzed, 20838 consults (1.3%) were for primary diagnosis of mental and behavioral disorders due to psychoactive substance use. The median age (interquartile range) was 41 (28-51) years; 69.5% were men. More women consulted the ED for sedative or hypnotic use (4.9% vs 1.5%, P < 10(-4)) than men, and more men consulted for alcohol consumption (93.5% vs 90%, P < 10(-4)) and cannabinoids (1.4% vs 1.0%, P < 10(-3)) than women. Young consumer visits dramatically increased during weekends (average of 88 visits a day per 100000 inhabitants vs 34 on Mondays to Thursdays). Another difference was found between young adults and middle-aged adults, with a peak in visits at 2 am and 9 pm respectively. Mental and behavioral disorders due to psychoactive substance use account for 1.3% of ED visits. Older people should be screened for chronic alcohol consumption. Our findings underscore the opportunity provided by the ED for screening and brief intervention in drug- and alcohol-related problems. Copyright © 2015 Elsevier Inc. All rights reserved.
Psychoactive substance use by truck drivers: a systematic review.

PubMed

Girotto, Edmarlon; Mesas, Arthur Eumann; de Andrade, Selma Maffei; Birolim, Marcela Maria

2014-01-01

The aim of this study was to summarise the scientific evidence on the prevalence of psychoactive substance use and on the factors associated with their intake among truck drivers. A systematic review was performed in the databases PubMed, Scientific Electronic Library Online, Latin American and Caribbean Health Sciences, and Cochrane and 36 cross-sectional studies were identified with quantitative results about the use of psychoactive substances by truck drivers. Out of these, 28 were carried out in countries with large land areas and 23 obtained their information through self-reporting. The most frequently studied substances were alcohol (n=25), amphetamines (n=17), marijuana (n=16) and cocaine (n=13). The prevalence of the use of these substances greatly varied: alcohol (0.1-91.0%); amphetamines (0.2-82.5%), marijuana (0.2-29.9%), cocaine (0.1-8.3%). The frequency of substance use was lower in studies that investigated the presence of these substances in biological samples than in those based on self-reported use. In 12 studies that evaluated factors associated with the intake of psychoactive substances, the following stood out: younger age, higher income, longer trips, alcohol consumption, driving in the night shift, travelling interstate routes, long or short sleep, fewer hours of rest, little experience of the driver, connection with small and medium sized companies, income below levels determined by labour agreements, productivity-based earnings and prior involvement in accidents. The frequency of psychoactive substance use by truck drivers seems to be high, although that greatly varies according to the type of substance and the method of collecting the information. The use of these substances was mainly associated with indicators of poor working conditions.
[Addictions and the workplace: what are the issues at stake for occupational health services?].

PubMed

Durand, Eric

2008-01-01

The existing high prevalence and increase in the consumption of psychoactive substances among active employees in the workforce has created a new challenge for occupational health services. Addressing the issue of addictions in the workplace environment remains delicate due to the regulation stating that "the purpose of occupational medicine is essentially preventative, i.e., to prevent any deterioration in health due to work". Discussions have primarily focused on screening for psychoactive substances, whose use may have potential negative and damaging consequences on a workers aptitude and capability to perform. A descriptive inventory gathered from results of research carried out on the situation of psychoactive substance consumption among workers precedes a presentation of prevention tools currently available to companies and occupational health services. Ethical and legal aspects of their implementation and use are discussed.
[Risk and protection factors related to the consumption of psychoactive substances in undergraduate nursing students].

PubMed

Morales, Blanca Nivia; Plazas, Merideidy; Sanchez, Rafael; Ventura, Carla Aparecida Arena

2011-06-01

This study aims to identify the frequency of risk and protection factors related to drug consumption among undergraduate nursing students. It is a cross-sectional study in which authors applied the instrument Risk and Protection Factors for the Consumption of Psychoactive Substances, validated for use with undergraduate nursing students. Data were analyzed through STATA 10. Three hundred and ninety students participated in the study. The domain "prejudice and appraisal", "social permissiveness and access to psychoactive substances", "social skills and self-control" are risk factors for drugs use in 100% of participants. "Spirituality" and "satisfaction with interpersonal relations" were predominant protective domains. Based on data, authors can conclude that the students did not consider the risks in alcohol and tobacco consumption, as they think it is normal and socially acceptable.
In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks.

PubMed

Wagmann, Lea; Brandt, Simon D; Kavanagh, Pierce V; Maurer, Hans H; Meyer, Markus R

2017-04-15

Tryptamines have emerged as new psychoactive substances (NPS), which are distributed and consumed recreationally without preclinical studies or safety tests. Within the alpha-methylated tryptamines, some of the psychoactive effects of the prototypical alpha-methyltryptamine (AMT) have been described decades ago and a contributing factor of its acute toxicity appears to involve the inhibition of monoamine oxidase (MAO). However, detailed information about analogs is scarce. Therefore, thirteen AMT analogs were investigated for their potential to inhibit MAO. An in vitro assay analyzed using hydrophilic interaction liquid chromatography-high resolution-tandem mass spectrometry was developed and validated. The AMT analogs were incubated with recombinant human MAO-A or B and kynuramine, a non-selective MAO substrate to determine the IC 50 values. The known MAO-A inhibitors 5-(2-aminopropyl)indole (5-IT), harmine, harmaline, yohimbine, and the MAO-B inhibitor selegiline were tested for comparison. AMT and all analogs showed MAO-A inhibition properties with IC 50 values between 0.049 and 166μM, whereas four analogs inhibited also MAO-B with IC 50 values between 82 and 376μM. 7-Me-AMT provided the lowest IC 50 value against MAO-A comparable to harmine and harmaline and was identified as a competitive MAO-A inhibitor. Furthermore, AMT, 7-Me-AMT, and nine further analogs inhibited MAO activity in human hepatic S9 fraction used as model for the human liver which expresses both isoforms. The obtained results suggested that MAO inhibition induced by alpha-methylated tryptamines might be clinically relevant concerning possible serotonergic and adrenergic effects and interactions with drugs (of abuse) particularly acting as monoamine reuptake inhibitors. However, as in vitro assays have only limited conclusiveness, further studies are needed. Copyright © 2017 Elsevier B.V. All rights reserved.
Hair analysis for the detection of drug use-is there potential for evasion?

PubMed

Marrinan, Shanna; Roman-Urrestarazu, Andres; Naughton, Declan; Levari, Emerlinda; Collins, John; Chilcott, Robert; Bersani, Giuseppe; Corazza, Ornella

2017-05-01

Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques. Copyright © 2017 John Wiley & Sons, Ltd.
The Endocannabinoid System as a Target for Treatment of Breast Cancer

DTIC Science & Technology

2010-08-01

psychoactive constituent of marijuana (Gaoni and Mechoulam, 1964), as well as other naturally occurring and synthetically derived cannabinoids bind to and...the primary psychoactive constituent present in marijuana , and WIN55,212-2, a highly potent, full CB1 receptor agonist. Female mice implanted with...potent and highly efficacious synthetic cannabinoid receptor agonist originally developed as a nonsteroidal anti-inflammatory drug (Ward et al., 1991
Professional Attitudes of the Teachers in Implementation of a School-Based Programme about Prevention of the Use Psychoactive Substances in 5-7 Grade

ERIC Educational Resources Information Center

Kozhuharova, Penka Petkova

2015-01-01

The subject of the research is the planning, implementation and evaluation of the program about prevention of the use of psychoactive substances among students 5-7 grade. The study was conducted by survey method with 314 teachers who teach in twenty-six schools. The qualification of the teachers to work with the program about prevention was…
Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones.

PubMed

Patrick, Megan E; O'Malley, Patrick M; Kloska, Deborah D; Schulenberg, John E; Johnston, Lloyd D; Miech, Richard A; Bachman, Jerald G

2016-09-01

The current study documents the characteristics associated with the use of two novel psychoactive substances: synthetic cannabinoids and synthetic cathinones. Nationally representative samples of students in 8th (n = 9665), 10th (n = 10 655) and 12th (n = 10 057) grades across the US were included in the Monitoring the Future study from 2012 to 2014. There were relatively few differences in prevalence based on sociodemographic characteristics, although boys were at greater risk for use of synthetic cannabinoids in 12th grade (used by 10.3% of boys and 6.4% of girls) and for use of synthetic cathinones in 10th grade (used by 1.0% of boys and 0.4% of girls). Synthetic drug use was also associated with truancy and use of cigarettes, alcohol, and marijuana. Prevention and intervention efforts for novel psychoactive substance use should focus primarily on polysubstance users and youth who are disengaged from school.[Patrick M, O'Malley P, Kloska D, Schulenberg J, Johnston L, Miech R, Bachman J. Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones. Drug Alcohol Rev 2016;35:586-590]. © 2015 Australasian Professional Society on Alcohol and other Drugs.
Effectiveness of a universal internet-based prevention program for ecstasy and new psychoactive substances: a cluster randomized controlled trial.

PubMed

Champion, Katrina E; Newton, Nicola C; Stapinski, Lexine A; Teesson, Maree

2016-08-01

To evaluate the effectiveness of an online school-based prevention program for ecstasy (MDMA) and new psychoactive substances (NPS). Cluster randomized controlled trial with two groups (intervention and control). Eleven secondary schools in Australia. A total of 1126 students (mean age: 14.9 years). The internet-based Climate Schools: Ecstasy and Emerging Drugs module uses cartoon storylines to convey information about harmful drug use. It was delivered once weekly, during a 4-week period, during health education classes. Control schools received health education as usual. Primary outcomes were self-reported intentions to use ecstasy and NPS at 12 months. Secondary outcomes were ecstasy and NPS knowledge and life-time use of ecstasy and NPS. Surveys were administered at baseline, post-intervention and 6 and 12 month post-baseline. At 12 months, the proportion of students likely to use NPS was significantly greater in the control group (1.8%) than the intervention group [0.5%; odds ratio (OR) = 10.17, 95% confidence interval (CI) = 1.31-78.91]. However, students' intentions to use ecstasy did not differ significantly between groups (control = 2.1%, intervention = 1.6%; OR = 5.91, 95% CI = 1.01-34.73). There was a significant group difference in the change from baseline to post-test for NPS knowledge (β = -0.42, 95% CI = -0.62 to -0.21, Cohen's d = 0.77), with controls [mean = 2.78, standard deviation (SD = 1.48] scoring lower than intervention students (mean = 3.85, SD = 1.49). There was also evidence of a significant group difference in ecstasy knowledge at post-test (control: mean = 9.57, SD = 3.31; intervention: mean = 11.57, SD = 3.61; β = -0.54, 95% CI = -0.97 to -0.12, P = 0.01, d = 0.73). The Climate Schools: Ecstasy and Emerging Drugs module, a universal online school-based prevention program, appeared to reduce students' intentions to use new psychoactive substances and increased knowledge about ecstasy and new psychoactive substances in the short term. © 2016 Society for the Study of Addiction.
Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness.

PubMed

Hamill, Jonathan; Hallak, Jaime; Dursun, Serdar M; Baker, Glen

2018-01-24

Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience. More recently it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation. To review ayahuasca's behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness. We searched Medline, in English, using the terms ayahuasca, dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications. The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects, safety and adverse effects; pharmacology; potential psychiatric uses. Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and many present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers feel that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized credible researchers to conduct comprehensive clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
75 FR 4400 - Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... comments on the draft guidance by March 29, 2010. ADDRESSES: Submit written requests for single copies of...] Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability AGENCY: Food and... psychoactive effects such as sedation, euphoria, or mood change. DATES: Although you can comment on any...
Facts on Nicotine and Tobacco. Clearinghouse Fact Sheet.

ERIC Educational Resources Information Center

Slade, John

Nicotine, the most abused drug in the United States, is the psychoactive drug in tobacco. It exerts diverse, often subtle effects on the central nervous system and can stimulate or relax, or do both simultaneously. Tolerance to this drug develops easily and addiction is common among people with other drug problems, especially alcoholism. Most…

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-07-08

Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.
Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

PubMed Central

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-01-01

Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349
Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.

PubMed

Verhoeckx, Kitty C M; Korthout, Henrie A A J; van Meeteren-Kreikamp, A P; Ehlert, Karl A; Wang, Mei; van der Greef, Jan; Rodenburg, Richard J T; Witkamp, Renger F

2006-04-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.
Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A.

PubMed

Moreno-Sanz, Guillermo

2016-01-01

Δ 9 -tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ 9 -tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa . THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term "THCA" to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.
Drugs of Abuse and Novel Psychoactive Substances at Outdoor Music Festivals in Colorado

PubMed Central

Fox, Jacob; Smith, Alexis; Yale, Alexander; Chow, Christopher; Alaswad, Elsa; Cushing, Tracy; Monte, Andrew A.

2017-01-01

Background Drugs of abuse (DOA) are widely used in the United States and are ubiquitous at outdoor music festivals. Attendees at music festivals are at high-risk for novel psychoactive substance (NPS) use, which is becoming more prevalent worldwide. No U.S. studies have employed an qualitative approach to investigate the etiologies of both traditional DOA and NPS use amongst music festival attendees. Objectives The objective of this study was to improve understanding of the knowledge, attitudes, beliefs, and practices of festival attendees using NPS and DOA. Methods We conducted semi-structured interviews of 171 attendees during the Sonic Bloom and Arise music festivals in Colorado in 2015 and 2016. Discrete variables were summarized with descriptive statistics. The anonymous, multi-domain interview documented the knowledge, attitudes beliefs, and practices underlying DOA use, which were analyzed with qualitative methods. Results We enrolled 171 participants that endorsed DOA use at the festivals. Most were experienced DOA users, who perceived minimal risks associated with DOA and NPS use. Nearly all unanimously reported normalization of DOA at music festivals. Participants popularly cited empathogenic, entactogenic, and entheogenic effects of DOA as their primary motivations for use. NPS use was endorsed by 39.8% (n = 68) of respondents, all of whom identified as being experienced DOA users. Conclusions This population of novel psychoactive substance users is primarily composed of experienced drug users that endorsed use because of low cost, minimal perceived risk, accessibility, and normalization of drug use at music festivals. PMID:29148866
Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs.

PubMed

Hassan, Zurina; Bosch, Oliver G; Singh, Darshan; Narayanan, Suresh; Kasinather, B Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B; Müller, Christian P

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.
Drugs of Abuse and Novel Psychoactive Substances at Outdoor Music Festivals in Colorado.

PubMed

Fox, Jacob; Smith, Alexis; Yale, Alexander; Chow, Christopher; Alaswad, Elsa; Cushing, Tracy; Monte, Andrew A

2018-06-07

Drugs of abuse (DOA) are widely used in the United States and are ubiquitous at outdoor music festivals. Attendees at music festivals are at high-risk for novel psychoactive substance (NPS) use, which is becoming more prevalent worldwide. No U.S. studies have employed an qualitative approach to investigate the etiologies of both traditional DOA and NPS use amongst music festival attendees. The objective of this study was to improve understanding of the knowledge, attitudes, beliefs, and practices of festival attendees using NPS and DOA. We conducted semi-structured interviews of 171 attendees during the Sonic Bloom and Arise music festivals in Colorado in 2015 and 2016. Discrete variables were summarized with descriptive statistics. The anonymous, multi-domain interview documented the knowledge, attitudes beliefs, and practices underlying DOA use, which were analyzed with qualitative methods. We enrolled 171 participants that endorsed DOA use at the festivals. Most were experienced DOA users, who perceived minimal risks associated with DOA and NPS use. Nearly all unanimously reported normalization of DOA at music festivals. Participants popularly cited empathogenic, entactogenic, and entheogenic effects of DOA as their primary motivations for use. NPS use was endorsed by 39.8% (n = 68) of respondents, all of whom identified as being experienced DOA users. This population of novel psychoactive substance users is primarily composed of experienced drug users that endorsed use because of low cost, minimal perceived risk, accessibility, and normalization of drug use at music festivals.
New challenges and innovation in forensic toxicology: focus on the "New Psychoactive Substances".

PubMed

Favretto, Donata; Pascali, Jennifer P; Tagliaro, Franco

2013-04-26

In the recent years, new molecules have appeared in the illicit market, claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects; this heterogeneous and rapidly evolving class of compounds are commonly known as "New Psychoactive Substances" or, less properly, "Smart Drugs" and are easily distributed through the e-commerce or in the so-called "Smart Shops". They include, among other, synthetic cannabinoids, cathinones and tryptamine analogs of psylocin. Whereas cases of intoxication and death have been reported, the phenomenon appears to be largely underestimated and is a matter of concern for Public Health. One of the major points of concern depends on the substantial ineffectiveness of the current methods of toxicological screening of biological samples to identify the new compounds entering the market. These limitations emphasize an urgent need to increase the screening capabilities of the toxicology laboratories, and to develop rapid, versatile yet specific assays able to identify new molecules. The most recent advances in mass spectrometry technology, introducing instruments capable of detecting hundreds of compounds at nanomolar concentrations, are expected to give a fundamental contribution to broaden the diagnostic spectrum of the toxicological screening to include not only all these continuously changing molecules but also their metabolites. In the present paper a critical overview of the opportunities, strengths and limitations of some of the newest analytical approaches is provided, with a particular attention to liquid phase separation techniques coupled to high accuracy, high resolution mass spectrometry. Copyright © 2012 Elsevier B.V. All rights reserved.
Worldwide legislative challenges related to psychoactive drugs.

PubMed

Negrei, Carolina; Galateanu, Bianca; Stan, Miriana; Balalau, Cristian; Dumitru, Mircea Lucian Bogdan; Ozcagli, Eren; Fenga, Concettina; Kovatsi, Leda; Fragou, Domniki; Tsatsakis, Aristidis

2017-06-02

The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.
Guilty by dissociation-development of gas chromatography-mass spectrometry (GC-MS) and other rapid screening methods for the analysis of 13 diphenidine-derived new psychoactive substances (NPSs).

PubMed

Geyer, Pierre M; Hulme, Matthew C; Irving, Joseph P B; Thompson, Paul D; Ashton, Ryan N; Lee, Robert J; Johnson, Lucy; Marron, Jack; Banks, Craig E; Sutcliffe, Oliver B

2016-11-01

The prevalence of new psychoactive substances (NPSs) in forensic casework has increased prominently in recent years. This has given rise to significant legal and analytical challenges in the identification of these substances. The requirement for validated, robust and rapid testing methodologies for these compounds is obvious. This study details the analysis of 13 synthesised diphenidine derivatives encountered in casework using presumptive testing, thin layer chromatography and gas chromatography-mass spectrometry (GC-MS). Specifically, the validated GC-MS method provides, for the first time, both a general screening method and quantification of the active components for seized solid samples, both in their pure form and in the presence of common adulterants. Graphical Abstract Chemical synthesis and forensic analysis of 13 diphenidine-derived new psychoactive substance(s).
Tea component, epigallocatechin gallate, potentiates anticataleptic and locomotor-sensitizing effects of caffeine in mice.

PubMed

Kasture, Sanjay B; Gaikar, Mayur; Kasture, Veena; Arote, Sanjay; Salve, Balu; Rosas, Michela; Cotti, Elisabetta; Acquas, Elio

2015-02-01

Tea is the most popular beverage worldwide. Caffeine, the psychoactive principle of tea, pharmacologically interacts with several drugs and bioactive molecules. Epigallocatechin gallate (EGCG) is a major component of tea and its known interactions with caffeine make it worthwhile to further study them by investigating the influence of EGCG on the anticataleptic and locomotor-sensitizing effects of caffeine. In the present investigation, we observed that (a) administration of caffeine or EGCG alone inhibited haloperidol-induced catalepsy, a widely used animal model to study parkinsonism, and (b) a combination of caffeine and EGCG produced greater inhibition of haloperidol-induced catalepsy. Furthermore, after repeated administration of caffeine and EGCG, either alone or in combination, we observed that (c) caffeine and EGCG contrasted the sensitization of catalepsy observed after repeated haloperidol administration by significantly reducing the duration of catalepsy. Furthermore, as haloperidol-induced catalepsy was also associated with increased lipid peroxidation, we observed that (d) EGCG administration reduced striatal lipid peroxide levels in a dose-dependent manner and that (e) the combination of caffeine with EGCG was most effective in reducing haloperidol-increased striatal lipid peroxide. Finally, we observed that (f) chronic caffeine and EGCG significantly elicited locomotor sensitization and that (g) their combination resulted in significantly greater effects. In conclusion, EGCG potentiated the effects of caffeine on haloperidol-induced catalepsy and of caffeine-elicited locomotor sensitization. Overall, these observations indicate critical interactions between caffeine and EGCG in an animal model of parkinsonism and locomotor activity and suggest that tea consumption might reduce antipsychotic-induced side effects.
N,N-Dimethyltryptamine and dichloromethane: rearrangement of quaternary ammonium salt product during GC-EI and CI-MS-MS analysis.

PubMed

Brandt, Simon D; Martins, Cláudia P B; Freeman, Sally; Dempster, Nicola; Wainwright, Mark; Riby, Philip G; Alder, John F

2008-05-12

N,N-Dimethyltryptamine (DMT) 1 is a simple tryptamine derivative with powerful psychoactive properties. It is abundant in nature and easily accessible through a variety of synthetic routes. Most work-up procedures require the use of organic solvents and halogenated representatives are often employed. DMT was found to be reactive towards dichloromethane, either during work-up or long term storage therein, which led to the formation of the quaternary ammonium salt N-chloromethyl-DMT chloride 2. Analysis of this side-product by gas chromatography ion trap mass spectrometry (GC-MS), both in electron and chemical ionisation tandem MS modes, gave only degradation products. For example, 2 could not be detected but appeared to have rearranged to 3-(2-chloroethyl)indole 3 and 2-methyltetrahydro-beta-carboline 4, whereas HPLC analysis enabled the detection of 2. GC-MS is a standard tool for the fingerprinting of drug products. The identification of a particular synthetic route is based on the analysis of impurities, provided these side products can be established to be route-specific. The in situ detection of both 3 and 4 within a DMT sample may have led to erroneous conclusions with regards to the identification of the synthetic route.
[Predictors of medication non-adherence among a Moroccan sample of patients with schizophrenia: A cross sectional study].

PubMed

El Ammouri, A; Kisra, H

2017-12-01

Schizophrenia is a chronic, relapsing, mental disorder, and lack of adherence is a common and severe problem in such patients leadingto global and heavy consequences for patients (relapses, hospitalizations, impaired quality of life…), for the family and for society. Improved understanding of the underlying reasons will help to form intervention strategies relevant to the context. We aimed to assess medication adherence among stable patients suffering from schizophrenia and to identify factors associated with non-adherence. This is a retrospective cohort study of outpatients with schizophrenia at the psychiatric hospital Ar-razi of Salé (Maroc). The patients were aged over 18, clinically stabilized under the same treatment during the three months prior to inclusion. Data (demographic, clinical and therapeutic) was collected by a questionnaire developed for this purpose. Assessment of adherence and awareness of the disorder (insight) were performed respectively by two validated scales: Medication Adherence Rating Scale the (MARS) and scale Q8. Fourty percent of schizophrenic patients included in our study were not compliant to treatment. Compared to adherent patients, non-adherent patients had history of substance use (57.6 % vs. 42.4 %, P<0.05), were less aware of their disorder (77.8 % vs. 22.2 %, P<0.01), had significantly more drug intake per day (2.4 vs. 1.9, P<0.01), took significantly more tablets per day (2.8 vs. 2.2; P<0.05) and complained of significantly more side effects (43.2 vs. 56.8, P<0.05). A logistic regression model had shown that only side effects, lack of insight, and a history of substances use are significant predictors of poor adherence in patients with schizophrenia. The results of this work should guide our efforts to improve adherence in patients with schizophrenia. Waiting for new drugs with fewer side effects and better benefit/risk, some strategies would help to improve adherence to treatment. For example: implementation of strategies to manage psychoactive substance use, structured psycho-educational strategies to improve insight, and training therapists to improve the therapeutic alliance should be established. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.
In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease.

PubMed

Watt, Georgia; Karl, Tim

2017-01-01

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro . Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ 9 -tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa , show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone. The studies provide "proof of principle" that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described.
Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users

PubMed Central

Morgan, Celia JA; Noronha, Louise A; Muetzelfeldt, Mark; Fielding, Amanda

2013-01-01

There have been several recent efforts in the UK and the Netherlands to describe the harms of psychoactive substances based on ratings of either experts or drug users. This study aimed to assess the perceived benefits as well as harms of widely used recreational drugs, both licit and illicit, in an international sample of drug users. The survey was hosted at https://www.internationaldrugsurvey.org/ and was available in three languages. Residents reported their experience of 15 commonly used drugs or drug classes; regular users then rated their harms and benefits. In all, 5791 individuals from over 40 countries completed the survey, although the majority were from English speaking countries. Rankings of drugs differed across 10 categories of perceived benefits. Skunk and herbal cannabis were ranked consistently beneficial, whilst alcohol and tobacco fell below many classified drugs. There was no correlation at all between users’ harm ranking of drugs and their classification in schedules of the USA or ABC system in the UK. Prescription analgesics, alcohol and tobacco were ranked within the top 10 most harmful drugs. These findings suggest that neither the UK nor US classification systems act to inform users of the harms of psychoactive substances. It is hoped the results might inform health professionals and educators of what are considered to be both the harms and benefits of psychoactive substances to young people. PMID:23438502
Gender Orientation and Alcohol-Related Weight Control Behavior among Male and Female College Students

ERIC Educational Resources Information Center

Peralta, Robert L.; Barr, Peter B.

2017-01-01

Objective: We examine weight control behavior used to (a) compensate for caloric content of heavy alcohol use; and (b) enhance the psychoactive effects of alcohol among college students. We evaluate the role of gender orientation and sex. Participants: Participants completed an online survey (N = 651; 59.9% women; 40.1% men). Method: Weight…
Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats.

PubMed

Gatch, Michael B; Dolan, Sean B; Forster, Michael J

2017-04-01

Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds. The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexiophenone (α-PHP), α-pyrrolidinopentiothiophenone (α-PVT), 3,4-methylenedioxybutiophenone (MDPBP), and ethylone. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle. Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > α-PPP = α-PHP > ethylone > α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%. These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.
Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaushik, Gaurav, E-mail: kausgaur@isu.edu; Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA 95817; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817

Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic proteinmore » expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding {sup 2}H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post–conception days), and quantifying {sup 2}H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of {sup 2}H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical environmental concentrations is transmitted from mother to embryo. Our results, combined with previous evidence that carbamazepine may be associated with ASD in infants, warrant the closer examination of psychoactive pharmaceuticals in drinking water and their potential association with neurodevelopmental disorders.« less
Use Of Psychoactive Drugs Among Medical Undergraduates In Abbottabad.

PubMed

Nawaz, Haq; Khan, Aftab Alam; Bukhari, Saima

2017-01-01

Psychoactive substance abuse is prevalent among medical undergraduates of Pakistan, India & Western countries which can adversely affect the physical & psychological grooming of a medical undergraduate thus threatening to compromise their role as future physicians & health-care providers in the society. The objective of the present cross-sectional study was to explore the prevalence and patterns of psychoactive substance/drug consumption among undergraduate students of a public sector medical college in Abbottabad. Seven hundred and eighty participants after informed consent were requested to fill a questionnaire seeking information about their demographics, patterns & behaviours regarding ten common psychoactive substances of abuse including (Cigarettes, Benzodiazepines, naswar, cannabis, alcohol, amphetamine, opium, cocaine, heroin & organic solvents). Overall students who responded were 698 (89.48%). One hundred and fifty (21.49%) admitted to the use of a psychoactive substance in past or at present. Majority users (71.33%) were males. Overall (81.33%) users were living in hostel or a rented apartment. Substance abuse was more prevalent among senior students, i.e., 30.06% & 24.24% in 4th year & final year MBBS respectively. Majority of the consumers, i.e., 93 (62%) were falling in an age group between 15-20 years. Main reasons behind substance abuse were: psychological stress (49.33%) and pleasure seeking (42.67%). Substances/drugs used by students in order of preference were Cigarettes 115 (76.67%), Benzodiazepines 48 (32%), naswar 42 (28%), Cannabis 41 (27.33%), Alcohol 24 (16%), Amphetamine 22 (14.67%), Opium 15 (10%), Cocaine 14 (9.33%), Heroin 11 (7.33%) & Organic solvents 05 (3.33%). Use of more than one substance was observed in 70 (46.67%) students. It is concluded that prevalence of cigarette smoking, naswar, benzodiazepines, cannabis & alcohol is high among medical undergraduates in Abbottabad which is a matter of concern. Efforts are needed to create better awareness among them about the hazards of substance abuse on their health, upcoming professional career and ailing humanity under their care.
Legal high industry business and lobbying strategies under a legal market for new psychoactive substances (NPS, 'legal highs') in New Zealand.

PubMed

Rychert, Marta; Wilkins, Chris

2016-11-01

The establishment of a regulated legal market for new psychoactive substances (NPS, 'legal highs') under New Zealand's Psychoactive Substances Act (PSA) 2013 created a new commercial sector for psychoactive products, previously limited to alcohol and tobacco. To explore how the newly-recognised 'legal high' industry (LHI) viewed and responded to the changing regulatory and market environment. In-depth interviews with six key informants (KI) from the LHI: a leading entrepreneur, chemist, industry spokesperson, retailer, product buyer and a researcher commissioned by the LHI - were conducted, transcribed and analysed thematically. Formative work for the study included review of official LHI documents (websites, public submissions, self-regulation documents). The LHI stakeholders espoused an idealistic mission of shifting recreational users of alcohol, tobacco and illegal drugs towards "safer alternatives". Passage of the PSA was viewed as a success after years of lobbying led by pioneering LHI actors. The growth and professionalisation of the LHI resulted in an increasingly commercial market which challenged idealistic views of the original operators. LHI KI reported the targeting of young and low income customers, price cutting and increasing the strength of products as business strategies. Attempts by the LHI to self-regulate did not prevent escalation in the strength of products and fall in retail prices. The LHI reported outsourcing of manufacturing and exporting of their products to other countries, demonstrating an international business model. There was a tension between profit and idealistic motivations within the LHI and this increased as the sector became more commercialised. While the LHI distanced itself from both alcohol and tobacco, they reported the use of similar marketing, business and political lobbying strategies. Rules for engagement with new 'addictive consumption industries' are required to clarify the role they are permitted to play in the development of regulatory regimes for new psychoactive substances. Copyright © 2016 Elsevier B.V. All rights reserved.

Gaming under the influence: An exploratory study.

PubMed

Škařupová, Kateřina; Blinka, Lukas; Ťápal, Adam

2018-05-23

Background and aims Association between substance use and excessive play of online games exists both in theory and research. However, no study to date examined playing online games under the influence of licit and illicit drugs. Methods We questioned a convenient online sample of 3,952 Czech online gamers on their experiences and motives of using caffeine, alcohol, tobacco, psychoactive pharmaceuticals, and illicit drugs while playing massive multiplayer online games (MMOGs). Results The results showed low prevalence of illicit drug use while playing online games. Substance use was positively associated with intensity of gaming and both addiction and engagement; psychoactive substances with stimulating effect were linked to higher engagement and gaming intensity, whereas use of sedatives was associated with higher addiction score. Substance use varied slightly with the preference of game genre. Discussion Drug use while playing appears as behavior, which is mostly not related to gaming - it concerns mostly caffeine, tobacco, alcohol, or cannabis. For some users, however, drug use was fueled by motivations toward improving their cognitive enhancement and gaming performance.
Baclofen to prevent agitation in alcohol-addicted patients in the ICU: study protocol for a randomised controlled trial.

PubMed

Vourc'h, Mickael; Feuillet, Fanny; Mahe, Pierre-Joachim; Sebille, Véronique; Asehnoune, Karim

2016-08-19

Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30 % and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50 % of patients. This prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28 days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal (such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway (leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment. Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018. ClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016.
Marijuana and chocolate.

PubMed

James, J S

1996-10-18

Three substances in chocolate and cocoa powder may mimic cannabinoid by activating receptors or increasing anandamide levels. Anandamide is a lipid that binds to cannabinoid receptors and mimics the psychoactive effects of the drug. Chocolate is widely believed to enhance the effect of marijuana. A practical implication of this finding is that the amount of marijuana needed for medicinal purposes may be decreased by using it with chocolate, reducing both the risks and cost associated with marijuana.
Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer

DTIC Science & Technology

2013-02-01

looking at the interaction of the synthetic cannabinoid WIN55,212-2 and ionizing radiation has led to preliminary results implicating a novel site of...we found that the various cannabinoids do not interfere with the anti-proliferative effects of either treatment; furthermore, the synthetic ...aminoalkylindole series, is one of the most highly studied synthetic cannabinoids. It has been shown to produce the full spectrum of psychoactive effects
Cannabidiol--recent advances.

PubMed

Mechoulam, Raphael; Peters, Maximilian; Murillo-Rodriguez, Eric; Hanus, Lumír O

2007-08-01

The aim of this review is to present some of the recent publications on cannabidiol (CBD; 2), a major non-psychoactive constituent of Cannabis, and to give a general overview. Special emphasis is laid on biochemical and pharmacological advances, and on novel mechanisms recently put forward, to shed light on some of the pharmacological effects that can possibly be rationalized through these mechanisms. The plethora of positive pharmacological effects observed with CBD make this compound a highly attractive therapeutic entity.
Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

PubMed

Hysek, Cédric M; Simmler, Linda D; Schillinger, Nathalie; Meyer, Nicole; Schmid, Yasmin; Donzelli, Massimiliano; Grouzmann, Eric; Liechti, Matthias E

2014-03-01

Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).
'Legal highs'--novel and emerging psychoactive drugs: a chemical overview for the toxicologist.

PubMed

Gibbons, Simon

2012-01-01

'Legal highs' are psychoactive chemicals which are sold from 'head shops', the internet and from street suppliers and may be possessed without legal restriction. An increase in the marketing of these materials has resulted in a corresponding increase in published reports of their adverse effects. However, a lack of primary literature pertaining to their chemistry, pharmacology and toxicology, makes an evaluation of their harm difficult. This review covers the basic chemistry of these novel psychoactive compounds and relates them to endogenous neurotransmitters and existing drugs of abuse. A survey of the internet was used to identify websites that are marketing 'legal highs' in the UK. Trivial and systematic chemical compound names, for example methoxetamine, 4-methoxyphencycline, 4-fluorotropacocaine and ethyl phenidate were entered into PubMed to retrieve data on these compounds. This search elicited no citations. Other search terms which were more fruitful included desoxypipradrol, diphenylprolinol, methylenedioxy-2-amino-indane and methylenedioxy-2-amino-tetralin, alpha-methyltryptamine and 5-methoxy-N,N-diallyl-tryptamine. 'Legal highs' from the phenylethylamine, cocaine, tryptamine and phencyclidine classes are increasingly being marketed and, in the majority of cases, little is cited in the literature on their true chemical identity, pharmacology or toxicology. 'Legal highs' are gaining in popularity and present clear challenges to toxicologists and society as a whole. Whilst improved use of existing legislation and development of new legislation can be used to reduce the supply of these materials, investment in better education for young people on the harms associated with 'legal highs' is needed.
Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

PubMed

Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

2013-06-01

In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.
Dynamic vaccine blocks relapse to compulsive intake of heroin

PubMed Central

Schlosburg, Joel E.; Vendruscolo, Leandro F.; Bremer, Paul T.; Lockner, Jonathan W.; Wade, Carrie L.; Nunes, Ashlee A. K.; Stowe, G. Neil; Edwards, Scott; Janda, Kim D.; Koob, George F.

2013-01-01

Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. PMID:23650354
Psychoactive "bath salts" intoxication with methylenedioxypyrovalerone.

PubMed

Ross, Edward A; Reisfield, Gary M; Watson, Mary C; Chronister, Chris W; Goldberger, Bruce A

2012-09-01

Abuse of the psychoactive "designer drug" methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral toxicities. MDPV is the primary ingredient in so-called "bath salts," labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening. Copyright © 2012 Elsevier Inc. All rights reserved.
Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

PubMed Central

Hassan, Zurina; Bosch, Oliver G.; Singh, Darshan; Narayanan, Suresh; Kasinather, B. Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B.; Müller, Christian P.

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”), synthetic cannabinoids (e.g., “Spice”), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications. PMID:28868040
A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Maes, Hermine H; Sundquist, Kristina; Lichtenstein, Paul; Sundquist, Jan

2015-04-01

Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male-male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18-20% of the variance in liability, were non-specific. In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France.

PubMed

Orriols, Ludivine; Gaillard, Julia; Lapeyre-Mestre, Maryse; Roussin, Anne

2009-01-01

Drugs that can be obtained without a medical prescription in community pharmacies are used to treat minor pathologies that can easily be diagnosed by the patient. Some of these drugs contain psychoactive substances with a potential for abuse and dependence. However, there is a lack of data concerning their problematic use in a wide population. To explore the feasibility of a pharmacoepidemiological method to investigate misuse, non-medical use, abuse and dependence on drugs used for self-medication. This cross-sectional pilot study, conducted during a 2-month period (from 15 January to 15 March 2007), was based on the participation of community pharmacies in the Midi-Pyrénées region of France to collect patient data. Patients requesting one drug from a list of available drugs used for self-medication and containing psychoactive substances (codeine in analgesics, pseudoephedrine, dextromethorphan and histamine H(1) receptor antagonists [antihistamines]) were included in the study. A control group was set up that consisted of patients requesting antacid drugs. The pharmacy staff proposed to the patients that they filled in an anonymous questionnaire. The questionnaire was designed to investigate patterns of drug use and the harmful consequences of overuse (abuse). In addition, questions on lack of control over drug use were adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for evaluation of dependence. Thirty-two percent (n = 74) of the solicited pharmacies participated in the survey. Only 4.8% of the solicited patients (n = 817) refused to complete the questionnaire distributed by the pharmacy staff. The questionnaire was completed inside the pharmacy by 53.3% of the patients. The other patients took the questionnaire away from the pharmacy and 31.7% of them returned it in a prepaid envelope. The patient participation rate was 64.9%, and was higher for the psychoactive substance groups than the control group. Statistically significant differences on misuse (and/or non-medical use), abuse and dependence were obtained between the codeine and antacid groups. In the codeine group, among the patients having used the product in the previous month (n = 53), 15.1% misused the drug and/or used the drug for a non-medical reason, 7.5% were cases of abuse and 7.5% presented criteria of lack of control over drug use related to dependence on the substance for the psychoactive effects or for pain relief. The results obtained in this pilot study indicate that using anonymous self-administered questionnaires offered to patients by pharmacy staff is a reliable method to obtain information on the problematic use of drugs containing psychoactive substances purchased in a pharmacy for self-medication.
Mental health care for Brazilian juvenile offenders.

PubMed

Costa, Nilson do Rosário; Silva, Paulo Roberto Fagundes da

2017-05-01

This paper analyzes the use of psychoactive drugs by juvenile offenders in Brazil in socio-educational facilities (USEs). It describes the guidelines of the national public policy and the quality of mental healthcare coordination by subnational public governments. This work draws on the hypothesis that USEs vertical governance is associated with the use of psychoactive medication. This is comparative study of two cases in Rio Grande do Sul and Minas Gerais. Data resulted from a sample of medical records and interviews with key informants. The paper shows that vertical governance observed in Rio Grande do Sul is directly associated with high prevalence of mental health disorder diagnosis, use of psychoactive medication and psychiatric medicalization by juvenile offenders deprived of liberty. These findings indicate that sanctions of imprisonment for illegal acts are producing a set of medicalization decisions that undermine juveniles' health rights. The national mental health policy guidelines encourage cautious decisions. Psychotherapies and rehabilitation actions are the advocated first-line interventions. The poor management of the psychopharmacological intervention favors multiple prescriptions.
Novel psychoactive substances (NPS) use in severe mental illness (SMI) patients: Potential changes in the phenomenology of psychiatric diseases.

PubMed

Bersani, Giuseppe; Prevete, Elisabeth

2017-05-01

Literature is quite poor about the clinical effects of novel psychoactive substances (NPS) and the long-term consequences of NPS use in psychiatric patients. Consequently, it is of the greatest interest to examine which effects NPS can exert in patients with previous severe mental illness (SMI), such as psychotic patients. The aim of this work was a comprehensive review about NPS use in patients with SMI. We searched Medline or PubMed for relevant English-language citations and reviews describing relationships between NPS use and mental disorders, as well as for the main groups of substances and associated psychiatric manifestations. All studies reporting single case or case series of patients were selected. The NPS use in patients with SMI is probably underestimated. The one existing systematic review considers only 14 studies, 12 of which are case reports. Most clinical results report acute symptom exacerbation of preexisting psychosis. Paranoid, mood, and aggression symptoms occur more frequently. NPS use could modify clinical features of SMI, but these conclusions cannot be generalizable. More evidence is needed to establish the causal and effective connection between NPS use and course of illness, type of psychiatric symptoms, and outcome of treatment in terms of adherence or response. Copyright © 2017 John Wiley & Sons, Ltd.
Delta-9-Tetrahydrocannabinol Potentiates Fear Memory Salience Through Functional Modulation of Mesolimbic Dopaminergic Activity States.

PubMed

Fitoussi, Aurelie; Zunder, Jordan; Tan, Huibing; Laviolette, Steven R

2018-05-18

Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NAc (NASh) and examined how THC may modulate the processing of fear-related emotional memory and concomitant activity states of the mesolimbic DA system. We report that intra-NASh THC dose-dependently potentiates the emotional salience of normally sub-threshold fear-conditioning cues. These effects were dependent upon intra-VTA transmission through GABAergic receptor mechanisms and intra-NASh DAergic transmission. Furthermore, doses of intra-NASh THC that potentiated fear memory salience were found to modulate intra-VTA neuronal network activity by increasing the spontaneous firing and bursting frequency of DAergic neurons whilst decreasing the activity levels of a subpopulation of putative GABAergic VTA neurons. These findings demonstrate that THC can act directly in the NASh to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DAergic transmission. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes.

PubMed

Manzanares, J; Julian, Md; Carrascosa, A

2006-07-01

Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB(1)mediated suppression of mast cell activation responses, CB(2)-mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain.
Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2014-09-01

46 NEY-1413 FINAL Version 10.30 JANUARY 2014 ABBREVIATIONS AE Adverse Event AASM American Academy of Sleep Medicine BzRAs Benzodiazepine...ketoconazole, prescription or over- the-counter medications or herbal supplements containing psychoactive properties or stimulants in the judgment of the...medical conditions; 12.) Current use of statins, ketoconazole, prescription or over-the-counter medications or herbal supplements containing
Exploring the Attractiveness of New Psychoactive Substances (NPS) among Experienced Drug Users.

PubMed

van Amsterdam, Jan G C; Nabben, Ton; Keiman, Daan; Haanschoten, Gijs; Korf, Dirk

2015-01-01

A growing number of New Psychoactive Substances (NPS) appear yearly on the European market (81 for the first time in 2013, adding to a total of over 350 NPS). Using semi-structured interviews with 25 Dutch experienced recreational drug users, the role of the Internet and friends in gathering and exchanging information about NPS was elaborated. Furthermore, we investigated how NPS were acquired and which aspects make NPS more or less attractive, including their legal status. It appeared that the Internet was an important source of information about NPS in general. Personal experiences with NPS were preferably shared face-to-face with friends, as for privacy reasons users were cautious to post their experiences on web sites and forums. NPS were usually obtained or bought from friends or-to a lesser extent-purchased via the Internet. The preference for a specific NPS depended on the desired effects (mostly stimulant or psychedelic), price (similar to MDMA or amphetamine), duration of effect (preferably around four hours), and setting (at home, at festivals, or in nightlife). Legal status was not relevant for the decision to use NPS. Most NPS are not superior to the already marketed drugs, and do not displace conventional illicit drugs.
Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine.

PubMed

Robson, Philip

2011-09-01

There is a growing consensus that cannabis dependence is a substantial and underappreciated problem. The key component responsible for the euphoric effects of cannabis and its dependence potential is δ-9-tetrahydrocannabinol (THC). THC-containing cannabinoid medicines theoretically pose a risk of abuse and dependence. In order to evaluate the potential of Sativex to cause cannabis-like psychoactivity, abuse or dependence relevant data from all published papers have been reviewed along with the integrated safety analysis for Sativex use in multiple sclerosis (MS) patients on file at GW Pharmaceuticals. In clinical trials, intoxication scores have been low and euphoria reported by only 2.2% of patients. Tolerance has not occurred, abrupt withdrawal has not resulted in a formal withdrawal syndrome, and no cases of abuse or diversion have been reported to date. A formal abuse liability study of Sativex in experienced cannabis smokers showed some abuse potential in comparison with placebo at higher doses, but scores were consistently lower than equivalent doses of THC. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

PubMed

Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

2016-08-01

Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.
Artificial neural networks and the study of the psychoactivity of cannabinoid compounds.

PubMed

Honório, Káthia M; de Lima, Emmanuela F; Quiles, Marcos G; Romero, Roseli A F; Molfetta, Fábio A; da Silva, Albérico B F

2010-06-01

Cannabinoid compounds have widely been employed because of its medicinal and psychotropic properties. These compounds are isolated from Cannabis sativa (or marijuana) and are used in several medical treatments, such as glaucoma, nausea associated to chemotherapy, pain and many other situations. More recently, its use as appetite stimulant has been indicated in patients with cachexia or AIDS. In this work, the influence of several molecular descriptors on the psychoactivity of 50 cannabinoid compounds is analyzed aiming one obtain a model able to predict the psychoactivity of new cannabinoids. For this purpose, initially, the selection of descriptors was carried out using the Fisher's weight, the correlation matrix among the calculated variables and principal component analysis. From these analyses, the following descriptors have been considered more relevant: E(LUMO) (energy of the lowest unoccupied molecular orbital), Log P (logarithm of the partition coefficient), VC4 (volume of the substituent at the C4 position) and LP1 (Lovasz-Pelikan index, a molecular branching index). To follow, two neural network models were used to construct a more adequate model for classifying new cannabinoid compounds. The first model employed was multi-layer perceptrons, with algorithm back-propagation, and the second model used was the Kohonen network. The results obtained from both networks were compared and showed that both techniques presented a high percentage of correctness to discriminate psychoactive and psychoinactive compounds. However, the Kohonen network was superior to multi-layer perceptrons.
Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations.

PubMed

Kaushik, Gaurav; Xia, Yu; Pfau, Jean C; Thomas, Michael A

2017-11-20

Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10μM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development. Copyright © 2017 Elsevier B.V. All rights reserved.
Effects of Cannabinoids on T-cell Function and Resistance to Infection

PubMed Central

Eisenstein, Toby K.

2015-01-01

This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of Δ9-THC extracted from the marijuana plant, and synthetic cannabinoids. Of particular interest are synthetic compounds that are CB2 receptor (CB2R) selective agonists. As the CB2R is principally expressed on cells of the immune system, agonists that target this receptor, and not CB1 (which is mainly expressed on neurons), have the possibility of altering immune function without psychoactive effects. The overall conclusion of the studies discussed in this review is that cannabinoids that bind to the CB2 receptor, including Δ9-THC and CB2 selective agonists are immunosuppressive. The studies provide objective evidence for potentially beneficial effects of marijuana and Δ9-THC on the immune system in conditions where it is desirable to dampen immune responses. Evidence is also reviewed supporting the conclusion that these same compounds can sensitize to some infections through their immunosuppressive activities, but not to others. An emerging area of investigation that is reviewed is evidence to support the conclusion that CB2 selective agonists are a new class of immunosuppressive and anti-inflammatory compounds that may have exceptional beneficial effects in a variety of conditions, such as autoimmune diseases and graft rejection, where it is desirable to dampen the immune response without psychoactive effects. PMID:25876735
Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

PubMed

Kendler, Kenneth S; Myers, John; Prescott, Carol A

2007-11-01

Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence appear to be specific to those substances.
In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease

PubMed Central

Watt, Georgia; Karl, Tim

2017-01-01

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone. The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described. PMID:28217094
"Wild cannabis": A review of the traditional use and phytochemistry of Leonotis leonurus.

PubMed

Nsuala, Baudry N; Enslin, Gill; Viljoen, Alvaro

2015-11-04

Leonotis leonurus, locally commonly known as "wilde dagga" (=wild cannabis), is traditionally used as a decoction, both topically and orally, in the treatment of a wide variety of conditions such as haemorrhoids, eczema, skin rashes, boils, itching, muscular cramps, headache, epilepsy, chest infections, constipation, spider and snake bites. The dried leaves and flowers are also smoked to relieve epilepsy. The leaves and flowers are reported to produce a mild euphoric effect when smoked and have been said to have a similar, although less potent, psychoactive effect to cannabis. To amalgamate the botanical aspects, ethnopharmacology, phytochemistry, biological activity, toxicity and commercial aspects of the scientific literature available on L. leonurus. An extensive review of the literature from 1900 to 2015 was carried out. Electronic databases including Scopus, SciFinder, Pubmed, Google Scholar and Google were used as data sources. All abstracts, full-text articles and books written in English were considered. The phytochemistry of particularly the non-volatile constituents of L. leonurus has been comprehensively investigated due to interest generated as a result of the wide variety of biological effects reported for this plant. More than 50 compounds have been isolated and characterised. L. leonurus contains mainly terpenoids, particularly labdane diterpenes, the major diterpene reported is marrubiin. Various other compounds have been reported by some authors to have been isolated from the plant, including, in the popular literature only, the mildly psychoactive alkaloid, leonurine. Leonurine has however, never been reported by any scientific analysis of the extracts of L. leonurus. Despite the publication of various papers on L. leonurus, there is still, however, the need for definitive research and clarification of other compounds, including alkaloids and essential oils from L. leonurus, as well as from other plant parts, such as the roots which are extensively used in traditional medicine. The traditional use by smoking also requires further investigation as to how the chemistry and activity are affected by this form of administration. Research has proven the psychoactive effects of the crude extract of L. leonurus, but confirmation of the presence of psychoactive compounds, as well as isolation and characterization, is still required. Deliberate adulteration of L. leonurus with synthetic cannabinoids has been reported recently, in an attempt to facilitate the marketing of these illegal substances, highlighting the necessity for refinement of appropriate quality control processes to ensure safety and quality. Much work is therefore still required on the aspect of quality control to ensure safety, quality and efficacy of the product supplied to patients, as this plant is widely used in South Africa as a traditional medicine. Commercially available plant sources provide a viable option for phytochemical research, particularly with regard to the appropriate validation of the plant material (taxonomy) in order to identify and delimit closely related species such as L. leonurus and L. nepetifolia which are very similar in habit. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens.

PubMed

Ovadia, H; Wohlman, A; Mechoulam, R; Weidenfeld, J

1995-02-01

In the present study we have characterized the hypothermic effect of the psychoactive cannabinoid HU-210, by investigating its interaction with the endogenous pyrogens, IL-1 and PGE2. We also studied the involvement of the adrenergic system in mediation of this hypothermic effect. Injection of HU-210 directly into the preoptic area caused a dose dependent reduction of rectal temperature from 37 to 32.1 degrees C. Injection of the non-psychoactive analog, HU-211 which does not bind to brain cannabinoid receptor, did not affect body temperature. Injection of the adrenergic agonists, CGP-12177 and clonidine (beta, and alpha adrenergic agonists, respectively) abrogated the hypothermia induced by HU-210. Injection of the adrenergic antagonists, prazosin (alpha 1) and propranolol (beta) enhanced the hypothermic effect of HU-210. Intracerebral administration of IL-1 or PGE2 to rats pretreated with HU-210 caused a transient inhibition of the hypothermia. The ex vivo rate of basal or bacterial endotoxin-induced synthesis of PGE2 by different brain regions, including the preoptic area was not affected by HU-210 administration. These results suggest that the synthetic cannabinoid HU-210 acts in the preoptic area, probably via the brain cannabinoid receptor to induce hypothermia. The hypothermic effect can be antagonized by adrenergic agonists and enhanced by adrenergic antagonists. HU-210 does not interfere with the pyrogenic effect of IL-1 or PGE2.
The Endocannabinoid System as a Target for Treatment of Breast Cancer

DTIC Science & Technology

2009-08-01

4 Introduction ∆9-tetradyrocannabinol (THC), the chief psychoactive constituent of marijuana , as well as other naturally occurring and... synthetically derived cannabinoids possess potential therapeutic effects related to cancer treatment, including reduction in nausea and vomiting...However, there is little enthusiasm for the development of mixed CB1/CB2 receptor agonists for therapeutic uses because of their marijuana -like and
Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2013-12-18

9.28MARCH2013 AE Adverse Event AASM American Academv of Sleep Medicine BzRAs B enzo diazepine Receptor A goni sts CRC Clinical Research Center CCRC University...medical conditions; 12.) Current use of statins, ketoconazole, prescription or over- the-counter medications or herbal supplements containing...medications or herbal supplements containing psychoactive properties or stimulants in the judgment of the Investigator-Sponsor or Medical Monitor; 13
Heritability of lifetime ecstasy use.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vreeker, Annabel; Brunt, Tibor M; Willemsen, Gonneke; Boomsma, Dorret I; Vink, Jacqueline M

2017-09-01

Ecstasy is a widely used psychoactive drug that users often take because they experience positive effects such as increased euphoria, sociability, elevated mood, and heightened sensations. Ecstasy use is not harmless and several immediate and long term side effects have been identified. Lifetime ecstasy use is likely to be partly influenced by genetic factors, but no twin study has determined the heritability. Here, we apply a classical twin design to a large sample of twins and siblings to estimate the heritability of lifetime ecstasy use. The sample comprised 8500 twins and siblings aged between 18 and 45 years from 5402 families registered at the Netherlands Twin Registry. In 2013-2014 participants filled out a questionnaire including a question whether they had ever used ecstasy. We used the classical twin design to partition the individual differences in liability to ecstasy use into that due to genetic, shared environmental, and residual components. Overall, 10.4% of the sample had used ecstasy during their lifetime, with a somewhat higher prevalence in males than females. Twin modelling indicated that individual differences in liability to lifetime ecstasy use are for 74% due to genetic differences between individuals, whereas shared environmental and residual factors explain a small proportion of its liability (5% and 21%, respectively). Although heritability estimates appeared to be higher for females than males, this difference was not significant. Lifetime ecstasy use is a highly heritable trait, which indicates that some people are genetically more vulnerable to start using ecstasy than others. Copyright © 2017. Published by Elsevier B.V.
Traditional medicine applied by the Saraguro yachakkuna: a preliminary approach to the use of sacred and psychoactive plant species in the southern region of Ecuador

PubMed Central

2014-01-01

Background During the colonial period, the indigenous saraguros maintained their traditions, knowledge, and practices to restore and preserve the health of their members. Unfortunately, many of their practices and medicinal resources have not been documented. In this study, we sought to document the traditional healers’ (yachakkuna saraguros) knowledge about medicinal and psychoactive plants used in the mesas and in magical-religious rituals. The study was conducted under a technical and scientific cooperation agreement between the Universidad Técnica Particular de Loja (UTPL), the Dirección Provincial de Salud de Loja (DPSL), and the Saraguro Healers Council (Consejo de Sanadores de Saraguro). Methods For the present study, the DPSL and Saraguro Healers Council selected the 10 yachakkuna most recognized for their knowledge and their use of sacred and psychoactive species. Ten interviews with the selected yachakkuna were conducted between 2010 and 2011 to ascertain how the Saraguro traditional healing system is structured and to obtain a record of the sacred and medicinal plant species used to treat supernatural diseases and for psychoactive purposes. Results The present study describes the traditional health system in the Saraguro indigenous community located in southern Ecuador. It also describes the main empirical methods used to diagnose diseases: direct physical examination of the patient, observation of the patient’s urine, documentation of the patient’s pulse, limpia, palpation and visionary methods, including supernatural diseases (susto, vaho de agua, mal aire, mal hecho, shuka) and reports of the use of sacred and medicinal psychoactive plants, such as the San Pedro cactus (Echinopsis pachanoi), wandug (Brugmansia spp.), and tobacco (Nicotiana spp.). This study also describes the rituals (limpia, soplada) employed by the Saraguro yachakkuna to treat supernatural diseases. Finally, we report on the main plants used during limpia in the Saraguro community. Conclusion The current traditional health system in the Saraguro community is the cultural expression of the Saraguros’ presence as an Andean group in southern Ecuador: it represents their character as indigenous group, their ability to survive as a community despite strong external pressure, and the desire to maintain their ancient healing heritage. PMID:24565054
Traditional medicine applied by the Saraguro yachakkuna: a preliminary approach to the use of sacred and psychoactive plant species in the southern region of Ecuador.

PubMed

Armijos, Chabaco; Cota, Iuliana; González, Silvia

2014-02-24

During the colonial period, the indigenous saraguros maintained their traditions, knowledge, and practices to restore and preserve the health of their members. Unfortunately, many of their practices and medicinal resources have not been documented. In this study, we sought to document the traditional healers' (yachakkuna saraguros) knowledge about medicinal and psychoactive plants used in the mesas and in magical-religious rituals. The study was conducted under a technical and scientific cooperation agreement between the Universidad Técnica Particular de Loja (UTPL), the Dirección Provincial de Salud de Loja (DPSL), and the Saraguro Healers Council (Consejo de Sanadores de Saraguro). For the present study, the DPSL and Saraguro Healers Council selected the 10 yachakkuna most recognized for their knowledge and their use of sacred and psychoactive species. Ten interviews with the selected yachakkuna were conducted between 2010 and 2011 to ascertain how the Saraguro traditional healing system is structured and to obtain a record of the sacred and medicinal plant species used to treat supernatural diseases and for psychoactive purposes. The present study describes the traditional health system in the Saraguro indigenous community located in southern Ecuador. It also describes the main empirical methods used to diagnose diseases: direct physical examination of the patient, observation of the patient's urine, documentation of the patient's pulse, limpia, palpation and visionary methods, including supernatural diseases (susto, vaho de agua, mal aire, mal hecho, shuka) and reports of the use of sacred and medicinal psychoactive plants, such as the San Pedro cactus (Echinopsis pachanoi), wandug (Brugmansia spp.), and tobacco (Nicotiana spp.). This study also describes the rituals (limpia, soplada) employed by the Saraguro yachakkuna to treat supernatural diseases. Finally, we report on the main plants used during limpia in the Saraguro community. The current traditional health system in the Saraguro community is the cultural expression of the Saraguros' presence as an Andean group in southern Ecuador: it represents their character as indigenous group, their ability to survive as a community despite strong external pressure, and the desire to maintain their ancient healing heritage.
Experimentation with psychoactive substances by public school students

PubMed Central

de Andrade, Maria Eliane; Santos, Igor Henrique Farias; de Souza, Antônio Araújo Menezes; Silva, Aliane Caroline Santos; Leite, Tatiane dos Santos; Oliveira, Cristiane Costa da Cunha; de Albuquerque, Ricardo Luiz Cavalcanti

2017-01-01

ABSTRACT OBJECTIVE To analyze the prevalence of exposure to psychoactive substances in public students of basic education and its association with sociodemographic characteristics. METHODS This is a cross-sectional survey conducted from March to September 2015, involving 1,009 students of the basic and high school education in 20 public schools in the municipality of Aracaju, State of Sergipe, Brazil. The data have been compiled using questionnaires previously applied in national studies of the Brazilian Center for Psychotropic Drugs. The variables have been dichotomized for later logistic regression using the Chi-square test to analyze associations between experimentation with psychoactive substances and other sociodemographic variables; odds ratio and confidence intervals have also been calculated. The level of significance adopted was 5%. RESULTS We have identified that 69.6% of the students have experimented alcohol and 12.4% cigarettes. Age (≥ 15 years) has shown a significant association with experimentation with alcohol (p < 0.001) and cigarettes (p = 0.02), acting as risk factor in both cases (OR = 2.34 and 1, 78, respectively), but it acted as a protective factor for the use of inhalants (p = 0.03 and OR = 0.58) and weight loss medication (p = 0.006 and OR = 0.44). Religious practice had a significant association with experimentation with alcohol (p = 0.01), functioning as a protective factor (OR = 0.56). CONCLUSIONS We have concluded that the psychoactive substance most experienced by students was alcohol, followed by cigarettes, and chance for experimentation increases after the age of 15. Religious practice, in turn, acts as a protective factor for experimentation with alcohol. PMID:28876413
Categorization of psychoactive substances into "hard drugs" and "soft drugs": a critical review of terminology used in current scientific literature.

PubMed

Janik, Peter; Kosticova, Michaela; Pecenak, Jan; Turcek, Michal

2017-11-01

Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.
Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC-MS, LC-MSn, and LC-HR-MS-MS.

PubMed

Michely, Julian A; Helfer, Andreas G; Brandt, Simon D; Meyer, Markus R; Maurer, Hans H

2015-10-01

N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamine derivatives commonly referred to as so-called new psychoactive substances (NPS). They have psychoactive effects that may be similar to those of other tryptamine derivatives. The objectives of this work were to study the metabolic fate and detectability, in urine, of DALT and 5-MeO-DALT. For metabolism studies, rat urine obtained after high-dose administration was prepared by precipitation and analyzed by liquid chromatography-high-resolution mass spectrometry (LC-HR-MS-MS). On the basis of the metabolites identified, several aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations thereof are proposed as the main metabolic pathways for both compounds. O-Demethylation of 5-MeO-DALT was also observed, in addition to extensive glucuronidation or sulfation of both compounds after phase I transformation. The cytochrome P450 (CYP) isoenzymes predominantly involved in DALT metabolism were CYP2C19, CYP2D6, and CYP3A4; those mainly involved in 5-MeO-DALT metabolism were CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detectability studies, rat urine was screened by GC-MS, LC-MS(n), and LC-HR-MS-MS after administration of low doses. LC-MS(n) and LC-HR-MS-MS were deemed suitable for monitoring consumption of both compounds. The most abundant targets were a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC-MS enabled screening of DALT by use of its main metabolites only.
Toxicology and methods of committing suicide other than overdose.

PubMed

Coklo, Miran; Stemberga, Valter; Cuculic, Drazen; Sosa, Ivan; Bosnar, Alan

2009-11-01

Suicide represents a serious public health problem throughout the world. Toxicology plays a crucial role in the investigation of suicide. Psychoactive substances are recognized in the literature as the main suicide-generating stimuli. Ethanol is known to produce disinhibition and increased self-confidence. Other psychoactive substances can predominantly be central nervous system (CNS) stimulants or depressors. In cases of overdose as a method of suicide, the link between toxicology and the method of suicide is a matter of common sense and requires no additional explanation. On the other hand, in cases of non-overdose suicides this link is much more complex, and has not yet been extensively elucidated. We hypothesize a close relationship between toxicology and the choice of the method of committing suicide other than overdose. Negative findings may reflect either poor prescribed drug compliance in psychiatric patients, or suggest the role of other (non-toxicological) suicide-generating stimuli. On the other hand, positive findings influence the choice of the suicide method in a way that it depends on the prevalence of either stimulation or depression of the CNS, and consequent degree of behavioral aggression. Simplified, if the prevailing effect is CNS stimulation (with an increase in aggression), the method would be more drastic and more immediately fatal one, while with the CNS depression the method would be less immediately fatal and less drastic. There are only a few studies on the prevalence of psychoactive substances amongst completed suicides and even fewer studies have attempted to examine the relationship between substances used and the circumstances surrounding suicide. In evaluation of our hypothesis, we suggest thorough studies of toxicology and the choice of methods of committing suicides other than overdose. The scientific knowledge gained this way will eventually make toxicology a useful target in suicide prevention, especially amongst younger population.
Promoting innovation and excellence to face the rapid diffusion of novel psychoactive substances in the EU: the outcomes of the ReDNet project.

PubMed

Corazza, Ornella; Assi, Sulaf; Simonato, Pierluigi; Corkery, John; Bersani, Francesco Saverio; Demetrovics, Zsolt; Stair, Jacqueline; Fergus, Suzanne; Pezzolesi, Cinzia; Pasinetti, Manuela; Deluca, Paolo; Drummond, Colin; Davey, Zoe; Blaszko, Ursula; Moskalewicz, Jacek; Mervo, Barbara; Furia, Lucia Di; Farre, Maggi; Flesland, Liv; Pisarska, Agnieszka; Shapiro, Harry; Siemann, Holger; Skutle, Arvid; Sferrazza, Elias; Torrens, Marta; Sambola, F; van der Kreeft, Peer; Scherbaum, Norbert; Schifano, Fabrizio

2013-07-01

The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools. Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in eight languages from collaborating countries. These included the following: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning environments (Second Life). The Recreational Drugs European Network project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel information and communication technology-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both European Union/international agencies and national policy makers. Web-monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge. Copyright © 2013 John Wiley & Sons, Ltd.
The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports.

PubMed

Sanz, Camila; Tagliazucchi, Enzo

2018-01-01

Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology ("what it feels like" to experience these states) is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD), whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception ("see," "visual," "face," "reality," "color"), emotion ("fear"), setting ("outside," "inside," "street," "front," "behind") and relatives ("mom," "dad," "brother," "parent," "family") were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain physiology.
[Common mental disorders and the use of psychoactive drugs: the impact of socioeconomic conditions].

PubMed

Lima, Maria Cristina Pereira; Menezes, Paulo Rossi; Carandina, Luana; Cesar, Chester Luiz Galvão; Barros, Marilisa Berti de Azevedo; Goldbaum, Moisés

2008-08-01

To evaluate the influence of socioeconomic conditions on the association between common mental disorders and the use of health services and psychoactive drugs. This was a population-based cross-sectional study conducted in the city of Botucatu, Southeastern Brazil. The sample was probabilistic, stratified and cluster-based. Interviews with 1,023 subjects aged 15 years or over were held in their homes between 2001 and 2002. Common mental disorders were evaluated using the Self-Reporting Questionnaire (SRQ-20). The use of services was investigated in relation to the fortnight preceding the interview and the use of psychotropic drugs, over the preceding three days. Logistic regression was used for multivariable analysis, and the design effect was taken into consideration. Out of the whole sample, 13.4% (95% CI: 10.7;16.0) had sought health services over the fortnight preceding the interview. Seeking health services was associated with female gender (OR=2.0) and the presence of common mental disorders (OR=2.2). 13.3% of the sample (95% CI: 9.2;17.5) said they had used at least one psychotropic drug, especially antidepressives (5.0%) and benzodiazepines (3.1%). In the multivariable analysis, female gender and the presence of common mental disorders remained associated with the use of benzodiazepines. Per capita income presented a direct and independent association with the use of psychoactive drugs: the greater the income, the greater the use of these drugs was. Lower income was associated with the presence of common mental disorders, but not with the use of psychotropic drugs. The association of common mental disorders and the use of psychotropic drugs in relation to higher income strengthens the hypothesis that inequality of access to medical services exists among this population.

[The usage of psychoactive substances among secondary school students in Nowy Sacz].

PubMed

Ogonowska, Dorota; Pach, Dorota; Targosz, Dorota

2009-01-01

The results of anonymous questionnaire research on psychoactive substances in two last classes of high school pupils in Nowy Sacz are presented in the study. Only 1.7% of the examined students do not perceive the psychoactive substances as a real problem existing at school, 9.6% have no opinion. The rest (88.7%) perceive it as an already existing problem, where 36% as a very serious one. Alcohol, cigarette smoking, marijuana, hashish or crack and medical drugs are the most common substances, being used mostly for fun and relaxation. Pupils opinions were evaluated on addictive properties of the substances. The essential difference between those who initiated drugs vs. those who did not has was also evaluated. Tobacco, cocaine, heroine and crack have been considered the most addictive. Health consequences followed by moral and ethical principles are the main rules against taking drugs. Only 4.1% of examined individuals question the fact that schools should take involvement in whether students take drugs the rest expect some punishment for a school drug dealers and prophylaxis (proposal of interesting work-shops, lectures).
[1-benzylpiperazine (BZP) and 1-(3-trifluorométhylphényl)pipérazine (TFMPP): emergence of two agents which lead to misuse].

PubMed

Lecompte, Y; Roussel, O; Perrin, M

2008-03-01

1-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are psychoactive agents which have become available on the illicit drug market in France since 2006. These compounds are employed for their stimulating, enacting, and "recreational" properties. The combination of BZP and TFMPP enables drug users to reproduce the domaminergic and serotoninergic components of amphetamine derivatives. Intoxication can be life threatening for BZP. This compound has been detected, in association with other psychoactive agents with similar action, in several fatal cases. In addition, there is a potential risk of addiction, confirmed in animal models. The toxicity of TFMPP appears to be weaker with no apparent risk of addiction. There is however a risk of serious psychiatric manifestations and serotoninergic syndrome. There are certain national regulations, but to date no international regulations have been developed for BZP and TFMPP. In the European Union, BZP is now being monitored in compliance with the 10 May 2005 decision of the Commision on information sharing, risk evaluation, and control relative to new psychoactive agents.
Medicating the mind: a Kantian analysis of overprescribing psychoactive drugs

PubMed Central

Manninen, B A

2006-01-01

Psychoactive drugs are being prescribed to millions of Americans at an increasing rate. In many cases these drugs are necessary in order to overcome debilitating emotional problems. Yet in other instances, these drugs are used to supplant, not supplement, interpersonal therapy. The process of overcoming emotional obstacles by introspection and the attainment of self knowledge is gradually being eroded via the gratuitous use of psychoactive medication in order to rapidly attain a release from the common problems that life inevitably presents us with. In this paper, I argue that Kant's formula of humanity, which maintains that persons ought never to treat others or themselves soley as a means to an end, proscribes this. Moreover, Kant argues that we have an imperfect duty of self development, and I argue that we fail to adhere to such a duty whenever we seek to evade the process of introspection and self knowledge in favour of the expedient results that drugs may provide us with as we attempt to overcome the emotional hurdles in our lives. PMID:16446415
Hunting and hallucinogens: The use psychoactive and other plants to improve the hunting ability of dogs.

PubMed

Bennett, Bradley C; Alarcón, Rocío

2015-08-02

Cultures throughout the world give plants to their dogs in order to improve hunting success. These practices are best developed in lowland Ecuador and Peru. There is no experimental evidence for the efficacy of these practices nor critical reviews that consider possible pharmacological effects on dogs based on the chemistry of the ethnoverterinary plants. This review has three specific aims: (1) determine what plants the Ecuadorian Shuar and Quichua give to dogs to improve their hunting abilities, (2) determine what plants other cultures give to dogs for the same purpose, and (3) assess the possible pharmacological basis for the use of these plants, particularly the psychoactive ones. We gathered Shuar (Province of Morona-Santiago) and Quichua (Napo and Orellano Provinces) data from our previous publications and field notes. All specimens were vouchered and deposited in QCNE with duplicates sent to NY and MO. Data presented from other cultures derived from published studies on ethnoveterinary medicine. Species names were updated, when necessary, and family assignments follow APG III (Angiosperm Phylogeny Group, 2009. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG III. Bot. J. Linn. Soc. 161, 105-121). Chemical data were found using PubMed and SciFinder. The Shuar and Quichua of Ecuador use at least 22 species for ethnoveterinary purposes, including all but one of their principal hallucinogens. Literature surveys identified 43 species used in other cultures to improve hunting ability. No published studies have examined the pharmacological active of these plant species in dogs. We, thus, combined phytochemical data with the ethnobotanical reports of each plant and then classified each species into a likely pharmacological category: depuratives/deodorant, olfactory sensitizer, ophthalmic, or psychoactive. The use of psychoactive substances to improve a dog׳s hunting ability seems counterintuitive, yet its prevalence suggests that it is both adaptive and that it has an underlying pharmacological explanation. We hypothesize that hallucinogenic plants alter perception in hunting dogs by diminishing extraneous signals and by enhancing sensory perception (most likely olfaction) that is directly involved in the detection and capture of game. If this is true, plant substances also might enhance the ability of dogs to detect explosives, drugs, human remains, or other targets for which they are valued. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
The endogenous cannabinoid anandamide shares discriminative stimulus effects with ∆(9)-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice.

PubMed

Walentiny, D Matthew; Gamage, Thomas F; Warner, Jonathan A; Nguyen, Thanh K; Grainger, Darren B; Wiley, Jenny L; Vann, Robert E

2011-04-10

The endogenous cannabinoid system has been noted for its therapeutic potential, as well as the psychoactivity of cannabinoids such as Δ9-tetrahydrocannabinol (THC). However, less is known about the psychoactivity of anandamide (AEA), an endocannabinoid ligand. Thus, the goals of this study were to establish AEA as a discriminative stimulus in transgenic mice lacking fatty acid amide hydrolase (i.e., FAAH -/- mice unable to rapidly metabolize AEA), evaluate whether THC or oleamide, a fatty acid amide, produced AEA-like responding, and assess for CB(1) mediation of AEA's discriminative stimulus. Mice readily discriminated between 6mg/kg AEA and vehicle in a two-lever drug discrimination task. AEA dose-dependently generalized to itself. THC elicited full AEA-like responding, whereas oleamide failed to substitute. The CB(1) antagonist rimonabant attenuated AEA- and THC-induced AEA-appropriate responding, demonstrating CB(1) mediation of AEA's discriminative stimulus. These findings suggest that, in the absence of FAAH, AEA produces intoxication comparable to THC, and consequently to marijuana. Copyright © 2011 Elsevier B.V. All rights reserved.
Simultaneous LC-MS/MS determination of 40 legal and illegal psychoactive drugs in breast and bovine milk.

PubMed

López-García, Ester; Mastroianni, Nicola; Postigo, Cristina; Valcárcel, Yolanda; González-Alonso, Silvia; Barceló, Damia; López de Alda, Miren

2018-04-15

This work presents a fast, sensitive and reliable multi-residue methodology based on fat and protein precipitation and liquid chromatography-tandem mass spectrometry for the determination of common legal and illegal psychoactive drugs, and major metabolites, in breast milk. One-fourth of the 40 target analytes is investigated for the first time in this biological matrix. The method was validated in breast milk and also in various types of bovine milk, as tranquilizers are occasionally administered to food-producing animals. Absolute recoveries were satisfactory for 75% of the target analytes. The use of isotopically labeled compounds assisted in correcting analyte losses due to ionization suppression matrix effects (higher in whole milk than in the other investigated milk matrices) and ensured the reliability of the results. Average method limits of quantification ranged between 0.4 and 6.8 ng/mL. Application of the developed method showed the presence of caffeine in breast milk samples (12-179 ng/mL). Copyright © 2017 Elsevier Ltd. All rights reserved.
Psychoactive substances of the South Seas: betel, kava and pituri.

PubMed

Cawte, J

1985-03-01

Before white man brought his alcohol to the South Pacific, the indigenes were using many wild plants possessing psychoactive properties. The most prominent were betel in much of Melanesia, kava in much of Polynesia, and pituri in much of Australia. The use of each of these three drugs was widespread, institutionalised as a ritual and the occasion for extensive trade. Each was valued for its effect in reducing tension or in producing altered states of consciousness. Each was also capable of inducing intoxication. Since few physicians nowadays have had my opportunity to observe the use of all three of these substances, their main features are recalled here. Attention is paid to their traditional use and probable future use, to their pharmacological and clinical properties, and to their place in the zeitgeist of people and period. There is no indication that these substances will be espoused by the drug enthusiasts of the West as avidly as other ethno-psychopharmacological agents such as Peruvian coca leaf, the Indian hemp, the Asian poppy, or the American tobacco. The possibility, however, of some use in the West cannot be discounted.
New psychoactive substance α-PVP in a traffic accident case.

PubMed

Rojek, Sebastian; Kula, Karol; Maciów-Głąb, Martyna; Kłys, Małgorzata

The problems of new psychoactive substances (NPSs), especially related to drivers, constitute an open research area. In this case report, we present a traffic accident case, in which two passengers of five individuals died instantly, while the other three persons survived the accident with minor injuries only. From the blood samples of the driver and the passengers, α-pyrrolidinovalerophenone (α-PVP), an NPS belonging to the category of cathinone derivatives, was disclosed. Therefore, we established a detailed procedure for analysis of α-PVP in blood samples by liquid chromatography-tandem mass spectrometry. After careful validation tests of this method, α-PVP concentration in blood samples from the surviving driver and passengers, and from the two deceased, were measured. The concentrations varied from 20 to 650 ng/mL. Access to detailed information originating from the court files and from explanations provided by the driver and eye witnesses revealed extremely valuable illustrative details addressing the symptoms and pharmacological effects of α-PVP on the human organism, thus contributing to enriching the body of knowledge of α-PVP abuse.
High-affinity cannabinoid binding site in brain: A possible marijuana receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nye, J.S.

The mechanism by which delta{sup 9} tetrahydrocannabinol (delta{sup 9}THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5{prime}-Trimethylammonium-delta{sup 8}THC (TMA) is a positively charged analog of delta-{sup 8}THC modified on the 5{prime} carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of ({sup 3}H)-5{prime}-trimethylammonium-delta-{sup 8}THC (({sup 3}H)TMA) to rat neuronal membranes. ({sup 3}H)TMA binds saturably and reversibly to brain membranes with high affinity to apparently one classmore » of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of ({sup 3}H)TMA binding activity of approximately 60,000 daltons apparent molecular weight.« less
Acute behavioral effects of co-administration of mephedrone and MDMA in mice.

PubMed

Budzynska, Barbara; Michalak, Agnieszka; Frankowska, Małgorzata; Kaszubska, Katarzyna; Biała, Grażyna

2017-04-01

Abuse of more than one psychoactive drug is becoming a global problem. Our experiments were designed to examine the effects of a concomitant administration of 3,4-methylenedioxy-methamphetamine (MDMA) and mephedrone on depression- and anxiety-like behaviors and cognitive processes in Swiss mice. In order to investigate the drug interactions the forced swimming test (FST) - an animal model of depression, the passive avoidance (PA) test - a memory and learning paradigm, as well as the elevated plus maze (EPM) test - test for anxiety level were used. The results revealed that a concomitant administration of non-effective doses of mephedrone (1mg/kg) and MDMA (1mg/kg) exerted marked antidepressive effects in the FST. Also a co-administration of mephedrone (2.5mg/kg) and MDMA (1mg/kg) displayed a pro-cognitive action in the PA paradigm. Furthermore, even though mephedrone and MDMA can, in general, exert some anxiogenic effects in mice, the concomitant administration of nonactive doses of both drugs (0.05 and 0.1mg/kg, respectively) in the EPM test, did not show any synergistic effect in our study. The effects of mephedrone and MDMA combination on mammalian organisms were attempted to be evaluated in our study and the results are described in the present report. These results may help explain the reasons for and consequences of a concomitant administration of psychoactive substances with regards to the central nervous system, while being possibly useful in the treatment of polydrug intoxication. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.
Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly.

PubMed

Pacher, Pal; Steffens, Sabine; Haskó, György; Schindler, Thomas H; Kunos, George

2018-03-01

Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB 1 R and CB 2 R) has been implicated in a variety of cardiovascular pathologies. Activation of CB 1 R facilitates the development of cardiometabolic disease, whereas activation of CB 2 R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ 9 -tetrahydrocannabinol (THC), is an agonist of both CB 1 R and CB 2 R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB 1 R in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. In this Review, we summarize the role of the endocannabinoid system in cardiovascular disease, and critically discuss the cardiovascular consequences of marijuana and synthetic cannabinoid use. With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.
Patterns of drug use from adolescence to young adulthood: III. Predictors of progression.

PubMed Central

Yamaguchi, K; Kandel, D B

1984-01-01

Possible linkages of influence among classes of drugs in the observed sequential progression from adolescence to young adulthood are investigated through event history analyses. Three stages are examined: initiation to marijuana, to the use of other illicit drugs, and to prescribed psychoactive drugs. The data are based on a follow-up cohort of former adolescents representative of high school students in grade 10 and 11 in New York State who were reinterviewed nine years later at ages 24-25. The sequential order between alcohol and/or cigarettes and marijuana reflects not only the effect of the use of legal drugs on marijuana initiation, but also age effects on onset of these drugs, controlling for individual characteristics measured in adolescence; marijuana use by one's friends in adolescence is an additional important predictor of marijuana initiation. Prior use of marijuana is necessary for progression to other illicit drugs. Multiple factors are involved in the progression to prescribed drugs, with adolescent depressive symptomatology and use of other illicit drugs important for both sexes, and maternal use of psychoactive drugs, dropping out of school, and prior use of marijuana of additional importance for women. Although licit drugs influence initiation into marijuana independently of age effects, it is especially for the progression from marijuana to other illicit drugs that the earlier drug is associated with the progression to a higher stage drug. PMID:6742253
In vitro exposure of cultured porcine choroid plexus epithelial cells to immunosuppressant, anti-inflammatory, and psychoactive drugs.

PubMed

Emerich, Dwaine F; Schneider, Patricia; Bintz, Briannan; Hudak, Jebecka; Thanos, Christopher G

2007-01-01

Delivery of neurotrophic molecules to the CNS is a potential treatment for preventing the neuronal loss in neurological disorders such as Huntington's disease (HD). Choroid plexus (CP) epithelial cell transplants secrete several neurotrophic factors and are neuroprotective in rat and monkey animal models of HD. HD patients receiving CP transplants would likely receive a course of immunosuppressant/anti-inflammatory treatment postsurgery and would remain on psychoactive medications to treat their motor, psychiatric, and emotional symptoms. Therefore, we examined whether CP epithelial cells are impacted by incubation with cyclosporine A (CsA), dexmethasone, haloperidol, fluoxetine, and carbamezapine. In each case, DNA was quantified to determine cell number, a formazen dye-based assay was used to quantify cell metabolism, and vascular endothelial growth factor (VEGF) levels were measured as a marker of protein secretion. Except for the highest dose of fluoxetine, none of the drugs tested exerted any detrimental effect on cell number. Incubation with CsA or dexamethasone did not have any consistent significant effect on VEGF secretion or cell metabolism. Carbamazepine was without effect while only the highest dose of haloperidol tested modestly lowered cell metabolism. VEGF secretion and cell metabolism was not measurable from CP cells exposed to 100 microM fluoxetine. These data continue to support the potential use of CP transplants in HD.
Plant use in the medicinal practices known as "strict diets" in Chazuta valley (Peruvian Amazon).

PubMed

Sanz-Biset, Jaume; Cañigueral, Salvador

2011-09-01

Strict diets are traditional medicinal practices where plant remedies are consumed with nearly fasting and with some sort of social seclusion. The aim of this work was to describe these practices of Chazuta and the use of plants within, as well as to analyse the possible functions of the last. The information was obtained through interviews to the 6.3% of the district rural adult population (140 individuals, 75% of which was considered Quechua). In total, 122 strict diets were recorded and 106 different plant species were reported to be used. Strict diets present a characteristic structure and plant use. The main effects reported in strict diets were antinflammatory, antiinfective, brain function alteration and depuration. Strict diets are well structured traditional medicinal practices, also with a symbolic significance in the life cycle of chazutian men. Plants used in strict diets can contribute to the main effects through antinflammation, antiinfective actions, psychoactivity and depurative related activities. The correlation between literature evidence of activity of most used plants and effects reported for the correspondent diet (i.e. in which the plant was used) are 36% for antinflammatory activity, 29% for antimicrobial activity, 18% for psychoactivity and 5% for depurative related activities. The percentages go to 77%, 64%, 73% and 32%, respectively, when literature evidences on related taxa are also considered. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

PubMed

Malone, Daniel Thomas; Jongejan, Dennis; Taylor, David Alan

2009-08-01

While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity.
Dysregulated mTORC1-Dependent Translational Control: From Brain Disorders to Psychoactive Drugs

PubMed Central

Santini, Emanuela; Klann, Eric

2011-01-01

In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior. PMID:22073033
Engineering molecularly imprinted polymers (MIPs) for the selective extraction and quantification of the novel psychoactive substance (NPS) methoxphenidine and its regioisomers.

PubMed

Lowdon, J W; Alkirkit, S M O; Mewis, R E; Fulton, D; Banks, C E; Sutcliffe, O B; Peeters, M

2018-04-30

In this communication, we present the first developed Molecularly Imprinted Polymers (MIPs) for the specific detection of a New Psychoactive Substance (NPS); namely, methoxphenidine (MXP) and its regioisomers. Selectivity of the MIP towards MXP is studied by analysing mixtures and an acquired street sample with High Performance Liquid Chromatography coupled to UV detection. The study demonstrates that the engineered polymers selectively extract MXP from heterogeneous samples, which makes for a very powerful diagnostic tool that can detect traces of MXP in complicated NPS samples.
Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

PubMed Central

Wu, Ruiyong; Gao, Jun; Chou, Shinnyi; Davis, Collin; Li, Ming

2016-01-01

Summary As a highly motivated social behavior, maternal behavior in rats has been routinely used to study psychoactive drugs for clinical, neuroscience and pharmacological purposes. Recent evidence indicates that acute activation of serotonin 2C (5-HT2C) receptors causes a disruption of rat maternal behavior. The present study was designed to elucidate the behavioral, pharmacological mechanisms and neuroanatomical basis of this 5-HT2C effect. First, we replicated the finding that acute MK212 injection (2.0 mg/kg, a highly selective 5-HT2C agonist) disrupts maternal behavior, especially on pup retrieval. Interestingly, this disruption was significantly attenuated by 4-h pup separation (a procedure putatively increased maternal motivation). MK212 also suppressed food retrieval, indicating that it has a general effect on motivated behaviors. Second, we showed that MK212 disrupts maternal behavior by specifically activating 5-HT2C receptor, as pretreatment with a 5-HT2C receptor antagonist SB242084 (0.6 and 1.0 mg/kg) alleviated MK212-induced disruption on pup retrieval. Third, we microinjected MK212 into various brain regions implicated in the regulation of maternal behavior: nucleus accumbens shell (25, 75, 250 ng/0.5μl/side), medial prefrontal cortex (25 and 250 ng, 1, 2 and 5 μg/0.5μl/side), and medial preoptic area (MPOA, 75 ng, 1 and 5 μg/0.5μl/side). Pup retrieval and other maternal responses were not affected by any of these manipulations. Finally, we used c-Fos immunohistochemistry to identify the central mechanisms of the acute and repeated MK212 effects on maternal behavior. Acute MK212 (2.0 mg/kg) disrupted pup retrieval and concurrently decreased c-Fos expression in the ventral part of lateral septal nucleus (LSv), MPOA, dentate gyrus (DG) and dorsal raphe (DR), but increased it in the central amygdala (CeA). Five days of repeated MK212 (2.0 mg/kg) treatment produced a persistent disruption of pup retrieval and only decreased c-Fos expression in the DR. These findings not only confirm a role of 5-HT2C receptor in rat maternal behavior, but also suggest that the coordinated 5-HT2C activity in various limbic (e.g., LSv, DG, CeA), hypothalamic regions (e.g., MPOA) and brainstem areas (e.g. DR), is likely involved in the mediation of important psychological processes (e.g. motor function, motivation) necessary for the normal expression of maternal behavior. PMID:27566488
Behavioral, pharmacological and neuroanatomical analysis of serotonin 2C receptor agonism on maternal behavior in rats.

PubMed

Wu, Ruiyong; Gao, Jun; Chou, Shinnyi; Davis, Collin; Li, Ming

2016-11-01

As a highly motivated social behavior, maternal behavior in rats has been routinely used to study psychoactive drugs for clinical, neuroscience and pharmacological purposes. Recent evidence indicates that acute activation of serotonin 2C (5-HT 2C ) receptors causes a disruption of rat maternal behavior. The present study was designed to elucidate the behavioral, pharmacological mechanisms and neuroanatomical basis of this 5-HT 2C effect. First, we replicated the finding that acute MK212 injection (2.0mg/kg, a highly selective 5-HT 2C agonist) disrupts maternal behavior, especially on pup retrieval. Interestingly, this disruption was significantly attenuated by 4-h pup separation (a procedure putatively increased maternal motivation). MK212 also suppressed food retrieval, indicating that it has a general effect on motivated behaviors. Second, we showed that MK212 disrupts maternal behavior by specifically activating 5-HT 2C receptor, as pretreatment with a 5-HT 2C receptor antagonist SB242084 (0.6 and 1.0mg/kg) alleviated MK212-induced disruption on pup retrieval. Third, we microinjected MK212 into various brain regions implicated in the regulation of maternal behavior: nucleus accumbens shell (25, 75, 250ng/0.5μl/side), medial prefrontal cortex (25 and 250ng, 1, 2 and 5μg/0.5μl/side), and medial preoptic area (MPOA, 75ng, 1 and 5μg/0.5μl/side). Pup retrieval and other maternal responses were not affected by any of these manipulations. Finally, we used c-Fos immunohistochemistry to identify the central mechanisms of the acute and repeated MK212 effects on maternal behavior. Acute MK212 (2.0mg/kg) disrupted pup retrieval and concurrently decreased c-Fos expression in the ventral part of lateral septal nucleus (LSv), MPOA, dentate gyrus (DG) and dorsal raphe (DR), but increased it in the central amygdala (CeA). Five days of repeated MK212 (2.0mg/kg) treatment produced a persistent disruption of pup retrieval and only decreased c-Fos expression in the DR. These findings not only confirm a role of 5-HT 2C receptor in rat maternal behavior, but also suggest that the coordinated 5-HT 2C activity in various limbic (e.g., LSv, DG, CeA), hypothalamic regions (e.g., MPOA) and brainstem areas (e.g. DR), is likely involved in the mediation of important psychological processes (e.g. motor function, motivation) necessary for the normal expression of maternal behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.
An Assessment of Drug Education-Prevention Programs in the U. S. Army. Army Research Institute Technical Paper 261.

ERIC Educational Resources Information Center

Cook, Royer F.; Morton, Anton S.

In recent years the Army has been concerned about the widespread use of psychoactive drugs by all classes of young people and the effects of this use on the Army. In order to curb this use among soldiers the Army initiated a comprehensive program to prevent and control the abuse of alcohol and drugs. Prevention was considered to include education,…

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

PubMed

Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

2017-09-01

The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.
New Drugs on the Internet: The Case of Camfetamine

PubMed Central

Cinosi, Eduardo; Corazza, Ornella; Acciavatti, Tiziano; Martinotti, Giovanni; di Giannantonio, Massimo

2014-01-01

Introduction. The number of new psychoactive substances (NPS) advertised for sale online is constantly increasing and it has become a phenomenon of global concern. Among NPS, Camfetamine has been rediscovered as recreational drug in 2011. Very little information is still available in the scientific literature on its nature and potential health risks. Methods. Data in scientific literature were integrated with a multilingual qualitative assessment of a range of online resources over the period of 32 months (May 2011–January 2014). Results. N-Methyl-3-phenyl-norbornan-2-amine (Camfetamine) may act as an indirect dopaminergic agonist in the central nervous system and may have mild-moderate opioid activity too. There are no current epidemiological data about recreational use of Camfetamine; our research shows that it is indeed used especially by individuals with a history of recreational polydrug misuse. It facilitates mental alertness, induces relaxation, and, unlike many other stimulants, seems not to be associated with severe physical effects. Valid causes for concern issued in our research may be Camfetamine intravenous or intramuscular administration as well as its use in conjunction with other psychoactive substances. Conclusions. It is here highlighted that more large-scale studies need to be carried out to confirm and better describe both the extent of Camfetamine misuse and possible psychotropic/adverse effects. PMID:25136586
An overview of recent developments in the analytical detection of new psychoactive substances (NPSs).

PubMed

Smith, Jamie P; Sutcliffe, Oliver B; Banks, Craig E

2015-08-07

New psychoactive substances (NPSs), sometimes referred to as "legal highs" in more colloquial environments/the media, are a class of compounds that have been recently made available for abuse (not necessarily recently discovered) which provide similar effects to the traditional well studied illegal drugs but are not always controlled under existing local, regional or international drug legislation. Following an unprecedented increase in the number of NPSs in the last 5 years (with 101 substances discovered for the first time in 2014 alone) its, occasionally fatal, consequences have been extensively reported in the media. Such NPSs are typically marketed as 'not for human consumption' and are instead labelled and sold as plant food, bath salts as well as a whole host of other equally nondescript aliases in order to bypass legislative controls. NPSs are a new multi-disciplinary research field with the main emphasis in terms of forensic identification due to their adverse health effects, which can range from minimal to life threatening and even fatalities. In this mini-review we overview this recent emerging research area of NPSs and the analytical approaches reported to provide detection strategies as well as detailing recent reports towards providing point-of-care/in-the-field NPS ("legal high") sensors.
Psychometric Evaluation of the Substance Use Risk Profile Scale (SURPS) in an Inpatient Sample of Substance Users Using Cue-Reactivity Methodology

PubMed Central

Schlauch, Robert C.; Crane, Cory A.; Houston, Rebecca J.; Molnar, Danielle S.; Schlienz, Nicolas J.; Lang, Alan R.

2015-01-01

The current project sought to examine the psychometric properties of a personality based measure (Substance Use Risk Profile Scale; SURPS: introversion-hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) designed to differentially predict substance use preferences and patterns by matching primary personality-based motives for use to the specific effects of various psychoactive substances. Specifically, we sought to validate the SURPS in a clinical sample of substance users using cue reactivity methodology to assess current inclinations to consume a wide range of psychoactive substances. Using confirmatory factor analysis and correlational analyses, the SURPS demonstrated good psychometric properties and construct validity. Further, impulsivity and sensation-seeking were associated with use of multiple substances but could be differentiated by motives for use and susceptibility to the reinforcing effects of stimulants (i.e., impulsivity) and alcohol (i.e. sensation-seeking). In contrast, introversion-hopelessness and anxiety sensitivity demonstrated a pattern of use more focused on reducing negative affect, but were not differentiated based on specific patterns of use. Taken together, results suggests that among those receiving inpatient treatment for substance use disorders, the SURPS is a valid instrument for measuring four distinct personality dimensions that may be sensitive to motivational susceptibilities to specific patterns of alcohol and drug use. PMID:26052180
Extended Access Cocaine Self-Administration Results in Tolerance to the Dopamine-Elevating and Locomotor-Stimulating Effects of Cocaine

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Jones, Sara R.

2013-01-01

Tolerance to the neurochemical and psychoactive effects of cocaine after repeated use is a hallmark of cocaine addiction in humans. However, comprehensive studies on tolerance to the behavioral, psychoactive, and neurochemical effects of cocaine following contingent administration in rodents are lacking. We outlined the consequences of extended access cocaine self-administration as it related to tolerance to the psychomotor activating, dopamine (DA) elevating, and DA transporter (DAT) inhibiting effects of cocaine. Cocaine self-administration (1.5 mg/kg/inj; 40 inj; 5 days), which resulted in escalation of first hour intake, caused reductions in evoked DA release and reduced maximal rates of uptake through the DAT as measured by slice voltammetry in the nucleus accumbens core. Further, we report reductions in cocaine-induced uptake inhibition as measured by fast scan cyclic voltammetry, and a corresponding increase in the dose of cocaine required for 50% inhibition of DA uptake (Ki) at the DAT. Cocaine tolerance at the DAT translated to reductions in cocaine-induced DA overflow as measured by microdialysis. Additionally, cocaine-induced elevations in locomotor activity and stereotypy were reduced, while rearing behavior was enhanced in animals with a history of cocaine self-administration. Here we demonstrate both neurochemical and behavioral cocaine tolerance in an extended-access rodent model of cocaine abuse, which allows for a better understanding of the neurochemical and psychomotor tolerance that develops to cocaine in human addicts. PMID:24102293
The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects.

PubMed

Nóbrega, Leandro; Dinis-Oliveira, Ricardo Jorge

2018-05-01

New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U.S. National Library of Medicine) and governmental websites without limitation of the period. α-PVP is a wide spread and easy to get special type of synthetic cathinone with seemingly powerful cocaine-like stimulant effects, high brain penetration, high liability for abuse and with increased risk of adverse effects such as tachycardia, agitation, hypertension, hallucinations, delirium, mydriasis, self-injury, aggressive behavior, and suicidal ideations. α-PVP undergoes extensive metabolism via different pathways and the α-PVP itself or its metabolites β-hydroxy-α-PVP and α-PVP lactam represent the main targets for toxicological analysis in urine. There is a limited knowledge regarding the short- and long-term effects of α-PVP and metabolites, and pharmacogenetic influence, hence further clinical and forensic toxicological studies are required. Moreover, since α-PVP cannot be detected with classic routine analysis procedures, statements on the frequency of their consumption cannot be made.
Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.

PubMed

Wiley, Jenny L; Marusich, Julie A; Thomas, Brian F

2017-01-01

Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB 1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ 9 -tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB 1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.
Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents.

PubMed

Cha, Hye Jin; Jeon, Seo Young; Jang, Hwa Jin; Shin, Jisoon; Kim, Young-Hoon; Suh, Soo Kyung

2018-05-29

New psychoactive substances (NPSs), i.e., newly designed substances with chemical residues that are slightly different from those of known psychoactive substances, have been emerging since the late 2000s, and social problems related to the use of these substances are increasing globally. Two such NPSs are 4-chloro-2,5-dimethoxyamphetamine (DOC), a psychedelic substance that is structurally related to amphetamine, and AH-7921, an opioid analgesic that is used for recreational purposes and has a potency similar to that of morphine. Currently, scientific evidence for the dependence liability or toxicity of NPSs is lacking. Therefore, in this study, we performed animal behavioral tests to evaluate the dependence liability of DOC and AH-7921. The rewarding and reinforcing effects of DOC and AH-7921 were evaluated using the conditioned place preference (CPP) paradigm in mice and the self-administration (SA) procedure in rats. Both DOC and AH-7921 increased the preference for the drug-paired compartment in the CPP test at a dose of 0.3 mg/kg and increased the number of responses to the active lever in the SA test at 0.01 mg/(kg·infusion). Collectively, the data suggest that DOC and AH-7921 may have both rewarding and reinforcing effects. Further studies are needed to confirm the reinforcing effects in broader dose ranges with various schedules. Copyright © 2018 Elsevier B.V. All rights reserved.
Overcoming the barriers to effective treatment for attention-deficit/hyperactivity disorder: a neuro-educational approach.

PubMed

Monastra, Vincent J

2005-10-01

Despite specific diagnostic criteria, published practice guidelines for assessing patients, and the availability of effective pharmacological treatments for children diagnosed with attention-deficit/hyperactivity disorder (AD/HD), a review of prescription practices in the United States indicates that as few as 25-50% of these patients receive even minimal medical treatment for this condition. Because untreated children with AD/HD are at increased risk for psychoactive substance abuse, criminal behavior, and other social problems as adults, the provision of effective care during childhood is essential. In order to clarify the factors impeding treatment during childhood and develop a targeted intervention to overcome these barriers, two studies involving 1514 families were conducted. Each family included one child diagnosed with AD/HD. Factors associated with treatment failure or non-compliance with medical advice included: dissatisfaction with a diagnostic process limited to brief observation, interview, and review of behavior rating scales; fear of stimulant medication; lack of medication response within the first month; development of side-effects during the first month; lack of understanding of the reasons stimulants were being prescribed for a child, and insufficient clinical response. Based on these findings, an intervention program consisting of a comprehensive evaluation process (that included neuropsychological and neurophysiological tests of attention, and medical screening for other health problems associated with inattention and hyperactivity) and parent education about the medical causes of AD/HD, the biochemical action of medications, the relationship between dietary habits and attention, and the educational rights of children with AD/HD was conducted. Following completion of this three session intervention, 95% of patients complied with medical recommendations, initiated pharmacological treatment, and continued medication for a 2-year follow-up period. Three percent of the patients were diagnosed and treated for other medical conditions.
A new psychoactive 5H-2,3-benzodiazepine with a unique spectrum of activity.

PubMed

Horváth, K; Andrási, F; Berzsenyi, P; Pátfalusi, M; Patthy, M; Szabó, G; Sebestyén, L; Bagdy, E; Körösi, J; Botka, P

1989-08-01

The neuropharmacological effects of 1-(4-amino-phenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine (GYKI 52 322) were investigated and compared with those of chlordiazepoxide and chlorpromazine. This novel 2,3-benzodiazepine displays neuroleptic activity in the apomorphine-climbing (ED50 = 1.15 mg/kg i.p.) and swim-induced grooming (ED50 = 6.9 mg/kg i.p.) tests in mice and it inhibits the conditioned avoidance response in rats (ED50 = 8.2 mg/kg i.p. and 9.8 mg/kg p.o.). However, it does not antagonize apomorphine-evoked vomiting in dogs; or stereotypy, hypermotility and turning in rats even at as high a dose as 50 mg/kg i.p. On the other hand it is active in the hole board test in mice (MED (minimal effective dose) = 0.5 mg/kg i.p.) and in the lick conflict assay in rats (MED = 5 mg/kg i.p.), indicating anxiolytic property. It shows antiaggressive effect in the fighting mice test (ED50 = 8.1 mg/kg p.o.) and the carbachol-rage procedure in cats (active at 10 mg/kg i.p.) According to the biochemical findings, this compound does not bind to the central dopamine receptors (IC50 greater than 10(-4) mol/l), but it shows affinity to the 5-HT1 receptors (IC50 = 7.1 x 10(-6) mol/l) and inhibits brain cAMP-phosphodiesterase (IC50 = 2.4 x 10(-5) mol/l). The substance causes no elevation of dopamine turnover and serum prolactin level suggesting fewer side effects. So the term "atypical neuroleptic agent" is proposed to characterize this molecule.
[Can one talk of benzodiazepine "drunkenness"? About acute benzodiazepine intoxication, without suicidal or mortiferous tendencies].

PubMed

Menecier, P; Texier, M A; Las, R; Ploton, L

2012-02-01

When we refer to "drunkenness", more often than not, we think of alcohol or cannabis being the instigator rather than pharmacological drugs, even if outside the toxic origins, "drunkenness" may also occur without any substance intake: one can be drunk on love, poetry, music and even mania. Benzodiazepine "drunkenness" is not a classical notion in medicine. But the concept of addictology allows one to enlarge different approaches and to consider the relationship with psychoactive substances according to the same references. So, in a single fashion, between use and misuse, is it possible to resort to the same concepts for pharmacological drugs, including "drunkenness"? Any intake of a psychoactive substance, limited in time, which will take the consumer some time to recover from, can be called simple use, intoxication or drunkenness. Intoxication is rather a classical medical concept linked with poisoning, and hence the toxicological aspects prevail particularly through the concept of a toxidrome. However, little research has been done on "drunkenness" in other medical aspects, neither psychological aspects nor sociological aspects. If poisoning is defined as soon as a poison is introduced into the body, the intoxication arises after a threshold (that toxicology usually defines), but no means are available to measure the onset of the inebriation, neither any ingested amounts nor any toxic concentration in the body. It is hard to define "drunkenness" simply. At first, it is most often seen as a pathology in medicine, unlike in every day life. "Drunkenness" can be the result of physiological disturbances, notably through the effects of substances and can therefore be the manifestation of a cerebral dysfunction. Alternatively, it can arise from a variation of emotional or sensorial stimuli. If the feelings associated with drunkenness are positive and pleasant a repetition will occur in the search to reproduce enjoyable effects in reference to neurophysiological models of reward systems of the brain, and can tend to be limited to a search for pleasure. Moreover, "drunkenness" may be considered as a leak, a regression or a kind of renouncement. It may sometimes be a search for sedation, for conscious sleep, or to avoid reality. And, finally, "drunkenness" may be suicidal. Since the launch of benzodiazepines on the market during the sixties, their prescription has developed, making them so readily available in France that they are nearly as easy to obtain as alcohol. The widespread diffusion of these psychoactive substances, obtained with or without medical prescription, renders them one of the principle means of chemically modulating thought and consciousness that has become accessible to all. One of the first reasons for this is the easy and wide prescription of these drugs by almost all practitioners. Choosing between benzodiazepines or alcohol (or associating both substances) is not fortuitous. Besides intoxication with pharmacological drugs, whether voluntary or otherwise, medication overdose and iatrogenic effects, there is an incidence of a substantial use of over the counter psychoactive drugs in order to trigger other effects than suicide or self-harm. This use of pharmacological drugs, sometimes referred to as "entertaining", can lead to massive intake with dramatic behavioural response. Is it then possible to use the same term "drunkenness" for a pharmacological drug-induced state as for a state provoked by other psychoactive substances with addictive potential ? The clinical presentation of benzodiazepine "drunkenness" resembles the pharmacological effects of these drugs. If we link alcoholic and benzodiazepine "drunkenness", we can draw a parallel between the properties, the action mechanisms, the effects and the risks incurred by the consumption of these two classes of psychotropics. The similarities concern the existence of a preclinical phase, of the same biochemical or neurophysiological basis, of the same properties, notably complex relationships with anxiety. They also have the same amnesiac effects, possible paradoxical effects, or sedation potentialities that may lead to coma, respiratory depression and death. But differences exist for benzodiazepines, in the lack of disinhibition effects, the lack of cerebellar effects, the variability of elimination kinetics according to the molecules, the rarity or the lack of "recreational" intakes, and the lack of easy blood level measurements. An attempt is made to outline the definition of benzodiazepine "drunkenness", including sociological, psychological, and medical dimensions beyond the sole toxicological aspects. So, studying the misuse of benzodiazepines in more detail including the acute effects such as "drunkenness", except suicidal or mortiferous tendencies, can allow further development of its recognition, screening and prevention. Copyright Â© 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.
Success rates in smoking cessation: Psychological preparation plays a critical role and interacts with other factors such as psychoactive substances.

PubMed

Joly, Bertrand; Perriot, Jean; d'Athis, Philippe; Chazard, Emmanuel; Brousse, Georges; Quantin, Catherine

2017-01-01

The aim of this study was to identify factors associated with the results of smoking cessation attempts. Data were collected in Clermont-Ferrand from a smoking cessation clinic between 1999 and 2009 (1,361 patients). Smoking cessation was considered a success when patients were abstinent 6 months after the beginning of cessation. Multivariate logistic regression was used to investigate the association between abstinence and different factors. The significant factors were a history of depression (ORadjusted = 0.57, p = 0.003), state of depression at the initial consultation (ORa = 0.64, p = 0.005), other psychoactive substances (ORa = 0.52, p<0.0001), heart, lung and Ear-Nose-Throat diseases (ORa = 0.65, p = 0.005), age (ORa = 1.04, p<0.0001), the Richmond test (p<0.0001; when the patient's motivation went from insufficient to moderate, the frequency of abstinence was twice as high) and the Prochaska algorithm (p<0.0001; when the patient went from the 'pre-contemplation' to the 'contemplation' level, the frequency of success was four times higher). A high score in the Richmond test had a greater impact on success with increasing age (significant interaction: p = 0.01). In exclusive smokers, the contemplation level in the Prochaska algorithm was enough to obtain a satisfactory abstinence rate (65.5%) whereas among consumers of other psychoactive substances, it was necessary to reach the preparation level in the Prochaska algorithm to achieve a success rate greater than 50% (significant interaction: p = 0.02). The psychological preparation of the smoker plays a critical role. The management of smoking cessation must be personalized, especially for consumers of other psychoactive substances and/or smokers with a history of depression.
The relationship between physical maltreatment and substance use among adolescents: a survey of 95,788 adolescents in Hong Kong.

PubMed

Lau, Joseph T F; Kim, Jean H; Tsui, Hi-Yi; Cheung, Albert; Lau, Mason; Yu, Aaron

2005-08-01

To determine the prevalence of corporal punishment and the infliction of injuries from a beating occurring without provocation in the previous 6 months among secondary school children in Hong Kong, and to examine the associations between these two forms of physical maltreatment with substance-use-related behaviors and attitudes. Using secondary data, a cross-sectional, self-administered, anonymous survey of 95,788 secondary school students was conducted in Hong Kong. The prevalence of physical maltreatment showed statistically significant associations with younger age, attendance in Chinese-speaking day schools, temporary housing, residence with only one parent, poorer parental relationship, greater peer influence, perceptions of excessive academic pressure, and feelings of being blamed for poor academic performance. Adolescents who had experienced corporal punishment were more likely to be current users of alcohol (OR = 1.11), tobacco (OR = 1.31), psychoactive substances (OR = 1.60), or heroin (OR = 1.90). Those who had been beaten to injury by a family member without provocation within the past 6 months also were more likely to be current users of alcohol (OR = 1.35), tobacco (OR = 1.65), psychoactive substances (OR = 2.39), and heroin (OR = 3.07). Additionally, students who experienced physical maltreatment were more likely to be acquainted with habitual substance users, have better access to psychoactive substances, to have engaged in sex after abusing drugs, have obtained money from illegal sources to purchase drugs, and believe that psychoactive substances are not harmful or addictive. Physical maltreatment showed strong associations with drug-related behaviors and attitudes, after adjusting for potential confounders. Further longitudinal studies are required to understand the causal direction of the relationship.
Acute health problems due to recreational drug use in patients presenting to an urban emergency department in Switzerland.

PubMed

Liakoni, Evangelia; Dolder, Patrick C; Rentsch, Katharina; Liechti, Matthias E

2015-01-01

To describe acute toxicity of recreational drugs including novel psychoactive substances. We included all cases presenting at the emergency department (ED) of the University Hospital of Basel, Switzerland, between October 2013 and September 2014 with acute toxicity due to self-reported recreational drug use or with symptoms/signs consistent with acute toxicity. Isolated ethanol intoxications were excluded. Intoxications were confirmed with immunoassays and liquid chromatography coupled with mass spectrometry (LC-MS/MS), which also detected novel psychoactive substances. Among the 47,767 attendances at the ED, 216 were directly related to acute toxicity of recreational drugs. The mean patient age was 31 years and 69% were male. Analytical drug confirmation was available in 180 cases. Most presentations were related to cocaine (36%), cannabis (31%), opioids (13%), 3,4-methylenedioxy-methamphetamine (MDMA, 9%), other amphetamines (7%), benzodiazepines (7%), and lysergic acid diethylamide (LSD, 5%). The substances most commonly detected analytically were cannabis (37%), cocaine (33%), opioids (29%), benzodiazepines (21%), and amphetamines including MDMA (13%). Notably, there were only two cases of novel psychoactive substances (2,5-dimethoxy-4-bromophenethylamine [2C-B] and pentylone). The most frequent symptoms were tachycardia (31%), anxiety (27%), nausea or vomiting (23%), and agitation (22%). Severe complications included myocardial infarction (2), psychosis (10), seizures (10), and 1 fatality. Most patients were discharged home (68%), 8% were admitted to intensive care and 9% were referred to psychiatric care. Medical problems related to illicit drugs mostly concerned cocaine and cannabis and mainly involved sympathomimetic toxicity and/or psychiatric disorders. ED presentations associated with novel psychoactive substances appeared to be relatively rare.
[Chemical analysis of wastewater as a new way of monitoring drugs and medicines consumption at workplace].

PubMed

Wiergowski, Marek; Sołtyszewski, Ireneusz; Sein Anand, Jacek

2015-01-01

The available information on the quality and frequency of illegal psychoactive substances used or medicines misused by workers, are often out of date at the time of its publication. This is due to the dynamic introduction of new synthetic drugs on the black market, changes in trends in the recreational use of medicines and the lack of readily available and reliable tests for fast identification. Strategy for detection of narcotic and non-medical psychoactive drugs use at workplace should embrace all possible sources of information. Classical sources of information on the use of psychoactive substances at the workplace include: statistical data (general information on trends and magnitude of drug and medicine addiction collected by the Polish National Police, the National Bureau for Drug Prevention and emergency medical services), surveys, psychomotor tests and qualitative and quantitative analyses of biological material. Of the new and promising methods, used throughout the world in recent years, chemical-toxicological analysis of surface water and wastewater deserve special mention. An increasing interest in the study of urban waste water can significantly complement the source of knowledge about drug and medicine addiction using obtainable conventional methods. In recent years, a municipal wastewater analysis has become a new and very promising way of collecting updated information on the use of psychoactive substances and medicines. It seems that this kind of study may play an important role in the ongoing monitoring of drug and/or medicines use by selected groups of population (e.g., students, military, firemen, policemen, etc.). This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.
Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances.

PubMed

Bäckberg, Matilda; Jönsson, Karl-Henrik; Beck, Olof; Helander, Anders

2018-02-01

The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products. Copyright © 2017 John Wiley & Sons, Ltd.
[General characteristics of psychoactive substances consumption and abuse among high school population].

PubMed

Radovanović, Snezana; Milić, Caslav; Kocić, Sanja

2010-01-01

Consumption of psychoactive substances among the youth is suggestive of a trend indicating an accelerated and continual growth of the tendency in question. This research was aimed at investigating the frequency of psychoactive substance consumption among high school students on the territory of the town of Kragujevac so that the adequate measures on prevention could be taken. Data from the questionnaire answered by high school student attending the 1st and 4th grade of the medical, technical and economic high schools in Kragujevac were thereby used. The survey included the overall number of 1280 students: there were 793 (62%) male participants and 487 (38%) female. The research was conducted from October 2007 until January 2008. The questionnaire from the project "Health Status, Health Needs and Utilization of Health Care of the Population of Serbia" conducted by the Institute of Public Health of Serbia "Dr Milan Jovanović Batut" in 2000 was used in the survey. According to the answers, alcohol was used by 45.5%, cigarettes by 20% and drugs by 3.1% of the examined subjects. Following the use of alcohol and cigarettes, the most often used psychoactive substance was cannabis, which was consumed by 7.8% of the examined subjects out of who 9.8% were boys and 4.8% were girls. Since the risky behaviour seems not to be isolated and individual but rather as a combination of several forms of it, school programmes should treat young people before certain forms of behaviour are established. Family, school, health service and society should work on an organized basis as well as methodically on prevention and on fighting against these inadequate habits.
Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

PubMed Central

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-01-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30–5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of ‘High', ‘Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis. PMID:26708108
Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis.

PubMed

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-07-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of 'High', 'Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.
I like the old stuff better than the new stuff? Subjective experiences of new psychoactive substances.

PubMed

Matthews, Allison; Sutherland, Rachel; Peacock, Amy; Van Buskirk, Joe; Whittaker, Elizabeth; Burns, Lucinda; Bruno, Raimondo

2017-02-01

Over the past decade, monitoring systems have identified the rapid emergence of new psychoactive substances (NPS). While the use of many NPS is minimal and transitory, little is known about which products have potential for capturing the attention of significant proportions of the drug consuming market. The aim of this study was to explore self-reported experiences of three commonly used NPS classes within the Australian context (synthetic cathinones, hallucinogenic phenethylamines and hallucinogenic tryptamines) relative to traditional illicit drug counterparts. Frequent psychostimulant consumers interviewed for the Australian Ecstasy and related Drugs Reporting System (EDRS) (n=1208) provided subjective ratings of the pleasurable and negative (acute and longer-term) effects of substances used in the last six months on the last occasion of use, and the likelihood of future use. Stimulant-type NPS (e.g., mephedrone, methylone) were rated less favourably than ecstasy and cocaine in terms of pleasurable effects and likelihood of future use. DMT (a hallucinogenic tryptamine) showed a similar profile to LSD in terms of pleasurable effects and the likelihood of future use, but negative effects (acute and comedown) were rated lower. Hallucinogenic phenethylamines (e.g., 2C-B) showed a similar negative profile to LSD, but were rated as less pleasurable and less likely to be used again. The potential for expanded use of stimulant-type NPS may be lower compared to commonly used stimulants such as ecstasy and cocaine. In contrast, the potential of DMT may be higher relative to LSD given the comparative absence of negative effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Phylogenetic relationship of psychoactive fungi based on rRNA gene for a large subunit and their identification using the TaqMan assay (II).

PubMed

Maruyama, Takuro; Kawahara, Nobuo; Yokoyama, Kazumasa; Makino, Yukiko; Fukiharu, Toshimitsu; Goda, Yukihiro

2006-11-10

"Magic mushroom (MM)" is the name most commonly given to psychoactive fungi containing the hallucinogenic components: psilocin (1) and psilocybin (2). We investigated the rRNA gene (internal transcribed spacer (ITS) and large subunit (LSU)) of two Panaeolus species and four Psilocybe species fungi (of these, two are non-psilocybin species). On the basis of sequence alignment, we improved the identification system developed in our previous study. In this paper, we describe the new system capable of distinguishing MMs from non-psilocybin Psilocybe species, its application data and the phylogeny of MM species.
Psychedelic Fauna for Psychonaut Hunters: A Mini-Review.

PubMed

Orsolini, Laura; Ciccarese, Michela; Papanti, Duccio; De Berardis, Domenico; Guirguis, Amira; Corkery, John M; Schifano, Fabrizio

2018-01-01

Currently different classes of psychoactive substances are easily available for abuse, including several hundred novel psychoactive substances (NPS). Some of these drugs occur naturally in plants and animals or are chemically modified from plant or animal compounds and have been abused by humans over millennia. Recently, the occurrence of a new "drug culture" (e.g., psychonauts) who consume a great variety of NPS with hallucinogenic/psychedelic properties, facilitated the development of a new "psychedelic trend" toward the consumption of substances contained in some species of animals ("psychedelic fauna"). The present review aims at providing an overview of the most commonly abused "psychedelic animals," by combining a dual search strategy coming from online psychonauts' experiences and English literature searches on the PubMed/Medline Google Scholar databases. A multilingual qualitative assessment on a range of websites and online resources was performed in order to identify a list of animals who possess some psychoactive properties and could be abused by humans for recreational purposes. Several species are implicated (i.e., ants, amphibians, fish). Routes of administration depend on the animal, substance included, metabolism, toxicity and individual, social and cultural variability. Online purchase and access are easy through tourism-related search strategies (" frog trip ," " help of charmer snake," " religious trip ").
Regulating khat--dilemmas and opportunities for the international drug control system.

PubMed

Klein, Axel; Beckerleg, Susan; Hailu, Degol

2009-11-01

The regulation of khat, one of the most recent psychoactive drugs to become a globally traded commodity, remains hotly contested within different producer and consumer countries. As regimes vary, it has been possible to compare khat policies in Africa, Europe and North America from different disciplinary perspectives. Field research was conducted in East Africa and Europe, using a combination of semistructured interviews, participant observation and the analysis of trade statistics. The research established the significance of khat for rural producers, regional economies, as a tax base and source of foreign exchange. At the same time, khat as a psychoactive substance is associated with health and public safety problems that in turn are met with often ill-informed legislative responses. Bans have in turn lead to the criminalisation of users and sellers and illegal drug markets. The empirical work from Africa provides a strong argument for promoting evidence-based approaches to khat regulation, harnessing the positive aspects of the khat economy to develop a control model that incorporates the voices and respects the needs of rural producers. Ultimately, the framework for khat may provide both a model and an opportunity for revising the international treaties governing the control of other plant psychoactive-based substances.
'Ivory wave' toxicity in recreational drug users; integration of clinical and poisons information services to manage legal high poisoning.

PubMed

Murray, Douglas B; Potts, Stephen; Haxton, Carole; Jackson, Gillian; Sandilands, Euan A; Ramsey, John; Puchnarewicz, Malgorzata; Holt, David W; Johnston, Atholl; Nicholas Bateman, D; Dear, James W

2012-02-01

Novel psychoactive substances or 'legal highs' can be defined as psychoactive substances that have been developed to avoid existing drug control measures. Consistency of name, but with change in the content of the product, may cause harm. This could result in clusters of users being poisoned and developing unexpected physical and psychiatric symptoms. We describe such an event and the clinical phenotypes of a cluster of patients poisoned with a novel psychoactive substance in 'ivory wave' and analyze data from the National Poisons Information Service (NPIS) to estimate use across the United Kingdom. In addition, the likely active ingredient in this cluster of 'ivory wave' poisonings was identified. An analysis of consecutive patients attending the Royal Infirmary of Edinburgh emergency department in July and August 2010 with self-reported 'ivory wave' use was performed. Over a similar time frame, poisons enquiries regarding 'ivory wave' to the UK NPIS, by telephone and via the internet-based TOXBASE(®) poisons database ( www.toxbase.org ), were analyzed. A sample of 'ivory wave' powder and biological fluids from poisoned patients were investigated to determine the active ingredient. Thirty four emergency attendances due to 'ivory wave' toxicity were identified. The mean +/- SD (range) age was 28.6 +/- 7.8 (16-44) years. Patients demonstrated a toxidrome which lasted several days, characterized by tachycardia (65%), tachypnoea (76%), dystonia (18%), rhabdomyolysis (96%), leucocytosis (57%), agitation (62%), hallucinations (50%), insomnia (32%) and paranoia (21%). Enquiries to NPIS suggest that 'ivory wave' poisoning occurred throughout the United Kingdom. A sample of 'ivory wave' powder was analyzed and found to contain desoxypipradrol, which was also identified in biological fluids from 4 out of 5 patients tested. A cluster of cases presenting after use of a novel psychoactive substance was identified in Edinburgh and desoxypipradrol was identified as the likely cause. It was associated with prolonged psychiatric symptoms as a key feature. This chemical was regulated in response to the wider UK outbreak, which NPIS data suggest was geographically widespread but probably short lived. Novel psychoactive substances can produce significant toxicity and data from poisons centres may be used to indirectly detect new 'legal highs' that are causing clinical toxicity.
Cardiomyopathy from 1,1-Difluoroethane Inhalation.

PubMed

Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

2016-10-01

Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.
Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Burton, Page; Mechoulam, Raphael

2004-01-01

Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.
Medical use of cannabis. Cannabidiol: a new light for schizophrenia?

PubMed

Deiana, Serena

2013-01-01

The medical properties of cannabis have been known for many centuries; its first documented use dates back to 2800 BC when it was described for its hallucinogenic and pain-relieving properties. In the first half of the twentieth century, a number of pharmaceutical companies marked cannabis for indications such as asthma and pain, but since then its use has sharply declined, mainly due to its unpredictable effects, but also for socio-political issues. Recently, great attention has been directed to the medical properties of phytocannabinoids present in the cannabis plant alongside the main constituent Δ⁹-Tetrahydrocannabinol (THC); these include cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV). Evidence suggests an association between cannabis and schizophrenia: schizophrenics show a higher use of marijuana as compared to the healthy population. Additionally, the use of marijuana can trigger psychotic episodes in schizophrenic patients, and this has been ascribed to THC. Given the need to reduce the side effects of marketed antipsychotics, and their weak efficacy on some schizophrenic symptoms, cannabinoids have been suggested as a possible alternative treatment for schizophrenia. CBD, a non-psychoactive constituent of the Cannabis sativa plant, has been receiving growing attention for its anti-psychotic-like properties. Evidence suggests that CBD can ameliorate positive and negative symptoms of schizophrenia. Behavioural and neurochemical models suggest that CBD has a pharmacological profile similar to that of atypical anti-psychotic drugs and a clinical trial reported that this cannabinoid is a well-tolerated alternative treatment for schizophrenia. Copyright © 2012 John Wiley & Sons, Ltd.
An evaluation of the parents under pressure programme: a study protocol for an RCT into its clinical and cost effectiveness.

PubMed

Barlow, Jane; Sembi, Sukhdev; Gardner, Frances; Macdonald, Geraldine; Petrou, Stavros; Parsons, Helen; Harnett, Paul; Dawe, Sharon

2013-07-11

Many babies in the UK are born to drug-dependent parents, and dependence on psychoactive drugs during the postnatal period is associated with high rates of child maltreatment, with around a quarter of these children being subject to a child protection plan. Parents who are dependent on psychoactive drugs are at risk of a wide range of parenting problems, and studies have found reduced sensitivity and responsiveness to both the infant's physical and emotional needs. The poor outcomes that are associated with such drug dependency appear to be linked to the multiple difficulties experienced by such parents.An increase in understanding about the crucial importance of early relationships for infant well-being has led to a focus on the development and delivery of services that are aimed at supporting parenting and parent-infant interactions. The Parents under Pressure (PuP) programme is aimed at supporting parents who are dependent on psychoactive drugs or alcohol by providing them with methods of managing their emotional regulation, and of supporting their new baby's development. An evaluation of the PuP programme in Australia with parents on methadone maintenance of children aged 3 to 8 years found significant reductions in child abuse potential, rigid parenting attitudes and child behaviour problems. The study comprises a multicentre randomised controlled trial using a mixed-methods approach to data collection and analysis in order to identify which families are most able to benefit from this intervention.The study is being conducted in six family centres across the UK, and targets primary caregivers of children less than 2.5 years of age who are substance dependent. Consenting participants are randomly allocated to either the 20-week PuP programme or to standard care.The primary outcome is child abuse potential, and secondary outcomes include substance use, parental mental health and emotional regulation, parenting stress, and infant/toddler socio-emotional adjustment scale. This is one the first UK studies to examine the effectiveness of a programme targeting the parenting of substance-dependent parents of infants and toddlers, in terms of its effectiveness in improving the parent-infant relationship and reducing the potential for child abuse. International Standard Randomised Controlled Trial Number Register: ISRCTN47282925.
Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

PubMed

Gouzoulis-Mayfrank, E; Schreckenberger, M; Sabri, O; Arning, C; Thelen, B; Spitzer, M; Kovar, K A; Hermle, L; Büll, U; Sass, H

1999-06-01

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.
The interest in eight new psychoactive substances before and after scheduling.

PubMed

Ledberg, Anders

2015-07-01

In recent years the recreational use of new psychoactive substances (NPS) has increased. NPS are considered a threat to public health and the main response to this threat is to make the selling and buying of these substances illegal. In Sweden, during the last 5 years, 62 new substances have been classified as narcotics but little is known of the effects of making a particular substance illegal. The aim of this work is to study how legal status influences the interest in NPS in Sweden. Forty-five thousand posts made in a Swedish Internet discussion forum (Flashback Forum) related to eight NPS (MDPV, Methylone, 4-MEC, 4-HO-MET, MXE, 6-APB, AH-7921, and 3-MMC) were used to derive time-dependent measures of interest in these substances. Intervention analyses were used to investigate the effects of legal status on the forum interest. For all eight substances the activity on the forum (measured as number of posts per day) showed a drastic decrease around the time of classification. The statistical analysis showed that in seven of eight cases, the drop in activity could be accounted for by the legal status of the substances. The legal status of the substances was shown to have a substantial effect on the interest in the substances. The novel measure used to trace the interest in particular NPS could be a useful tool to follow trends in substance use in almost real-time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
MDPV and α-PVP use in humans: The twisted sisters.

PubMed

Karila, Laurent; Lafaye, Geneviève; Scocard, Amandine; Cottencin, Olivier; Benyamina, Amine

2018-05-15

The new psychoactive substances phenomenon continues to represent a considerable public health challenge. Synthetic cathinones are β-keto amphetamine analogues, also known as legal highs, research chemicals, bath salts. These drugs have surfaced as a popular alternative to other illicit drugs of abuse, such as cocaine, MDMA, and methamphetamine, due to their potent psychostimulant and empathogenic effects. Pyrovalerone cathinones (a-pyrrolidinophenones) form a distinct group of designer cathinones, such as MDPV. After being listed as an illegal product, "second generation" compounds such as α-PVP, sharing a very similar chemical structure with MDPV, were developed. Clinical effects of these compounds are individual, dose- and route of administration-dependent. Both of them have been involved in an increased number of, not only acute intoxications but also fatalities over the past few years, raising concerns in the medical field. In this paper, we will review the available data regarding the use and effects of MDPV and α-PVP in humans in order to highlight their impact on public health. Health actors and general population need to be clearly informed of potential risks and consequences of these 2 novel psychoactive substances spread and use. The literature search conducted led to the identification of potentially 83 relevant articles. All articles were screened from their abstracts to determine their relevance in the framework of the current review. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' Copyright © 2017 Elsevier Ltd. All rights reserved.
Psychoactive effects of tasting chocolate and desire for more chocolate.

PubMed

Nasser, Jennifer A; Bradley, Lauren E; Leitzsch, Jessica B; Chohan, Omar; Fasulo, Kristy; Haller, Josie; Jaeger, Kristin; Szulanczyk, Benjamin; Del Parigi, Angelo

2011-07-25

The purpose of this study was to characterize the psychoactive effects of tasting chocolate and to evaluate the contribution of the main chocolate components to the desire to consume more of it. A total of 280 participants, (F-155; M=125) ranging in age from 18-65, completed the study. Participants were randomly assigned to taste 12.5 g of either white chocolate ("control") or one of four chocolate ("cocoa") samples varying in sugar, fat and percent cocoa content, then answered the question: "Do you want more of this chocolate?" and "If yes, how many more pieces of this chocolate would you like to eat?" They completed pre- and post-consumption surveys, consisting of 30 questions derived from the Addiction Research Center Inventory (ARCI) subscales, Morphine-Benzedrine Group (MBG), Morphine (M) and Excitement (E). Significant decreases in post-pre consumption changes in MBG subscale were observed between the control sample and the 70% cocoa (p=0.046) or the 85% cocoa sample (p=0.0194). Proportionally more men than women wanted more of the tasted chocolate (p=0.035). Participants were more likely to want more of the tasted chocolate if they displayed a greater change in the MBG scale, and if their chocolate sample had high sugar and cocoa content, as assessed by multiple logistic regression. Our results suggest that multiple characteristics of chocolate, including sugar, cocoa and the drug-like effects experienced, play a role in the desire to consume chocolate. Copyright © 2011 Elsevier Inc. All rights reserved.
Medicinal use of cannabis: history and current status.

PubMed

Kalant, H

2001-01-01

To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids. The literature on therapeutic uses of cannabis and cannabinoids was assessed with respect to type of study design, quality and variability of data, independent replications by the same or other investigators, magnitude of effects, comparison with other available treatments and reported adverse effects. The results of this review were also compared with those of major international reviews of this topic in the past five years. Pure tetrahydrocannabinol and several analogues have shown significant therapeutic benefits in the relief of nausea and vomiting, and stimulation of appetite in patients with wasting syndrome. Recent evidence clearly demonstrates analgesic and anti-spasticity effects that will probably prove to be clinically useful. Reduction of intraocular pressure in glaucoma and bronchodilation in asthma are not sufficiently strong, long lasting or reliable to provide a valid basis for therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently promising to warrant further properly designed clinical trials. There is still a major lack of long term pharmacokinetic data and information on drug interactions. For all the present and probable future uses, pure cannabinoids, administered orally, rectally or parenterally, have been shown to be effective, and they are free of the risks of chronic inflammatory disease of the airways and upper respiratory cancer that are associated with the smoking of crude cannabis. Smoking might be justified on compassionate grounds in terminally ill patients who are already accustomed to using cannabis in this manner. Future research will probably yield new synthetic analogues with better separation of therapeutic effects from undesired psychoactivity and other side effects, and with solubility properties that may permit topical administration in the eye, or aerosol inhalation for rapid systemic effect without the risks associated with smoke inhalation.
Medical marijuana in neurology.

PubMed

Benbadis, Selim R; Sanchez-Ramos, Juan; Bozorg, Ali; Giarratano, Melissa; Kalidas, Kavita; Katzin, Lara; Robertson, Derrick; Vu, Tuan; Smith, Amanda; Zesiewicz, Theresa

2014-12-01

Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ(9)-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS 'depressants' and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand.
[Amotivational syndrome in organic solvent abusers].

PubMed

Ozaki, S; Wada, K

2001-01-01

Amotivational syndrome is a chronic psychiatric disorder characterized by a variety of changes in personality, emotions and cognitive functions such as lack of activity, inward-turning, avolition, apathy, incoherence, blunted affect, inability to concentrate and memory disturbance. The syndrome was first described among those patients with a history of longtime cannabis use in the 1960's. Since then, there have been several reports describing similar psychiatric disorders to amotivational syndrome among patients with the history of some other psychoactive substances use including solvents, methamphetamine and OTC cough syrups. Therefore, the syndrome has been recognized as one of the common psychiatric conditions that might develop in patients with a history of any psychoactive substance use. Recently, more attention has been paid to the biological basis of amotivational syndrome. Several studies using MRI, SPECT or neuropsychological measures have revealed white matter changes, hypoperfusion in the frontal cortex of the brain and impairment of frontal lobe function. Those findings suggest that amotivational syndrome might be related to "hypofrontality" of the brain. Although no specific treatments have been reported to be definitely effective for patients with amotivational syndrome, some neuroleptics with activating properties or antidepressants can be given appropriately to treat the chief symptoms of the patients.
Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology.

PubMed

Potter, David J; Clark, Peter; Brown, Marc B

2008-01-01

Gas chromatography was used to study the cannabinoid content ("potency") of illicit cannabis seized by police in England in 2004/5. Of the four hundred and fifty two samples, indoor-grown unpollinated female cannabis ("sinsemilla") was the most frequent form, followed by resin (hashish) and imported outdoor-grown herbal cannabis (marijuana). The content of the psychoactive cannabinoid delta 9-tetrahydrocannabinol (THC) varied widely. The median THC content of herbal cannabis and resin was 2.1% and 3.5%, respectively. The median 13.9% THC content of sinsemilla was significantly higher than that recorded in the UK in 1996/8. In sinsemilla and imported herbal cannabis, the content of the antipsychotic cannabinoid cannabidiol (CBD) was extremely low. In resin, however, the average CBD content exceeded that of THC, and the relative proportions of the two cannabinoids varied widely between samples. The increases in average THC content and relative popularity of sinsemilla cannabis, combined with the absence of the anti-psychotic cannabinoid CBD, suggest that the current trends in cannabis use pose an increasing risk to those users susceptible to the harmful psychological effects associated with high doses of THC.
Drug policy and global regulatory capitalism: the case of new psychoactive substances (NPS).

PubMed

Seddon, Toby

2014-09-01

The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism. Copyright © 2014 Elsevier B.V. All rights reserved.
Analytical Strategies to Disclose Repeated Consumption of New Psychoactive Substances by Hair Analysis.

PubMed

Rotolo, Maria C; Klein, Julia; Pacifici, Roberta; Busardo, Francesco Paolo; Pichini, Simona; Marchei, Emilia

2017-01-01

New psychoactive substances (NPS) are a heterogenic group of substances with different chemical structures and psychotropic effects. Many pharmacotoxicological laboratories performing drug testing in conventional and nonconventional biological matrices for clinical and forensic purposes do not include screening procedures for NPS in their routine protocols. This is mainly due to the continued entry in the market of newly synthesized products, the low availability of reference standards, in particular of their metabolites, the low availability of immunochemical kits, etc. Moreover, many of the new compounds are very potent, and low doses ingested will lead to low concentrations in biological matrices, especially in hair. Hair analysis has become a powerful tool for detecting chronic drug use and has become a routine technique in forensic toxicology laboratories. The aim of this study was to set up analytical strategies to identify repeated consumption of NPS by hair analysis. Although UHPLC-MS/MS may represent the elective technique in studying NPS, a combination of both GC-MS and UHPLC-MS/MS techniques is useful in creating a complete toxicological image. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue.

PubMed

Marusich, Julie A; Antonazzo, Kateland R; Blough, Bruce E; Brandt, Simon D; Kavanagh, Pierce V; Partilla, John S; Baumann, Michael H

2016-02-01

In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users. Copyright © 2015 Elsevier Ltd. All rights reserved.
The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue

PubMed Central

Marusich, Julie A.; Antonazzo, Kateland R.; Blough, Bruce E.; Brandt, Simon D.; Kavanagh, Pierce V.; Partilla, John S.; Baumann, Michael H.

2015-01-01

In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users. PMID:26362361

The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

PubMed

Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

2015-08-06

The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Ethylphenidate: availability, patterns of use, and acute effects of this novel psychoactive substance.

PubMed

Ho, James H; Bailey, George P; Archer, John R H; Dargan, Paul I; Wood, David M

2015-10-01

Ethylphenidate is a novel psychoactive substance that is an analogue of methylphenidate. This paper describes its availability, patterns of use, and acute effects. Searches of the scientific and grey literature (publicly accessible Internet resources) were undertaken, using the keywords "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and "Nopaine", to identify information on the prevalence and patterns of use, desired effects, and toxicity of ethylphenidate. An Internet snapshot survey was performed on 10 February 2015 to provide information on availability and cost of ethylphenidate. The literature search identified 1 case series of acute recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence, 1 qualitative analysis of user reports on Internet drug forums, 2 conference abstracts for surveillance studies, 1 report of two cases of ethylphenidate detected in post-mortem analyses, and 198 user reports on Internet discussion forums and social media sites. The Internet snapshot survey found 83 websites selling ethylphenidate, with purchase prices ranging from £28.20 ± 0.63 (€37.71 ± 0.85) per gram for a 500-mg amount to £2.64 ± 0.57 (€3.53 ± 0.77) per gram for 1 kg. The published cases and Internet user reports suggest the acute effects of ethylphenidate are similar to other stimulant drugs; the most common route of use was by nasal insufflation. The most common desired effects were euphoria, stimulation, and increased concentration, sociability, and energy levels; the most common unwanted effects included anxiety, palpitations, insomnia, and paranoia. This review of the scientific and grey literature has demonstrated that the acute harms associated with its use are stimulant in nature and that ethylphenidate is widely available to users over the Internet, with significant discounts for bulk purchases.
Endocannabinoid contribution to Δ9-tetrahydrocannabinol discrimination in rodents

PubMed Central

Wiley, Jenny L.; Walentiny, D. Matthew; Wright, M. Jerry; Beardsley, Patrick M.; Burston, James J.; Poklis, Justin L.; Lichtman, Aron H.; Vann, Robert E.

2014-01-01

The mechanism through which marijuana produces its psychoactive effects is Δ9- tetrahydrocannabinol (THC)-induced activation of cannabinoid CB1 receptors. These receptors are normally activated by endogenous lipids, including anandamide and 2-arachidonoyl glycerol (2-AG). A logical “first step” in determination of the role of these endocannabinoids in THC’s psychoactive effects is to investigate the degree to which pharmacologically induced increases in anandamide and/or 2-AG concentrations through exogenous administration and/or systemic administration of inhibitors of their metabolism, fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), respectively, share THC’s discriminative stimulus effects. To this end, adult male mice and rats were trained to discriminate THC (5.6 and 3 mg/kg, respectively). In Experiment 1, exogenous administration of anandamide or 2-AG did not substitute for THC in mice nor was substitution enhanced by co-administration of the FAAH or MAGL inhibitors, URB597 and N-arachidonyl maleimide (NAM), respectively. Significant decreases in responding may have prevented assessment of adequate endocannabinoid doses. In mice trained at higher baseline response rates (Experiment 2), the FAAH inhibitor PF3845 (10 mg/kg) enhanced anandamide substitution for THC without producing effects of its own. The MAGL inhibitor JZL184 increased brain levels of 2-AG in vitro and in vivo, increased THC-like responding without co-administration of 2-AG. In rats, neither URB597 nor JZL184 engendered significant THC-appropriate responding, but co-administration of these two enzyme inhibitors approached full substitution. The present results highlight the complex interplay between anandamide and 2-AG and suggest that endogenous increases of both endocannabinoids are most effective in elicitation of THC-like discriminative stimulus effects. PMID:24858366
Mountain Dew[R] or Mountain Don't?: A Pilot Investigation of Caffeine Use Parameters and Relations to Depression and Anxiety Symptoms in 5th- and 10th-Grade Students

ERIC Educational Resources Information Center

Luebbe, Aaron M.; Bell, Debora J.

2009-01-01

Background: Caffeine, the only licit psychoactive drug available to minors, may have a harmful impact on students' health and adjustment, yet little is known about its use or effects on students, especially from a developmental perspective. Caffeine use in 5th- and 10th-grade students was examined in a cross-sectional design, and relations and…
Even High Doses of Oral Cannabidiol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102–112; DOI: 10.1089/can.2015.0004

PubMed Central

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

Abstract This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses. PMID:28861499
Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102-112; DOI: 10.1089/can.2015.0004.

PubMed

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that "the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response." They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.
Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

PubMed

Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

2013-01-15

Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.
3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter

PubMed Central

Anneken, John H.; Angoa-Pérez, Mariana; Kuhn, Donald M.

2016-01-01

Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. PMID:25626880
A critical analysis of the implementation of a legal regulated market for new psychoactive substances ("legal highs") in New Zealand.

PubMed

Rychert, Marta; Wilkins, Chris

2018-05-01

In July 2013 New Zealand passed the Psychoactive Substances Act (PSA) to establish the world's first regulated legal market for new psychoactive substances (NPS) ("legal highs"). To critically analyse the implementation of the PSA. Synthesis of findings from interviews with 30 key informants (i.e. politicians, civil servants, legal high industry actors, toxicologists, NGO representatives and drug policy academics), analysis of relevant laws and policy documents, and a review of academic and grey literature on the PSA. Key challenges experienced during the implementation of the PSA included the harmfulness of interim approved products, the slowness in withdrawing products which caused adverse effects, enforcing retail restrictions, price competition by retailers, judicial challenges by the "legal high" industry, and growing opposition to the regime from local communities and key stakeholders (including local councils). The PSA lacks a tax on products and restrictions on retail opening hours which likely contributed to the problems above. The implementation of the PSA also appeared to suffer from a rushed legislative process and resource constraints on the regulatory agency which led to delays in the development of the full regulatory framework, including the product testing requirements, and issues with enforcing retail regulation, such as the minimum age of purchase. The decline in public support for the PSA regime reflected problems with communicating the aims of the policy to the general public. The troubled implementation of the PSA underlines a number of important lessons for consideration when developing a regulated legal drug market, including advanced development of regulatory systems, ensuring the sale of low risk products, adequately resourcing regulatory agencies and related enforcement activity, detailed regulation of retail outlets, establishing price controls, and ongoing engagement with stakeholders and the general public. Copyright © 2018 Elsevier B.V. All rights reserved.
The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

PubMed Central

Sanz, Camila; Zamberlan, Federico; Erowid, Earth; Erowid, Fire; Tagliazucchi, Enzo

2018-01-01

Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states) is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD), whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”), emotion (“fear”), setting (“outside,” “inside,” “street,” “front,” “behind”) and relatives (“mom,” “dad,” “brother,” “parent,” “family”) were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain physiology. PMID:29403350
A 3-year review of new psychoactive substances in casework.

PubMed

Elliott, Simon; Evans, Julie

2014-10-01

Following the initial popularity of mephedrone (4-methylmethcathinone) there has been a stream of new "recreational drugs" entering the global market. The lack of clinical studies on the effects and toxicity of these drugs has made interpretation of toxicological findings difficult. In an attempt to assist in a better understanding of the extent of their use and the fatalities that have been linked to these compounds we present our collated findings in post-mortem and criminal casework where these have been detected and/or implicated. Between January 2010 and December 2012 we have detected new psychoactive substances (NPS) in 203 cases, with 120 cases in 2012 alone. The drugs detected in in life or post-mortem blood and urine are, in order of decreasing frequency; mephedrone, 4-methylethcathinone, BZP, MDPV, TFMPP, methoxetamine, 4-fluoromethcathinone, 4-methylamphetamine, PMA, methylone, PMMA, naphyrone, alpha-methyltryptamine, butylone, MDAI, desoxypipradrol, D2PM, MPA, synthetic cannabinoids, 2-AI, 5-IAI, 5-MeODALT, MDPBP, 5/6-APB, pentedrone and pentylone. Other drugs or alcohol were detected in 84% of the cases including other NPS and in fatalities it should be noted that alternative causes of death (including mechanical suicide, accidental death and non-psychoactive drug overdose) accounted for the majority. Related to this was that of all fatalities involving cathinones, 41% of these were hangings or other mechanical suicides, this was a higher proportion than seen with other drugs found in such cases. The presence of multiple NPS and/or other stimulants was a particular feature in various cases, however, of the drug deaths only 7% solely involved NPS. Across all case types and including some cases investigated in 2013, NPS concentrations showed a wide range but these and selected cases are presented to assist toxicological interpretation in future cases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Patterns and correlates of new psychoactive substance use in a sample of Australian high school students.

PubMed

Champion, Katrina E; Teesson, Maree; Newton, Nicola C

2016-05-01

In recent years there has been growing concern about new psychoactive substances (NPS) designed to mimic the effects of established illicit drugs. This paper explores the patterns and correlates of NPS use in a sample of Australian students. A cross-sectional survey was conducted in Australia in 2014. Data were collected from 1126 students (mean age: 14.9 years) from 11 secondary schools. Students completed a self-report questionnaire assessing NPS use and knowledge, beliefs and intentions to use these substances. NPS users were compared with non-users and illicit drug users, who had not used NPS, in terms of gender, binge drinking, tobacco use, psychological distress and self-efficacy to resist peer pressure. Of the 1126 students, 3% reported having ever tried NPS, 2.4% had used synthetic cannabis and 0.4% had used a synthetic stimulant. Analyses revealed that NPS users were more likely to have had an episode of binge drinking in the past 6 months, tried tobacco and had higher levels of psychological distress and lower perceived self-efficacy to resist peer pressure than non-users, but did not significantly differ from users of other illicit drugs. NPS use appears to be uncommon among Australian school students. Although adolescents that do use these substances did not differ from students that had used traditional illicit drugs, both appear to be higher-risk groups of students than non-users. Our findings suggest that universal education about NPS be incorporated into existing drug prevention programmes, and that targeted NPS prevention may also be warranted among high-risk adolescents. [Champion KE, Teesson M, Newton NC. Patterns and correlates of new psychoactive substance use in a sample of Australian high school students. Drug Alcohol Rev 2016;35:338-344]. © 2015 Australasian Professional Society on Alcohol and other Drugs.
Decline in new psychoactive substance use disorders following legislation targeting headshops: Evidence from national addiction treatment data.

PubMed

Smyth, Bobby P; Lyons, Suzi; Cullen, Walter

2017-09-01

New psychoactive substances (NPS) have hedonic effects that may lead to dependence. Headshops selling NPS increased in number in Ireland from late 2009. Legislation was enacted in May and August of 2010 that caused their closure. It is unknown whether such events impact the rate of NPS use disorders. We conducted a population-based study using the Irish national database of episodes of addiction treatment between 2009 and 2012. We examined trends in the rate of NPS-related treatment episodes among young adults. Joinpoint trend analysis software was used to identify significant changes in trend. Of the 31 284 episodes of addiction treatment commenced by adults aged 18 to 34 years, 756 (2.4%) were NPS related. In 2012, the 12-month moving average rate had fallen 48% from its peak in 2010, from 9.0/100 000 to 4.7/100 000. Joinpoint analysis indicated that the rate of NPS related episodes increased by 218% (95% confidence interval 86 to 445, P = 0.001) every 4 months until the first third of 2010. From that point, the rate declined by 9.8% (95% confidence interval -14.1 to -5.4, P = 0.001) per 4-month period. There was no significant trend change in the rate of non-NPS related treatment episodes. Over the 2 years after the enactment of prohibition-styled legislation targeting NPS and headshops, the rate of NPS related addiction treatment episodes among young adults declined progressively and substantially. We found no coinciding trend change in the rate of episodes linked to other drug groups. [Smyth BP, Lyons S, Cullen W. Decline in new psychoactive substance use disorders following legislation targeting headshops: Evidence fromnational addiction treatment data. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.
When good times go bad: managing 'legal high' complications in the emergency department.

PubMed

Caffrey, Charles R; Lank, Patrick M

2018-01-01

Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get "legal highs." Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of "legal highs," or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka "designer drugs," but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used "legal high" substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department.
Rapid screening of 35 new psychoactive substances by ion mobility spectrometry (IMS) and direct analysis in real time (DART) coupled to quadrupole time-of-flight mass spectrometry (QTOF-MS).

PubMed

Gwak, Seongshin; Almirall, Jose R

2015-10-01

The recent propagation of new psychoactive substances (NPS) has led to the development of new techniques for the rapid characterization of controlled substances in this category. A commercial bench-top ion mobility spectrometer (IMS) with a (63) Ni ionization source and a direct analysis in real time (DART) coupled to quadrupole time-of-flight (QTOF) were used for the rapid characterization of 35 NPS. The advantages of these techniques are fast response, ease of operation, and minimal sample preparation. The characteristic reduced mobilities of each substance are reported as are the mass spectra of the 35 compounds. The acquired product ion scan mass spectra were also compared to a library database constructed by QTOF with a electrospray ionization (ESI) source and showed a consistent relative abundance for each peak over time. A total of four seized drug samples provided by the local forensic laboratory were analyzed in order to demonstrate the utility of this approach. The results of this study suggest that both IMS and DART-QTOF are promising alternatives for the rapid screening and characterization of these new psychoactive substances. Copyright © 2015 John Wiley & Sons, Ltd.
Safety reports on the off-label use of baclofen for alcohol-dependence: recommendations to improve causality assessment.

PubMed

Rolland, Benjamin; Auffret, Marine; Franchitto, Nicolas

2016-06-01

The off-label use of high-dose baclofen (HDB) for alcohol-dependence has recently spread. However, HDB has been associated with numerous reports of adverse events (AEs). Pharmacovigilance reporting is supposed to differentiate AEs from adverse drug reactions (ADRs), for which the causality of the drug is determined using validated methods. Since 2010, we found 20 publications on baclofen-related AEs in alcohol dependence, in Medline-referenced journals or national pharmacovigilance reports. We focused on whether these reports used causality algorithms, and provided essential elements for determining baclofen causality and excluding the involvement of alcohol and other psychoactive substances or psychotropic drugs. In half of the cases, no causality algorithm was used. Detailed information on baclofen dosing was found in 17 out of 20 (85%) articles, whereas alcohol doses were given only in 10 (50%) publications. Other psychoactive substances and psychotropic drugs were broached in 14 (70%) publications. future publications reporting suspected HDB-induced ADRs should use validated causality algorithms and provide sufficient amount of contextual information for excluding other potential causes. For HDB, the psychiatric history, and the longitudinal description of alcohol consumptions and associated doses of psychoactive substances or psychotropic medications should be detailed for every reported case.
[Drug-facilitated crimes: prospective data collection in a forensic unit in Paris].

PubMed

Questel, Franck; Sec, Isabelle; Sicot, Romain; Pourriat, Jean-Louis

2009-01-01

Little is known about the rate of crimes that are facilitated by the administration of psychoactive products without the victim's knowledge. This study analyzes the cases collected over a two-year period in a forensic unit in Paris. The study covers the period from January 1, 2005 and December /31, 2006. It includes crime victims who consulted for toxicological testing in the forensic unit of the Hôtel Dieu in Paris, after filing a criminal complaint describing symptoms suggestive of chemical submission (amnesia, impaired vigilance or behavior) and whose toxicological tests indicated the presence of a psychoactive product that they had not been aware of taking. The tests used chromatographic techniques on blood, urine, hair, and food or drink residue. Toxicological testing identified 52 cases of drug-facilitated crimes, primarily for theft and sexual abuse (including rape). The psychoactive products were most often incorporated in drinks, half of them alcoholic beverages. Benzodiazepines accounted for 77% of the cases. Other substances, found more rarely, included antihistamines, neuroleptics, and GHB. Appropriate samples must be taken from victims rapidly to enable toxicological analysis. Chromatographic analysis must supplement immunological analysis, which is not sufficiently specific or sensitive. The collection of this information must continue in order to quantify the phenomenon and monitor the emergence of new products.
Synthetic cannabinoids: In silico prediction of the cannabinoid receptor 1 affinity by a quantitative structure-activity relationship model.

PubMed

Paulke, Alexander; Proschak, Ewgenij; Sommer, Kai; Achenbach, Janosch; Wunder, Cora; Toennes, Stefan W

2016-03-14

The number of new synthetic psychoactive compounds increase steadily. Among the group of these psychoactive compounds, the synthetic cannabinoids (SCBs) are most popular and serve as a substitute of herbal cannabis. More than 600 of these substances already exist. For some SCBs the in vitro cannabinoid receptor 1 (CB1) affinity is known, but for the majority it is unknown. A quantitative structure-activity relationship (QSAR) model was developed, which allows the determination of the SCBs affinity to CB1 (expressed as binding constant (Ki)) without reference substances. The chemically advance template search descriptor was used for vector representation of the compound structures. The similarity between two molecules was calculated using the Feature-Pair Distribution Similarity. The Ki values were calculated using the Inverse Distance Weighting method. The prediction model was validated using a cross validation procedure. The predicted Ki values of some new SCBs were in a range between 20 (considerably higher affinity to CB1 than THC) to 468 (considerably lower affinity to CB1 than THC). The present QSAR model can serve as a simple, fast and cheap tool to get a first hint of the biological activity of new synthetic cannabinoids or of other new psychoactive compounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Preventive effects of fructose and N-acetyl-L-cysteine against cytotoxicity induced by the psychoactive compounds N-methyl-5-(2-aminopropyl)benzofuran and 3,4-methylenedioxy-N-methamphetamine in isolated rat hepatocytes.

PubMed

Nakagawa, Yoshio; Suzuki, Toshinari; Inomata, Akiko

2018-02-01

Psychoactive compounds, N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB) and 3,4-methylenedioxy-N-methamphetamine (MDMA), are known to be hepatotoxic in humans and/or experimental animals. As previous studies suggested that these compounds elicited cytotoxicity via mitochondrial dysfunction and/or oxidative stress in rat hepatocytes, the protective effects of fructose and N-acetyl-l-cysteine (NAC) on 5-MAPB- and MDMA-induced toxicity were studied in rat hepatocytes. These drugs caused not only concentration-dependent (0-4 mm) and time-dependent (0-3 hours) cell death accompanied by the depletion of cellular levels of adenosine triphosphate (ATP) and glutathione (reduced form; GSH) but also an increase in the oxidized form of GSH. The toxic effects of 5-MAPB were greater than those of MDMA. Pretreatment of hepatocytes with either fructose at a concentration of 10 mm or NAC at a concentration of 2.5 mm prevented 5-MAPB-/MDMA-induced cytotoxicity. In addition, the exposure of hepatocytes to 5-MAPB/MDMA caused the loss of mitochondrial membrane potential, although the preventive effect of fructose was weaker than that of NAC. These results suggest that: (1) 5-MAPB-/MDMA-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were ameliorated, at least in part, by the addition of fructose; and (3) GSH loss via oxidative stress was prevented by NAC. Taken collectively, these results indicate that the onset of toxic effects caused by 5-MAPB/MDMA may be partially attributable to cellular energy stress as well as oxidative stress. Copyright © 2017 John Wiley & Sons, Ltd.
Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain

PubMed Central

Moussaieff, Arieh; Rimmerman, Neta; Bregman, Tatiana; Straiker, Alex; Felder, Christian C.; Shoham, Shai; Kashman, Yoel; Huang, Susan M.; Lee, Hyosang; Shohami, Esther; Mackie, Ken; Caterina, Michael J.; Walker, J. Michael; Fride, Ester; Mechoulam, Raphael

2008-01-01

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3−/− mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3−/− mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. PMID:18492727

Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential

PubMed Central

Tai, Sherrica; Fantegrossi, William E.

2015-01-01

Cannabis has been used throughout the world for centuries. The psychoactive effects of cannabis are largely attributable to Δ9-tetrahydrocannabinol (Δ9-THC), the prototypical cannabinoid that occurs naturally in the plant. More recently, chemically- and pharmacologically-distinct synthetic cannabinoids (SCBs) have emerged as drugs of abuse. As compared to Δ9-THC, the distinct structures of these compounds allow them to avoid legal restrictions (at least initially) and detection in standard drug screens. This has contributed to the popularity of SCBs among drug users who seek to avoid positive drug screens. Importantly, the distinct structures of the SCBs also typically result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be responsible for the psychoactive effects of Δ9-THC and its analogues. Accordingly, it seems likely that these more powerful cannabimimetic effects could result in increased adverse reactions and toxicities not elicited by Δ9-THC in cannabis. Animal models useful for the study of emerging SCBs include the cannabinoid tetrad, drug discrimination, and assays of tolerance, dependence, and withdrawal. However, these in vivo procedures have not been particularly informative with regards to drug efficacy, where the majority of SCB effects are comparable to those of Δ9-THC. In contrast, essentially all in vitro measures of drug efficacy confirm Δ9-THC as a relatively weak CB1 partial agonist, while the majority of the SCBs detected in commercial preparations are full agonists at the CB1 receptor. As use of these emerging SCBs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds. PMID:26413452
Presentations due to acute toxicity of psychoactive substances in an urban emergency department in Switzerland: a case series.

PubMed

Liakoni, Evangelia; Dolder, Patrick C; Rentsch, Katharina M; Liechti, Matthias E

2016-05-26

Although the recreational use of psychoactive substances is common there is only limited systematic collection of data on acute drug toxicity or hospital presentations, in particular regarding novel psychoactive substances (NPS) that have emerged on the illicit market in the last years. We included all cases presenting at the emergency department (ED) of the University Hospital of Basel, Switzerland, between October 2014 and September 2015 with acute toxicity due to self-reported recreational drug use or with symptoms/signs consistent with acute toxicity. Intoxications were confirmed using immunoassays and LC-MS/MS, detecting also novel psychoactive substances. Among the 50'624 attendances at the ED, 210 were directly related to acute toxicity of recreational drugs. The mean patient age was 33 years and 73 % were male. Analytical drug confirmation was available in 136 cases. Most presentations were reportedly related to cocaine (33 %), cannabis (32 %), and heroin (14 %). The most commonly analytically detected substances were cannabis (33 %), cocaine (27 %), and opioids excluding methadone (19 %). There were only two NPS cases; a severe intoxication with paramethoxymethamphetamine (PMMA) in combination with other substances and an intoxication of minor severity with 2,5-dimethoxy-4-propylphenethylamine (2C-P). The most frequent symptoms were tachycardia (28 %), anxiety (23 %), nausea or vomiting (18 %), and agitation (17 %). Severe complications included two fatalities, two acute myocardial infarctions, seizures (13 cases), and psychosis (six cases). Most patients (76 %) were discharged home, 10 % were admitted to intensive care, and 2 % were referred to psychiatric care. Most medical problems related to illicit drugs concerned cocaine and cannabis and mainly included sympathomimetic toxicity and/or psychiatric disorders confirming data from the prior year. Importantly, despite the dramatic increase in various NPS being detected in the last years, these substances were infrequently associated with ED presentations compared with classic recreational drugs.
Prevalence of psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A roadside study in 2015.

PubMed

Domingo-Salvany, Antonia; Herrero, M Jesús; Fernandez, Beatriz; Perez, Julio; Del Real, Pilar; González-Luque, Juan Carlos; de la Torre, Rafael

2017-09-01

A survey was conducted during 2015 to monitor psychoactive substance use in a sample of drivers in Spanish roads and cities. Traffic police officers recruited drivers at sites carefully chosen to achieve representativeness of the driver population. A brief questionnaire included the date, time, and personal and driving patterns data. Alcohol use was ascertained through ethanol breath test at the roadside and considered positive if concentrations >0.05mg alcohol/L were detected. Four drug classes were assessed on-site through an oral fluid screening test that, if positive, was confirmed through a second oral fluid sample at a reference laboratory. Laboratory confirmation analyses screened for 26 psychoactive substances. To evaluate the association between drug findings and age, sex, road type (urban/interurban), and period of the week (weekdays, weeknights, weekend days, weekend nights), logistic regression analyses were done (overall, and separately for alcohol, cannabis and cocaine). A total of 2744 drivers, mean age of 37.5 years, 77.8% men, were included. Overall, 11.6% of the drivers had at least one positive finding to the substances assessed. Substances more frequently testing positive were cannabis (7.5%), cocaine (4.7%) and alcohol (2.6%). More than one substance was detected in 4% of the subjects. The proportion of positive results decreased with age, and was more likely among men and on urban roads. The pattern for alcohol use was similar but did not change with age and increased among drivers recruited at night. Cannabis was more likely to be detected at younger ages and cocaine was associated with night driving. Alcohol use before driving has decreased over the last decade; however, the consumption of other illegal drugs seems to have increased. The pattern of illegal psychoactive substance observed is similar to that declared in surveys of the general population of adults. Copyright © 2017. Published by Elsevier B.V.
An Internet snapshot study to compare the international availability of the novel psychoactive substance methiopropamine.

PubMed

Vermette-Marcotte, A-E; Dargan, P I; Archer, J R H; Gosselin, S; Wood, D M

2014-08-01

With the increased use of novel psychoactive substances, there is an increasing availability of these substances from Internet-based suppliers. Methiopropamine, first reported in 2011, is a recreational drug available over the Internet. The aim of this study was to investigate availability and cost of methiopropamine in three different countries: the UK, France, and Canada. Using the European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, this study, conducted in June 2013, was undertaken in two different languages: in English (the UK and Canada) and in French (France and Canada), using three Internet searching engines: " google.co.uk ", " google.fr " and " google.ca ". A total of 62 sites were found, most of them were found from the English searches. 45% of the suppliers seemed to originate from the UK. The prices of methiopropamine were comparable between suppliers, no matter which search engine or language was used. The cost of a unit of methiopropamine was inversely related to the purchased quantity, going from 19.49 ± 0.15 GBP per gram for a purchase amount of 500 mg to 3.54 ± 0.13 GBP per gram for a purchase amount of 1 kg. The results of the present study demonstrate that the sale of methiopropamine has the potential to reach users across the world. It also appears to support that snapshot studies could be used for toxicovigilance across different countries, by studying the Internet market of novel psychoactive substances. To date, snapshot studies, used to monitor the Internet novel psychoactive substances market, have only been undertaken in Europe. We have shown that the flexibility of this methodology enables comparison of the online activity of drug sellers between different countries and continents and that, at least for methiopropamine, the UK is the predominant source for Internet supply.
[Recreational usage of dextromethorphan--analysis based on internet users experiences].

PubMed

Zajac, Maciej; Andrzejczyk, Agata; Kuich, Aleksandra; Tyrańska-Fobke, Anna; Waldman, Wojciech; Sein Anand, Jacek

2013-01-01

In the last decade we have observed a considerable increase in nonmedical usage of dextromethorphan (DXM) among young age groups, especially school children between 13 and 16 yrs. We analysed the "trip reports" after use of DXM, available on a website: www.hyperreal.info in the years 1999-2013. The data collected by authors were analysed according to: age, sex, symptoms, dose of DXM, a reason and a place of using the drug. A review of 124 "trip reports" showed that the majority of their writers are male (M 90.3%, F 9.7%). Young people, aged 16-20 (80.4%), dominated among the study population. The most common place of using DXM was a flat of a drug user (70.2%), and the reason of using a willingness to experiment with new psychoactive substances (41.9%) as well as the desire of "get high" (25.8%). The majority of users used DXM at least once again in their lives (56.5%). A single dose of the ingested drug ranged from 120 mg to 1575 mg (mean 539.25 mg). Most often received doses were 450 mg (30.4%), 300 mg (12%), 900 mg (11.2%). DXM was positively assessed by the internauts as a recreational psychoactive substance (84.7%). The most common clinical symptoms described by internauts were: difficulties with walking (74.2%), visual illusions (73.4%), altered sense of time (41.9%), feeling of exteriorisation (35.5%), euphoria (33.1%), nausea and vomiting (32.3%), auditory illusions (30.6%) and pruritus (29.8%). 1. DXM is the popular psychoactive substance which has gained a positive opinion among the Internet users. 2. Easy accessibility of DXM may pose a serious threat to health of young people who experiment with psychoactive substances. 3. The improvement of DXM sales control should be considered.
Understanding the development of a regulated market approach to new psychoactive substances (NPS) in New Zealand using Punctuated Equilibrium Theory.

PubMed

Rychert, Marta; Wilkins, Chris

2018-05-09

The short-lived regulated legal market for new psychoactive substances (NPS) in New Zealand marked a radical departure from the traditional prohibition-based approach to drugs. This paper aimed to enhance understanding of this policy change using Punctuated Equilibrium Theory (PET). The analysis draws on 3 years of evaluative research, including interviews with key stakeholders, analysis of legislation and policy documents and academic and grey literature. The reframing of the NPS issue from one of drug control to the need for stricter market regulation was achieved by the efforts of strategic policy entrepreneurs, including the legal high industry, drug law reform advocates, influential politicians and an independent legal advisory institution. This reframing was aided by the perceived saliency of the NPS problem and ineffectiveness of previous prohibition-based responses. In the absence of any political opposition to the regulatory approach, the Psychoactive Substances Act rapidly progressed through the Parliament. However, once the interim legal market was established, portrayal of the issues shifted away from experts and lobbyists to critique from local communities, local government, animal rights activists and the media, who viewed the new regime as a source of social and health problems. The mobilization of criticism ('Schattschneider mobilization') drew on ideas of animal welfare and community safety. With a looming national election, the government responded by ending the interim market with the urgent passage of amendment legislation. Punctuated Equilibrium Theory (PET) helps explain how New Zealand's Psychoactive Substances Act (PSA) policy first emerged on the political agenda and how the initial positive tone of expert support for reform shifted to a tide of popular criticism during the interim regime. However, with its emphasis on explaining agenda-setting, PET does not account for the legislative design shortcomings of the PSA. © 2018 Society for the Study of Addiction.
Toxoplasma gondii exposure in patients suffering from mental and behavioral disorders due to psychoactive substance use.

PubMed

Alvarado-Esquivel, Cosme; Carrillo-Oropeza, David; Pacheco-Vega, Sandy Janet; Hernández-Tinoco, Jesús; Salcedo-Jaquez, Misael; Sánchez-Anguiano, Luis Francisco; Ortiz-Jurado, María Nalleli; Alarcón-Alvarado, Yesenia; Liesenfeld, Oliver; Beristain-García, Isabel

2015-04-03

Toxoplasma gondii infection has been associated with psychiatric diseases. However, there is no information about the link between this infection and patients with mental and behavioral disorders due to psychoactive substance use. We performed a case-control study with 149 psychiatric patients suffering from mental and behavioral disorders due to psychoactive substance use and 149 age- and gender-matched control subjects of the general population. We searched for anti-T. gondii IgG and IgM antibodies in the sera of participants by means of commercially available enzyme-linked immunoassays. Seroprevalence association with socio-demographic, clinical and behavioral characteristics in psychiatric patients was also investigated. Anti-T. gondii IgG antibodies were present in 15 (10.1%) of 149 cases and in 14 (9.4%) of 149 controls (P=1.0). Anti-T. gondii IgM antibodies were found in 11 (7.4%) of the 149 cases and in 16 (10.7%) of the 149 controls (P=0.31). No association of T. gondii exposure with socio-demographic characteristics of patients was found. Multivariate analysis of clinical and behavioral characteristics of cases showed that T. gondii seropositivity was positively associated with consumption of opossum meat (OR=10.78; 95% CI: 2.16-53.81; P=0.003) and soil flooring at home (OR=11.15; 95% CI: 1.58-78.92; P=0.01), and negatively associated with suicidal ideation (OR=0.17; 95% CI: 0.05-0.64; P=0.008). Mental and behavioral disorders due to psychoactive substance use do not appear to represent an increased risk for T. gondii exposure. This is the first report of a positive association of T. gondii exposure with consumption of opossum meat. Further studies to elucidate the role of T. gondii infection in suicidal ideation and behavior are needed to develop optimal strategies for the prevention of infection with T. gondii.
Psychiatric diagnoses and psychoactive medication use among nonsurgical critically ill patients receiving mechanical ventilation.

PubMed

Wunsch, Hannah; Christiansen, Christian F; Johansen, Martin B; Olsen, Morten; Ali, Naeem; Angus, Derek C; Sørensen, Henrik Toft

2014-03-19

The relationship between critical illness and psychiatric illness is unclear. To assess psychiatric diagnoses and medication prescriptions before and after critical illness. Population-based cohort study in Denmark of critically ill patients in 2006-2008 with follow-up through 2009, and 2 matched comparison cohorts from hospitalized patients and from the general population. Critical illness defined as intensive care unit admission with mechanical ventilation. Adjusted prevalence ratios (PRs) of psychiatrist-diagnosed psychiatric illnesses and prescriptions for psychoactive medications in the 5 years before critical illness. For patients with no psychiatric history, quarterly cumulative incidence (risk) and adjusted hazard ratios (HRs) for diagnoses and medications in the following year, using Cox regression. Among 24,179 critically ill patients, 6.2% had 1 or more psychiatric diagnoses in the prior 5 years vs 5.4% for hospitalized patients (adjusted PR, 1.31; 95% CI, 1.22-1.42; P<.001) and 2.4% for the general population (adjusted PR, 2.57; 95% CI, 2.41-2.73; P<.001). Five-year preadmission psychoactive prescription rates were similar to hospitalized patients: 48.7% vs 48.8% (adjusted PR, 0.97; 95% CI, 0.95-0.99; P<.001) but were higher than the general population (33.2%; adjusted PR, 1.40; 95% CI, 1.38-1.42; P<.001). Among the 9912 critical illness survivors with no psychiatric history, the absolute risk of new psychiatric diagnoses was low but higher than hospitalized patients: 0.5% vs 0.2% over the first 3 months (adjusted HR, 3.42; 95% CI, 1.96-5.99; P <.001), and the general population cohort (0.02%; adjusted HR, 21.77; 95% CI, 9.23-51.36; P<.001). Risk of new psychoactive medication prescriptions was also increased in the first 3 months: 12.7% vs 5.0% for the hospital cohort (adjusted HR, 2.45; 95% CI, 2.19-2.74; P<.001) and 0.7% for the general population (adjusted HR, 21.09; 95% CI, 17.92-24.82; P<.001). These differences had largely resolved by 9 to 12 months after discharge. Prior psychiatric diagnoses are more common in critically ill patients than in hospital and general population cohorts. Among survivors of critical illness, new psychiatric diagnoses and psychoactive medication use is increased in the months after discharge. Our data suggest both a possible role of psychiatric disease in predisposing patients to critical illness and an increased but transient risk of new psychiatric diagnoses and treatment after critical illness.
[Legal, illegal and legitimate in the use and misuse of substances].

PubMed

Ghioldi, Leonardo

2016-11-01

his article attempts to establish a dialogue between existing laws, their effectiveness and the controversy within the context of the popularization of substance use in the country. To this end, the origin of the criminalization of substance use and the contradictory positions that have been adopted in laws and court rulings are tracked. All this is confronted with the growing habit of psychoactive substance use among general population, which no laws and rulings have yet managed to in?uence.
Psychoactive drug advertising: content analysis.

PubMed

Mastroianni, Patrícia C; Vaz, Amanda Cristina R; Noto, Ana Regina; Galduróz, José Carlos F

2008-10-01

The goal of this study was to describe the human figures portrayed in psychoactive drug advertising in terms of gender, age, ethnic group, and social context. Content analysis for 86 new pieces of printed advertisements released in 2005 was carried out. Fisher exact test was used to analyze the association between categories. There was a preponderance of women (62.8%) who were four times more present in advertisements for antidepressants and anxyolitics than men. Most of the people shown were Caucasian (98.8%) young adults (72%). These people were pictured in leisure activities (46.5%), at home (29%), or in contact with nature (16.2%). The message conveyed was that the drugs treat routinely felt subjective symptoms of discomfort, inducing in an irrational appeal that may affect drug prescription.
[Plants' materials and synthetic agonists of cannabinoid receptors use as a substitute of Marihuana, appearing in a current forensic toxicology practice of evidence materials].

PubMed

Geppert, Bogna; Tezyk, Artur; Florek, Ewa; Zaba, Czesław

2010-01-01

Cannabis sativa species Indica (Marihuana) is nowadays one of the most common plant drug, with psychoactive activity, presently appearing on the illegal market in Poland. It is reported that frequency of securing evidential materials so called substitute of Marihuana, is growing rapidly during the last few years. The substitutes of Marihuana occurring on the market are of natural or synthetic origins, for example different species of raw plants' materials having action similar to Cannabis or raw plants' materials with no psychoactive properities but with an addition of components so called synthetic cannabinoids. The review presents recent developments in drug market and current problems of forensic toxicology on the example of Marihuana.
Brephedrone: A new psychoactive substance seized in Brazil.

PubMed

Machado, Yuri; Coelho Neto, José; Barbosa, Paulo Eduardo Nunes; Lordeiro, Rogério Araújo; Alves, Rosemeire Brondi

2017-06-01

At the beginning of 2015, sixty-two capsules containing red-brown crystals seized in a historical city in Brazil were sent to this forensic laboratory for drug testing analysis. The material was identified as being Brephedrone, a new psychoactive substance and a bromine synthetic cathinone that is related to serotonin transportation. This substance was analyzed by ATR-FTIR, GC-MS, LC-MS, 1 H, 13 C and 2D NMR. Brephedrone apprehensions have been previously reported in Finland, France and Spain. It was the first detection of this substance in the State of Minas Gerais. No reports or information regarding any other apprehension nor identification of Brephedrone in Brazil were known prior to the present case. Copyright © 2017 Elsevier B.V. All rights reserved.
Recent developments in urinalysis of metabolites of new psychoactive substances using LC-MS.

PubMed

Peters, Frank T

2014-08-01

In the last decade, an ever-increasing number of new psychoactive substances (NPSs) have appeared on the recreational drug market. To account for this development, analytical toxicologists have to continuously adapt their methods to encompass the latest NPSs. Urine is the preferred biological matrix for screening analysis in different areas of analytical toxicology. However, the development of urinalysis procedures for NPSs is complicated by the fact that generally little or no information on urinary excretion patterns of such drugs exists when they first appear on the market. Metabolism studies are therefore a prerequisite in the development of urinalysis methods for NPSs. In this article, the literature on the urinalysis of NPS metabolites will be reviewed, focusing on articles published after 2008.
Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.

PubMed

Kogan, Natalya M; Melamed, Eitan; Wasserman, Elad; Raphael, Bitya; Breuer, Aviva; Stok, Kathryn S; Sondergaard, Rachel; Escudero, Ana V Villarreal; Baraghithy, Saja; Attar-Namdar, Malka; Friedlander-Barenboim, Silvina; Mathavan, Neashan; Isaksson, Hanna; Mechoulam, Raphael; Müller, Ralph; Bajayo, Alon; Gabet, Yankel; Bab, Itai

2015-10-01

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.
Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs.

PubMed

Thaler, David S

2009-06-16

A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702-705) offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem.Whatever the fate of these specific hypotheses, discussion of cognitive enhancing drugs for healthy individuals has the potential to inspire innovative educational and public policy initiatives toward all types of mind-altering drugs and the people who use them.
(+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burris, K.D.; Breeding, M.; Sanders-Bush, E.

Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation.more » (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.« less
5-(2-Aminopropyl)indole (5-IT): a psychoactive substance used for recreational purposes is an inhibitor of human monoamine oxidase (MAO).

PubMed

Herraiz, Tomás; Brandt, Simon D

2014-01-01

5-(2-Aminopropyl)indole (5-IT) is a psychoactive compound that has recently been associated with several fatal and non-fatal intoxications in a number of European countries. There are indications that acute effects may include symptoms of monoaminergic (e.g. serotonin) toxicity and one mechanism involved in the increase of serotonin levels includes the inhibition of monoamine oxidase. This study investigated the effect of 5-IT on human MAO-A and -B isozymes using kynuramine as the substrate. Substrate conversion to 4-hydroxyquinoline was monitored by high-performance liquid chromatography coupled to diode array detection. This method was employed to determine the extent of MAO inhibition (IC50 and Ki ) and it was found that 5-IT was a selective, competitive and reversible inhibitor of MAO-A. 5-IT revealed a relatively potent ability to inhibit MAO-A (IC50 =1.6 μM and Ki =0.25 μM) while MAO-B inhibition was not observed (0-500 μM 5-IT). Under identical experimental conditions, other established inhibitors of MAO-A and antidepressants provided the following IC50 values: clorgyline 16 nM, harmaline 20 nM, toloxatone 6.7 μM and moclobemide >500 μM. These data indicated that 5-IT was less potent than clorgyline and harmaline but more potent than toloxatone and moclobemide under the in-vitro conditions studied. The inhibition of MAO-A suggests that 5-IT by itself or in combination with other substances may be able to potentiate serotonergic/monoaminergic effects and further studies are needed to clarify its relevance to the adverse effects reported for 5-IT. Copyright © 2013 John Wiley & Sons, Ltd.
Is immunotherapy an opportunity for effective treatment of drug addiction?

PubMed

Zalewska-Kaszubska, Jadwiga

2015-11-27

Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family.

PubMed

Mayer, Felix P; Burchardt, Nadine V; Decker, Ann M; Partilla, John S; Li, Yang; McLaughlin, Gavin; Kavanagh, Pierce V; Sandtner, Walter; Blough, Bruce E; Brandt, Simon D; Baumann, Michael H; Sitte, Harald H

2018-05-15

A variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide. NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. Chemical modifications of existing drugs can generate NPS that are not controlled by current legislation, thereby providing legal alternatives to controlled substances such as cocaine or amphetamine. Recently, 3-fluorophenmetrazine (3-FPM), a derivative of the anorectic compound phenmetrazine, appeared on the recreational drug market and adverse clinical effects have been reported. Phenmetrazine is known to elevate extracellular monoamine concentrations by an amphetamine-like mechanism. Here we tested 3-FPM and its positional isomers, 2-FPM and 4-FPM, for their abilities to interact with plasma membrane monoamine transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). We found that 2-, 3- and 4-FPM inhibit uptake mediated by DAT and NET in HEK293 cells with potencies comparable to cocaine (IC 50 values < 2.5 μM), but display less potent effects at SERT (IC 50 values >80 μM). Experiments directed at identifying transporter-mediated reverse transport revealed that FPM isomers induce efflux via DAT, NET and SERT in HEK293 cells, and this effect is augmented by the Na + /H + ionophore monensin. Each FPM evoked concentration-dependent release of monoamines from rat brain synaptosomes. Hence, this study reports for the first time the mode of action for 2-, 3- and 4-FPM and identifies these NPS as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addiction. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult brain and behaviour: Variants of learning, anxiety and volumetric estimates.

PubMed

Keeley, R J; Trow, J; Bye, C; McDonald, R J

2015-07-15

Marijuana is one of the most highly used psychoactive substances in the world, and its use typically begins during adolescence, a period of substantial brain development. Females across species appear to be more susceptible to the long-term consequences of marijuana use. Despite the identification of inherent differences between rat strains including measures of anatomy, genetics and behaviour, no studies to our knowledge have examined the long-term consequences of adolescent exposure to marijuana or its main psychoactive component, Δ(9)-tetrahydrocannabinol (THC), in males and females of two widely used rat strains: Long-Evans hooded (LER) and Wistar (WR) rats. THC was administered for 14 consecutive days following puberty onset, and once they reached adulthood, changes in behaviour and in the volume of associated brain areas were quantified. Rats were assessed in behavioural tests of motor, spatial and contextual learning, and anxiety. Some tasks showed effects of injection, since handled and vehicle groups were included as controls. Performance on all tasks, except motor learning, and the volume of associated brain areas were altered with injection or THC administration, although these effects varied by strain and sex group. Finally, analysis revealed treatment-specific correlations between performance and brain volumes. This study is the first of its kind to directly compare males and females of two rat strains for the long-term consequences of adolescent THC exposure. It highlights the importance of considering strain and identifies certain rat strains as susceptible or resilient to the effects of THC. Copyright © 2015 Elsevier B.V. All rights reserved.

The Utilization of Robotic Pets in Dementia Care.

PubMed

Petersen, Sandra; Houston, Susan; Qin, Huanying; Tague, Corey; Studley, Jill

2017-01-01

Behavioral problems may affect individuals with dementia, increasing the cost and burden of care. Pet therapy has been known to be emotionally beneficial for many years. Robotic pets have been shown to have similar positive effects without the negative aspects of traditional pets. Robotic pet therapy offers an alternative to traditional pet therapy. The study rigorously assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback device, in treating dementia-related symptoms. A randomized block design with repeated measurements guided the study. Before and after measures included reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and GSR. Participants interacted with the PARO robotic pet, and the control group received standard activity programs. Five urban secure dementia units comprised the setting. 61 patients, with 77% females, average 83.4 years in age, were randomized into control and treatment groups. Compared to the control group, RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while pulse rate, pain medication, and psychoactive medication use were decreased. The changes in GSR, pulse oximetry, and pulse rate over time were plotted for both groups. The difference between groups was consistent throughout the 12-week study for pulse oximetry and pulse rate, while GSR had several weeks when changes were similar between groups. Treatment with the PARO robot decreased stress and anxiety in the treatment group and resulted in reductions in the use of psychoactive medications and pain medications in elderly clients with dementia.
The Utilization of Robotic Pets in Dementia Care

PubMed Central

Petersen, Sandra; Houston, Susan; Qin, Huanying; Tague, Corey; Studley, Jill

2016-01-01

Background: Behavioral problems may affect individuals with dementia, increasing the cost and burden of care. Pet therapy has been known to be emotionally beneficial for many years. Robotic pets have been shown to have similar positive effects without the negative aspects of traditional pets. Robotic pet therapy offers an alternative to traditional pet therapy. Objective: The study rigorously assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback device, in treating dementia-related symptoms. Methods: A randomized block design with repeated measurements guided the study. Before and after measures included reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and GSR. Participants interacted with the PARO robotic pet, and the control group received standard activity programs. Five urban secure dementia units comprised the setting. Results: 61 patients, with 77% females, average 83.4 years in age, were randomized into control and treatment groups. Compared to the control group, RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while pulse rate, pain medication, and psychoactive medication use were decreased. The changes in GSR, pulse oximetry, and pulse rate over time were plotted for both groups. The difference between groups was consistent throughout the 12-week study for pulse oximetry and pulse rate, while GSR had several weeks when changes were similar between groups. Conclusions: Treatment with the PARO robot decreased stress and anxiety in the treatment group and resulted in reductions in the use of psychoactive medications and pain medications in elderly clients with dementia. PMID:27716673
Acute Toxicity Associated With the Recreational Use of the Novel Psychoactive Benzofuran N-methyl-5-(2 aminopropyl)benzofuran.

PubMed

Hofer, Katharina E; Faber, Katrin; Müller, Daniel M; Hauffe, Till; Wenger, Urs; Kupferschmidt, Hugo; Rauber-Lüthy, Christine

2017-01-01

N-methyl-5-(2 aminopropyl)benzofuran (5-MAPB) is a novel psychoactive benzofuran, created by N-methylation of 5-(2-aminopropyl)benzofuran (5-APB), which shares structural features with methylenedioxymethamphetamine (MDMA). To our knowledge, no case of 5-MAPB-related toxicity has been published in the scientific literature. We report a case of oral 5-MAPB exposure confirmed by liquid chromatography-tandem mass spectrometry in a 24-year-old previously healthy white man. Observed symptoms and signs such as paleness, cold and clammy skin, hypertension, elevated high-sensitive troponin T level, tachycardia, ECG change, diaphoresis, mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, hallucinations, convulsions, reduced level of consciousness, and creatine kinase level elevation (305 IU/L) were compatible with undesired effects related to 5-APB or MDMA exposure. Signs and symptoms resolved substantially within 14 hours with aggressive symptomatic treatment, including sedation with benzodiazepines, external cooling, analgesia and sedation with fentanyl-propofol, and treatment with urapidil, an α-receptor-blocking agent. 5-MAPB showed first-order elimination kinetics with a half-life of 6.5 hours, comparable to the half-life of MDMA. According to the chemical structure, this case report, and users' Web reports, 5-MAPB appears to have an acute toxicity profile similar to that of 5-APB and MDMA, with marked vasoconstrictor effect. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay.

PubMed

Zwartsen, Anne; Verboven, Anouk H A; van Kleef, Regina G D M; Wijnolts, Fiona M J; Westerink, Remco H S; Hondebrink, Laura

2017-12-01

The prevalence and use of new psychoactive substances (NPS) is increasing and currently over 600 NPS exist. Many illicit drugs and NPS increase brain monoamine levels by inhibition and/or reversal of monoamine reuptake transporters (DAT, NET and SERT). This is often investigated using labor-intensive, radiometric endpoint measurements. We investigated the applicability of a novel and innovative assay that is based on a fluorescent monoamine mimicking substrate. DAT, NET or SERT-expressing human embryonic kidney (HEK293) cells were exposed to common drugs (cocaine, dl-amphetamine or MDMA), NPS (4-fluoroamphetamine, PMMA, α-PVP, 5-APB, 2C-B, 25B-NBOMe, 25I-NBOMe or methoxetamine) or the antidepressant fluoxetine. We demonstrate that this fluorescent microplate reader-based assay detects inhibition of different transporters by various drugs and discriminates between drugs. Most IC 50 values were in line with previous results from radiometric assays and within estimated human brain concentrations. However, phenethylamines showed higher IC 50 values on hSERT, possibly due to experimental differences. Compared to radiometric assays, this high-throughput fluorescent assay is uncomplicated, can measure at physiological conditions, requires no specific facilities and allows for kinetic measurements, enabling detection of transient effects. This assay is therefore a good alternative for radiometric assays to investigate effects of illicit drugs and NPS on monoamine reuptake transporters. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Synthetic Cathinones: A New Public Health Problem

PubMed Central

Karila, Laurent; Megarbane, Bruno; Cottencin, Olivier; Lejoyeux, Michel

2015-01-01

New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: “new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”, “4-MEC”, “addiction”, and “substance use disorder”. PMID:26074740
Sewage-based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC-MS/MS.

PubMed

Kinyua, Juliet; Covaci, Adrian; Maho, Walid; McCall, Ann-Kathrin; Neels, Hugo; van Nuijs, Alexander L N

2015-09-01

Sewage-based epidemiology (SBE) employs the analysis of sewage to detect and quantify drug use within a community. While SBE has been applied repeatedly for the estimation of classical illicit drugs, only few studies investigated new psychoactive substances (NPS). These compounds mimic effects of illicit drugs by introducing slight modifications to chemical structures of controlled illicit drugs. We describe the optimization, validation, and application of an analytical method using liquid chromatography coupled to positive electrospray tandem mass spectrometry (LC-ESI-MS/MS) for the determination of seven NPS in sewage: methoxetamine (MXE), butylone, ethylone, methylone, methiopropamine (MPA), 4-methoxymethamphetamine (PMMA), and 4-methoxyamphetamine (PMA). Sample preparation was performed using solid-phase extraction (SPE) with Oasis MCX cartridges. The LC separation was done with a HILIC (150 x 3 mm, 5 µm) column which ensured good resolution of the analytes with a total run time of 19 min. The lower limit of quantification (LLOQ) was between 0.5 and 5 ng/L for all compounds. The method was validated by evaluating the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recoveries and matrix effects. The method was applied on sewage samples collected from sewage treatment plants in Belgium and Switzerland in which all investigated compounds were detected, except MPA and PMA. Furthermore, a consistent presence of MXE has been observed in most of the sewage samples at levels higher than LLOQ. Copyright © 2015 John Wiley & Sons, Ltd.
The impact of the prohibition of benzylpiperazine (BZP) 'legal highs' on the prevalence of BZP, new legal highs and other drug use in New Zealand.

PubMed

Wilkins, Chris; Sweetsur, Paul

2013-01-01

Benzylpiperazine (BZP) is the psychoactive ingredient in a range of 'legal highs' sold worldwide. BZP was prohibited in New Zealand in 2008. To investigate the impact of the prohibition of BZP legal highs on the prevalence of BZP, replacement legal highs and other drugs. A population survey of BZP and other drugs was conducted in 2006 (while BZP was legal) and repeated in 2009 (+12 months after BZP was prohibited). Respondents were asked to provide the reason(s) why they had stopped using BZP. Annual surveys of frequent drug users were conducted from 2006 to 2010. Last year prevalence of BZP among the general population fell from 15.3% in 2006 to 3.2% in 2009. The most common reasons for stopping BZP use in 2008 were 'it's illegal now' (43%), 'just experimenting' (26%), 'don't know where to get it now it's illegal' (24%) and 'bad hangover effect' (18%). Three per cent of the general population had used any new legal high in 2009. Use of BZP declined among frequent methamphetamine users from 32% in 2006 to 7% in 2010; among frequent ecstasy users from 65% in 2006 to 11% in 2010; and among frequent injecting drug users from 30% in 2007 to 20% in 2010. The use of new legal highs in 2010 was lower than the former use of BZP in 2006. Unpleasant side-effects and the prohibition contributed to a decline in BZP use. The overall level of legal high use was lower following the prohibition of BZP. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA.

PubMed

Gamage, Thomas F; Farquhar, Charlotte E; Lefever, Timothy W; Marusich, Julie A; Kevin, Richard C; McGregor, Iain S; Wiley, Jenny L; Thomas, Brian F

2018-05-01

Synthetic cannabinoids are a class of novel psychoactive substances that exhibit high affinity at the cannabinoid type-1 (CB 1 ) receptor and produce effects similar to those of Δ-9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Illicit drug manufacturers are continually circumventing laws banning the sale of synthetic cannabinoids by synthesizing novel structures and doing so with little regard for the potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects that include cardiotoxicity, seizure activity, and kidney damage, and they can cause death. Six synthetic cannabinoids, recently detected in illicit preparations, MMB-FUBINACA, MDMB-FUBINACA, CUMYL-PICA, 5F-CUMYL-PICA, NNEI, and MN-18 were assessed for: 1) receptor binding affinity at the human CB 1 and human CB 2 receptors, 2) function in [ 35 S]GTP γ S and cAMP signaling, and 3) THC-like effects in a mouse drug discrimination assay. All six synthetic cannabinoids exhibited high affinity for human cannabinoid receptors type-1 and type-2 and produced greater maximal effects than THC in [ 35 S]GTP γ S and cAMP signaling. Additionally, all six synthetic cannabinoids substituted for THC in drug discrimination, suggesting they probably possess subjective effects similar to those of cannabis. Notably, MDMB-FUBINACA, a methylated analog of MMB-FUBINACA, had higher affinity for CB 1 than the parent, showing that minor structural modifications being introduced can have a large impact on the pharmacological properties of these drugs. This study demonstrates that novel structures being sold and used illicitly as substitutes for cannabis are retaining high affinity at the CB 1 receptor, exhibiting greater efficacy than THC, and producing THC-like effects in models relevant to subjective effects in humans. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.
Health effects of exposure to second- and third-hand marijuana smoke: a systematic review

PubMed Central

Holitzki, Hannah; Dowsett, Laura E.; Spackman, Eldon; Noseworthy, Tom; Clement, Fiona

2017-01-01

Background: Recreational marijuana has been legalized in 11 jurisdictions; Canada will legalize marijuana by July 2018. With this changing landscape, there is a need to understand the public health risks associated with marijuana to support patient-care provider conversations, harm-reduction measures and evidence-informed policy. The objective of this work was to summarize the health effects of exposure to second- and third-hand marijuana smoke. Methods: In this systematic review, we searched 6 databases from inception to October 2017. Abstract and full-text review was conducted in duplicate. Studies were included if they were human, in vivo or in vitro studies with more than 1 case reported in English or French, and reported original, quantitative data. Three outcomes were extracted: 1) cannabinoids and cannabinoid metabolites in bodily fluids, 2) self-reported psychoactive effects and 3) eye irritation and discomfort. Results: Of the 1701 abstracts identified, 60 proceeded to full-text review; the final data set contained 15 articles. All of the included studies were of good to poor quality as assessed with the Downs and Black checklist. There is evidence of a direct relation between the tetrahydrocannabinol content of marijuana and effects on those passively exposed. This relation is mediated by several environmental factors including the amount of smoke, ventilation, air volume, number of marijuana cigarettes lit and number of smokers present. No evidence was identified assessing exposure to third-hand marijuana smoke or the health effects of long-term exposure. Interpretation: Exposure to second-hand marijuana smoke leads to cannabinoid metabolites in bodily fluids, and people experience psychoactive effects after such exposure. Alignment of tobacco and marijuana smoking bylaws may result in the most effective public policies. More research is required to understand the impact of exposure to third-hand smoke and the health effects of long-term exposure to second-hand smoke. PMID:29192095
Health effects of exposure to second- and third-hand marijuana smoke: a systematic review.

PubMed

Holitzki, Hannah; Dowsett, Laura E; Spackman, Eldon; Noseworthy, Tom; Clement, Fiona

2017-11-24

Recreational marijuana has been legalized in 11 jurisdictions; Canada will legalize marijuana by July 2018. With this changing landscape, there is a need to understand the public health risks associated with marijuana to support patient-care provider conversations, harm-reduction measures and evidence-informed policy. The objective of this work was to summarize the health effects of exposure to second- and third-hand marijuana smoke. In this systematic review, we searched 6 databases from inception to October 2017. Abstract and full-text review was conducted in duplicate. Studies were included if they were human, in vivo or in vitro studies with more than 1 case reported in English or French, and reported original, quantitative data. Three outcomes were extracted: 1) cannabinoids and cannabinoid metabolites in bodily fluids, 2) self-reported psychoactive effects and 3) eye irritation and discomfort. Of the 1701 abstracts identified, 60 proceeded to full-text review; the final data set contained 15 articles. All of the included studies were of good to poor quality as assessed with the Downs and Black checklist. There is evidence of a direct relation between the tetrahydrocannabinol content of marijuana and effects on those passively exposed. This relation is mediated by several environmental factors including the amount of smoke, ventilation, air volume, number of marijuana cigarettes lit and number of smokers present. No evidence was identified assessing exposure to third-hand marijuana smoke or the health effects of long-term exposure. Exposure to second-hand marijuana smoke leads to cannabinoid metabolites in bodily fluids, and people experience psychoactive effects after such exposure. Alignment of tobacco and marijuana smoking bylaws may result in the most effective public policies. More research is required to understand the impact of exposure to third-hand smoke and the health effects of long-term exposure to second-hand smoke. Copyright 2017, Joule Inc. or its licensors.
[Quality of life among people addicted to psychoactive substances participating in the opiate substitution treatment].

PubMed

Kotwas, Artur; Karakiewicz, Beata; Sein Anand, Jacek

2014-01-01

Opiate addiction remains a major threat to public health worldwide. It also had a number of negative consequences for the psychosocial and economic functioning of abusers. One of the most common addiction treatment method is maintenance methadone therapy. An important part of evaluating the effectiveness of the participation of a person addicted to methadone treatment is to assess the quality of life determined by participation in substitution therapy. Quality of life of persons addicted to psychoactive substances determined by socio-demographic situation. The study involved 234 outpatient addicts included in the methadone maintenance treatment programs in Szczecin, Warsaw and Lublin. It was based on a diagnostic survey performed using an original questionnaire and the SF-36 v2. In a research of subjective qual- ity of life, respondents obtained results at the level sufficient, higher values were obtained in the domains of physical than mental health. Respondents from Szczecin and Warszawa scored higher, statistically significant, the assessment than patients from Lublin. 1. Variation of respondents quality of life was conditioned by the place of performance of therapy. 2. Respondents had the greatest disparity in the subjective evaluation of physical and mental health. 3. Age was an important factor affecting the marks obtained by the respondents in the SF-36 v2.
Detecting a signal in the noise: monitoring the global spread of novel psychoactive substances using media and other open-source information†

PubMed Central

Young, Matthew M; Dubeau, Chad; Corazza, Ornella

2015-01-01

Objective To determine the feasibility and utility of using media reports and other open-source information collected by the Global Public Health Intelligence Network (GPHIN), an event-based surveillance system operated by the Public Health Agency of Canada, to rapidly detect clusters of adverse drug events associated with ‘novel psychoactive substances’ (NPS) at the international level. Methods and Results Researchers searched English media reports collected by the GPHIN between 1997 and 2013 for references to synthetic cannabinoids. They screened the resulting reports for relevance and content (i.e., reports of morbidity and arrest), plotted and compared with other available indicators (e.g., US poison control center exposures). The pattern of results from the analysis of GPHIN reports resembled the pattern seen from the other indicators. Conclusions The results of this study indicate that using media and other open-source information can help monitor the presence, usage, local policy, law enforcement responses, and spread of NPS in a rapid effective way. Further, modifying GPHIN to actively track NPS would be relatively inexpensive to implement and would be highly complementary to current national and international monitoring efforts. © 2015 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd. PMID:26216568
Risk Competence in Dealing With Alcohol and Other Drugs in Adolescence.

PubMed

Nagy, Ede; Verres, Rolf; Grevenstein, Dennis

2017-12-06

Adolescence is a critical phase for the development substance use patterns. We propose that individual competence in dealing with psychoactive substances is crucial for the development of healthy substance use behavior and prevention of substance misuse or addiction. We present a new concept of health related skills in dealing with alcohol and other drugs in adolescence, its operationalization and validation. Our conception of risk competence (RICO) consists of the four major factors being Reflective, Informed, Self-Controlled and Life-Oriented, and their sub-facets. Based on a sample of N = 753 adolescents we used classical test theory as well as item response theory to create a new measure of RICO. Validity was investigated in a new sample of N = 229 with regard to substance use, risk perception, and measures of personality (Big Five, sense of coherence, general self-efficacy). RICO contains 7 scales with 28 items that measure independent aspects of risk competence. Cross-sectional criterion validity for most of the scales could be shown. Conclusions/Importance: The new RICO scales are a valid measure of different aspects of risk competence in dealing with psychoactive substances. The questionnaire can be used in general research settings, but may also be applied to assess the effects of interventions.
Administrator turnover and quality of care in nursing homes.

PubMed

Castle, N G

2001-12-01

In this article, I examine the association between turnover of nursing home administrators and five important quality of care outcomes. The data came from a survey of 420 nursing facilities and the 1999 On-line Survey, Certification, and Reporting System. Using multivariate logistic regression analyses, I looked at the effects of turnover of administrators in nursing homes belonging to chain organizations and in nursing homes not belonging to chain organizations. I found the average annual turnover rate of administrators to be 43%. The multivariate logistic regression analyses show that in nursing homes belonging to chains, administrator turnover is associated with a higher than average proportion of residents who were catheterized, had pressure ulcers, and were given psychoactive drugs and with a higher than average number of quality-of-care deficiencies. In nursing homes not belonging to chains I found that turnover of administrators is associated with a higher than average proportion of residents who were restrained, were catheterized, had pressure ulcers, and were given psychoactive drugs. There is a need to improve understanding of how and why better outcomes are achieved in some nursing homes. This investigation serves to focus attention on nursing home administrators. I believe this study provides preliminary evidence that the turnover of administrators may have an important association with quality of care in nursing homes.
Menthol enhances nicotine-induced locomotor sensitization and in vivo functional connectivity in adolescence.

PubMed

Thompson, Matthew F; Poirier, Guillaume L; Dávila-García, Martha I; Huang, Wei; Tam, Kelly; Robidoux, Maxwell; Dubuke, Michelle L; Shaffer, Scott A; Colon-Perez, Luis; Febo, Marcelo; DiFranza, Joseph R; King, Jean A

2018-03-01

Mentholated cigarettes capture a quarter of the US market, and are disproportionately smoked by adolescents. Menthol allosterically modulates nicotinic acetylcholine receptor function, but its effects on the brain and nicotine addiction are unclear. To determine if menthol is psychoactive, we assessed locomotor sensitization and brain functional connectivity. Adolescent male Sprague Dawley rats were administered nicotine (0.4 mg/kg) daily with or without menthol (0.05 mg/kg or 5.38 mg/kg) for nine days. Following each injection, distance traveled in an open field was recorded. One day after the sensitization experiment, functional connectivity was assessed in awake animals before and after drug administration using magnetic resonance imaging. Menthol (5.38 mg/kg) augmented nicotine-induced locomotor sensitization. Functional connectivity was compared in animals that had received nicotine with or without the 5.38 mg/kg dosage of menthol. Twenty-four hours into withdrawal after the last drug administration, increased functional connectivity was observed for ventral tegmental area and retrosplenial cortex with nicotine+menthol compared to nicotine-only exposure. Upon drug re-administration, the nicotine-only, but not the menthol groups, exhibited altered functional connectivity of the dorsal striatum with the amygdala. Menthol, when administered with nicotine, showed evidence of psychoactive properties by affecting brain activity and behavior compared to nicotine administration alone.
Structure determination of butylone as a new psychoactive substance using chiroptical and vibrational spectroscopies.

PubMed

Spálovská, Dita; Králík, František; Kohout, Michal; Jurásek, Bronislav; Habartová, Lucie; Kuchař, Martin; Setnička, Vladimír

2018-05-01

Recently, there has been a worldwide substantial increase in the consumption of new psychoactive substances (NPS), compounds that mimic the structure of illicit drugs, such as amphetamines or ecstasy. The producers try to avoid the law by a slight modification of illicit structures, thereby developing dozens of temporarily legal NPS every year. The current trends in the detection and monitoring of such substances demand a fast and reliable analysis. Molecular spectroscopy represents a highly effective tool for the identification of NPS and chiroptical methods can provide further information on their 3D structure, which is the key for the determination of their biological activity. We present the first systematic study of NPS, specifically butylone, combining chiroptical and vibrational spectroscopies with ab initio calculations. According to density functional theory calculations, 6 stable lowest energy conformers of butylone were found and their molecular structure was described. For each conformer, the relative abundance based on the Boltzmann distribution was estimated, their population weighted spectra predicted and compared to the experimental results. Very good agreement between the experimental and the simulated spectra was achieved, which allowed not only the assignment of the absolute configuration, but also a precise description of the molecular structure. © 2018 Wiley Periodicals, Inc.
Expecting innovation: psychoactive drug primes and the generation of creative solutions.

PubMed

Hicks, Joshua A; Pedersen, Sarah L; Pederson, Sarah L; Friedman, Ronald S; McCarthy, Denis M

2011-08-01

Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed. (c) 2011 APA, all rights reserved.
Methodological Considerations in Social Cost Studies of Addictive Substances: A Systematic Literature Review.

PubMed

Verhaeghe, Nick; Lievens, Delfine; Annemans, Lieven; Vander Laenen, Freya; Putman, Koen

2016-01-01

Alcohol, tobacco, illicit drugs, and psychoactive pharmaceuticals' use is associated with a higher likelihood of developing several diseases and injuries and, as a consequence, considerable health-care expenditures. There is yet a lack of consistent methodologies to estimate the economic impact of addictive substances to society. The aim was to assess the methodological approaches applied in social cost studies estimating the economic impact of alcohol, tobacco, illicit drugs, and psychoactive pharmaceuticals. A systematic literature review through the electronic databases, Medline (PubMed) and Web of Science, was performed. Studies in English published from 1997 examining the social costs of the addictive substances alcohol, tobacco, illicit drugs, and psychoactive pharmaceuticals were eligible for inclusion. Twelve social cost studies met the inclusion criteria. In all studies, the direct and indirect costs were measured, but the intangible costs were seldom taken into account. A wide variety in cost items included across studies was observed. Sensitivity analyses to address the uncertainty around certain cost estimates were conducted in eight studies considered in the review. Differences in cost items included in cost-of-illness studies limit the comparison across studies. It is clear that it is difficult to deal with all consequences of substance use in cost-of-illness studies. Future social cost studies should be based on sound methodological principles in order to result in more reliable cost estimates of the economic burden of substance use.
Monitoring risk behaviour in adolescent pupils regarding consumption of psychoactive substances.

PubMed

Wojtyła-Buciora, Paulina; Klimberg, Aneta; Kapka-Skrzypczak, Lucyna; Diatczyk, Jarosław; Urbaniak, Monika; Ulatowska-Szostak, Ewa; Bołdowski, Tomasz; Wojtyła, Andrzej; Marcinkowski, Jerzy T

2017-06-06

Introduction. Taking psychoactive substances constitutes a significant problem for Public Health, particularly in preventing drug abuse and addiction. Objectives. To estimate the amount and incidence of drug consumption in middle and high school pupils, including the circumstances in which drug taking first started, and to determine pupils' knowledge about the consequences of taking psychoactive substances and designer drugs (DDs). Materials and methods. A randomised study was conducted throughout Poland on 9,360 pupils attending middle school (junior high school) in 2009 and 7,971 pupils from middle and high school pupils in 2011. The survey consisted of a questionnaire devised by the Chief Sanitary Inspectorate (GIS) and the replies obtained were subject to the relevant statistical analyses. Results. Drug taking was found to have increased between 2009-2011, especially among those attending high school; proportionally rising from 4% - 11%. The numbers who had ever taken designer drugs were 3% for middle school pupils and 4% from high school. Conclusions. 1) Adolescent drug consumption has increased, particularly in those of older age and in boys. 2) Despite the only brief interval for which designer drugs were legal, they have gained high popularity among the young. 3) Adolescents have insufficient knowledge about the dangers of using DDs. 4) Faced with the growing threat of a dynamic designer drug market, appropriate counter-measures in education and prevention are therefore necessary.
The Dynamic Environment of Crypto Markets: The Lifespan of New Psychoactive Substances (NPS) and Vendors Selling NPS

PubMed Central

Wadsworth, Elle; Drummond, Colin; Deluca, Paolo

2018-01-01

The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets and considers whether crypto markets are a reliable platform for the sale of NPS. Data was collected from 22 crypto markets that were accessed through the hidden web using the Onion Router (Tor). Data collection took place bimonthly from October 2015 to October 2016 as part of the CASSANDRA (Computer Assisted Solutions for Studying the Availability aNd DistRibution of novel psychoActive substances) project. In seven snapshots over 12 months, 808 unique vendors were found selling 256 unique NPS. The total number of individual NPS and vendors increased across the data collection period (increase of 93.6% and 71.6%, respectively). Only 24% (n = 61) of the total number of NPS and 4% (n = 31) of vendors appeared in every snapshot over the 12 months, whereas 21% (n = 54) of NPS and 45% (n = 365) of vendors only appeared once throughout the data collection. The individual NPS and vendors did not remain the same over the 12 months. However, the availability of NPS and vendors selling NPS grew. NPS consistently available on crypto markets could indicate popular substances. PMID:29547520

Perception of health risks among adolescents due to consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina.

PubMed

Pilav, A; Rudić, A; Branković, S; Djido, V

2015-07-01

This article describes the perception of health risks in adolescents due to the consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina (FBIH), as well as their observation of the behavior of their peers related to addictive behaviors. For the analysis was used a database from the European School Survey Project on Alcohol and Other Drugs (ESPAD) survey which was conducted in FBIH in 2011. The target population were students in the second grade of secondary schools in FBIH born in 1995 according to the ESPAD protocol. The total number of respondents from the cohort born in 1995 was 3813 students. The research results showed that the prevalence of risk perception due to the consumption of cigarettes, alcohol and psychoactive substances among adolescents in the FBIH is lower than the mean prevalence in countries which have implemented the ESPAD survey of 2011. PPreventive activities should be aimed at adolescent risk behaviours and empower them to make the right decisions that can have far reaching significance. Attention has to be paid to selective prevention that is directed towards individuals or subgroup of population where the risk of developing disorder is much higher than average. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
When good times go bad: managing ‘legal high’ complications in the emergency department

PubMed Central

Caffrey, Charles R; Lank, Patrick M

2018-01-01

Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get “legal highs.” Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of “legal highs,” or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka “designer drugs,” but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used “legal high” substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department. PMID:29302196
Suppression of human macrophage function in vitro by delta 9-tetrahydrocannabinol.

PubMed

Specter, S; Lancz, G; Goodfellow, D

1991-11-01

The ability of macrophages to function in the presence of delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was evaluated. THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. The effects of THC were concentration dependent, with inhibitory effects observed from 10 to 1 micrograms/ml or lower. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function(s) by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.
Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

PubMed

Breuer, Aviva; Haj, Christeene G; Fogaça, Manoela V; Gomes, Felipe V; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A; Hallak, Jaime C; Crippa, José A; Zuardi, Antonio W; Mechoulam, Raphael; Guimarães, Francisco S

2016-01-01

Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.
Dravet Syndrome

MedlinePlus

... and Drug Administration approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Dravet ... only small amount of the psychoactive element in marijuana and does not induce euphoria associated with the ...
[Use of psychoactive substances and risk sexual behavior].

PubMed

Vavrinková, B

2011-02-01

Present influence of illicit drug and alcohol on risk sexual behavior of young women in Prague and Central Bohemia. Prospective study. Department of Gynecology and Obstetrics, Teaching Hospital and 2nd Medical Faculty of Charles University in Prague. The study participants were 400 sexual active women between 16 and 35 years of age living in Prague and Central Bohemia. All participants were asked via questionnaire illicit drugs and alcohol experience, number of sexual partners, sexual behavior and use condom. Women using illicit drugs or alcohol had higher number of sexual partners. 1/3 said that drinking or drug use has influenced their decisions about sex and sexual behavior and unprotected sex. Use of psychoactive substances including alcohol influence negative sexual behavior. Cause escalated sexual activity and promiscuity, more frequently have risk and unprotected sex.
The use of HPLC-Q-TOF-MS for comprehensive screening of drugs and psychoactive substances in hair samples and several "legal highs" products.

PubMed

Aszyk, Justyna; Kot-Wasik, Agata

Non-targeted screening of drugs present in herbal products, known as "legal high" drugs and in hair as a biological matrix commonly used in toxicological investigations was accomplished with the use of high pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In total, 25 and 14 therapeutical drugs and psychoactive substances/metabolites were detected in investigated hair samples and herbal products, respectively. We demonstrate that the HPLC-Q-TOF methodology seems to be a powerful tool in the qualitative analysis applied in identification of these designer drugs, thus enabling a laboratory to stay-up-to-date with the drugs that are being sold as legal high products on black market.
[Hallucinogenic mushrooms].

PubMed

Reingardiene, Dagmara; Vilcinskaite, Jolita; Lazauskas, Robertas

2005-01-01

The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.
Behavioural pharmacology of the α5-GABAA receptor antagonist S44819: Enhancement and remediation of cognitive performance in preclinical models.

PubMed

Gacsályi, István; Móricz, Krisztina; Gigler, Gábor; Wellmann, János; Nagy, Katalin; Ling, István; Barkóczy, József; Haller, József; Lambert, Jeremy J; Szénási, Gábor; Spedding, Michael; Antoni, Ferenc A

2017-10-01

Previous work has shown that S44819 is a novel GABAA receptor (GABA A R) antagonist, which is selective for extrasynaptic GABA A Rs incorporating the α5 subunit (α5-GABA A Rs). The present study reports on the preclinical neuropsychopharmacological profile of S44819. Significantly, no sedative or pro-convulsive side effects of S44819 were found at doses up to 30 mg/kg i.p. Object recognition (OR) memory in intact mice was enhanced by S44819 (0.3 mg/kg p.o.) given before the acquisition trial. Mice treated with phencyclidine for two weeks and tested six days after the cessation of treatment failed to show OR memory. This deficit was corrected by a single administration of S44819 (0.1, 0.3 or 1 mg/kg p.o.) prior to the acquisition trial. The amnestic effect of ketamine in rats tested in the eight-arm radial maze (reference and working memory versions) was blocked by S44819 (3 mg/kg p.o.). Extinction of cued fear was preserved during treatment with S44819 (3 mg/kg/diem i.p.). Administration of S44819 had no significant effect in the Vogel-conflict test, the elevated plus maze, the forced swim, the marble-burying and the tail-suspension tests. In contrast, anxiolytic/antidepressant-like effects of the compound were found in paradigms that have mnemonic components, such as social interaction, fear-potentiated startle and social avoidance induced by negative life experience. In summary, S44819 enhanced intact recognition memory and ameliorated memory deficits induced by inhibition of NMDA receptors. Anxiolytic/antidepressant efficacy was limited to paradigms involving cognitive function. In conclusion, S44819 is a novel psychoactive pro-cognitive compound with potential as a therapeutic agent in dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.
Lennox-Gastaut Syndrome

MedlinePlus

... and Drug Administration approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Lennox- ... only small amount of the psychoactive element in marijuana and does not induce euphoria associated with the ...
[Therapeutic potential of Cannabis sativa].

PubMed

Avello L, Marcia; Pastene N, Edgar; Fernández R, Pola; Córdova M, Pia

2017-03-01

Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.
Effects of harmane (1-methyl-beta-carboline) on neurons in the nucleus accumbens of the rat.

PubMed

Ergene, E; Schoener, E P

1993-04-01

Harmane, a beta-carboline alkaloid reported to exert locomotor and psychoactive effects, is found in certain plants and also has been shown to exist in the mammalian brain as an endogenous substance. In this study, the effects of locally perfused harmane were examined on spontaneous neuronal activity in the nucleus accumbens of urethane-anesthetized rats. Extracellular single-unit recording, coupled with push-pull perfusion, enabled the discrimination of specific, dose-related effects of harmane across a wide concentration range. At lower concentrations (10(-9)-10(-11) M), excitation prevailed, while at higher concentrations (10(-8)-10(-6) M) depression was most pronounced. These findings suggest a neuromodulatory role for harmane in the forebrain reward system.
Phase I metabolism of the recently emerged synthetic cannabinoid CUMYL-PEGACLONE and detection in human urine samples.

PubMed

Mogler, Lukas; Wilde, Maurice; Huppertz, Laura M; Weinfurtner, Georg; Franz, Florian; Auwärter, Volker

2018-05-01

Indole-, indazole-, or azaindole-based synthetic cannabinoids (SCs), bearing a cumyl substituent are a widespread, recreationally used subgroup of new psychoactive substances (NPS). The latest cumyl-derivative, CUMYL-PEGACLONE, emerged in December 2016 on the German drug market. The substance features a novel γ-carboline core structure, which is most likely synthesized to bypass generic legislative approaches to control SCs by prohibiting distinct core structures. Using liquid chromatography-tandem mass spectrometry and liquid chromatography-high resolution mass spectrometry techniques, the main in vivo phase I metabolites of this new substance were detected. A pooled human liver microsome assay was applied to generate in vitro reference spectra of CUMYL-PEGACLONE phase I metabolites. Additionally, 30 urine samples were investigated leading to 22 in vivo metabolites. A metabolite mono-hydroxylated at the γ-carbolinone core system and a metabolite with an additional carbonyl group at the pentyl side chain were evaluated as highly specific and sensitive markers to proof CUMYL-PEGACLONE uptake. Moreover, 3 immunochemical assays commonly used for SC screening in urine were tested for their capability of detecting the new drug but failed due to insufficient cross-reactivity. Copyright © 2018 John Wiley & Sons, Ltd.
Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of 'legal high' packages containing synthetic cathinones.

PubMed

Araújo, Ana Margarida; Valente, Maria João; Carvalho, Márcia; Dias da Silva, Diana; Gaspar, Helena; Carvalho, Félix; de Lourdes Bastos, Maria; Guedes de Pinho, Paula

2015-05-01

The world's status quo on recreational drugs has dramatically changed in recent years due to the rapid emergence of new psychoactive substances (NPS), represented by new narcotic or psychotropic drugs, in pure form or in preparation, which are not controlled by international conventions, but that may pose a public health threat comparable with that posed by substances listed in these conventions. These NPS, also known as 'legal highs' or 'smart drugs', are typically sold via Internet or 'smartshops' as legal alternatives to controlled substances, being announced as 'bath salts' and 'plant feeders' and is often sought after for consumption especially among young people. Although NPS have the biased reputation of being safe, the vast majority has hitherto not been tested and several fatal cases have been reported, namely for synthetic cathinones, with pathological patterns comparable with amphetamines. Additionally, the unprecedented speed of appearance and distribution of the NPS worldwide brings technical difficulties in the development of analytical procedures and risk assessment in real time. In this study, 27 products commercialized as 'plant feeders' were chemically characterized by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. It was also evaluated, for the first time, the in vitro hepatotoxic effects of individual synthetic cathinones, namely methylone, pentedrone, 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV). Two commercial mixtures ('Bloom' and 'Blow') containing mainly cathinone derivatives were also tested, and 3,4-methylenedioxymethamphetamine (MDMA) was used as the reference drug. The study allowed the identification of 19 compounds, showing that synthetic cathinones are the main active compounds present in these products. Qualitative and quantitative variability was found in products sold with the same trade name in matching or different 'smartshops'. In the toxicity studies performed in primary cultured rat hepatocytes, pentedrone and MDPV proved to be the most potent individual agents, with EC50 values of 0.664 and 0.742 mM, respectively, followed by MDMA (EC50 = 0.754 mM). 4-MEC and methylone were the least potent substances, with EC50 values significantly higher (1.29 and 1.18 mM, respectively; p < 0.05 vs. MDMA). 'Bloom' and 'Blow' showed hepatotoxic effects similar to MDMA (EC50 = 0.788 and 0.870 mM, respectively), with cathinones present in these mixtures contributing additively to the overall toxicological effect. Our results show a miscellany of psychoactive compounds present in 'legal high' products with evident hepatotoxic effects. These data contribute to increase the awareness on the real composition of 'legal high' packages and unveil the health risks posed by NPS.
[Comorbidity in adolescence: simultaneous declaration of depressive, eating, obsessive-compulsive symptoms and use of psychoactive substances in the general population of 17 year old students in a big city].

PubMed

Modrzejewska, Renata

2010-01-01

To determine whether the following symptoms: depressive symptoms, eating disorder symptoms and obsessive-compulsive symptoms among adolescents in Kraków secondary schools are associated with an increased risk of psychoactive substance use. A representative sample of the population of Kraków secondary school pupils was tested. A two-stage draw method identified a group of 2034 2nd form pupils of all types of secondary schools: grammar schools, technical schools and vocational schools (17-year olds). They were tested using the following screening questionnaires: Beck Depression Scale, EAT-26 eating disorders scale, Obsessive-compulsive disorder (Leyton) scale and the author's drug questionnaire. The incidence of depressive symptoms among boys and girls is associated with an increased risk of alcohol use (74.8% among depressive boys versus 65.8% in the depressive group of girls), cigarette smoking (42.7% vs. 46.7%) and drug use (29.0% vs. 18.6%). All of the relationships are statistically significant in both sexes. 41.7% depressive boys admit to smoking, vs. only 32.6% in the non-depressive group. In the girls' group, these relationships are as follows: 46.7% versus 32.1%. The relationships are statistically significant in both sexes. The incidence of eating disorder symptoms among boys and girls is associated with a higher risk of alcohol use (respectively: 73.5% vs. 61.9%), cigarette smoking (42.1% vs. 46.9%), and drug use (31.6% versus 21.5%). Compared with a group of young people without eating disorder symptoms, the relationships are of statistical significance. Comorbidity of the following symptoms was found: depressive symptoms, eating disorder symptoms, obsessive-compulsive symptoms and symptoms of psychoactive substance use. The presence of depressive symptoms increases the risk of the use of psychoactive substances, especially alcohol and tobacco, to a lesser extent--drugs, both in the boys and in the girls. The presence of eating disorder symptoms increases the risk of smoking and drug use among both boys and girls.
Assessing self-reported use of new psychoactive substances: The impact of gate questions.

PubMed

Palamar, Joseph J; Acosta, Patricia; Calderón, Fermín Fernández; Sherman, Scott; Cleland, Charles M

2017-09-01

New psychoactive substances (NPS) continue to emerge; however, few surveys of substance use ask about NPS use. Research is needed to determine how to most effectively query use of NPS and other uncommon drugs. To determine whether prevalence of self-reported lifetime and past-year use differs depending on whether or not queries about NPS use are preceded by "gate questions." Gate questions utilize skip-logic, such that only a "yes" response to the use of specific drug class is followed by more extensive queries of drug use in that drug class. We surveyed 1,048 nightclub and dance festival attendees (42.6% female) entering randomly selected venues in New York City in 2016. Participants were randomized to gate vs. no gate question before each drug category. Analyses focus on eight categories classifying 145 compounds: NBOMe, 2C, DOx, "bath salts" (synthetic cathinones), other stimulants, tryptamines, dissociatives, and non-phenethylamine psychedelics. Participants, however, were asked about specific "bath salts" regardless of their response to the gate question to test reliability. We examined whether prevalence of use of each category differed by gate condition and whether gate effects were moderated by participant demographics. Prevalence of use of DOx, other stimulants, and non-phenethylamine psychedelics was higher without a gate question. Gate effects for other stimulants and non-phenethylamine psychedelics were larger among white participants and those attending parties less frequently. Almost one in ten (9.3%) participants reporting no "bath salt" use via the gate question later reported use of a "bath salt" such as mephedrone, methedrone, or methylone. Omitting gate questions may improve accuracy of data collected via self-report.
Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study.

PubMed

Riba, Jordi; McIlhenny, Ethan H; Bouso, José Carlos; Barker, Steven A

2015-05-01

N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors. Copyright © 2014 John Wiley & Sons, Ltd.
A urinary test procedure for identification of cannabidiol in patients undergoing medical therapy with marijuana.

PubMed

Wertlake, Paul T; Henson, Michael D

2016-01-01

Marijuana is classified by the Drug Enforcement Agency (DEA) as Schedule I, drugs having no accepted medical value. Twenty-three states and the District of Columbia have legalized medical marijuana. This conflict inhibits physicians from prescribing marijuana and the systematic study of marijuana in medical care. This study concerns the use of the clinical laboratory as a resource for physicians recommending cannabidiol (CBD) to patients, or for patients using medical marijuana. Marijuana containing delta-9-tetrahydrocannabinol (THC) is psychoactive. CBD is not psychoactive. CBD is reported to have medical benefit for seizure control, neurologic disorders including multiple sclerosis, neuropathic pain and pain associated with cancer. Use of opiates leads to increasing dosage over time that may cause respiratory depression. The Medical Board of California has termed this a serious public health crisis of addiction, overdose, and death. Is it feasible that CBD might alleviate persistent, severe pain and therefore diminished opiate use? Further study is needed to determine medical effectiveness of CBD including the effect on concurrent opiate therapy due to competition for receptor sites. This study is the application of a gas chromatography mass spectrometry procedure adapted for use in our laboratory, to detect CBD in urine. The intended use is as a tool for physicians to assess that marijuana being used by a patient is of a composition likely to be medically effective. A law ensuring physicians freedom from federal prosecution would provide confidence essential to formal study of medical uses of marijuana and treatment of clinical problems. Detection of CBD in a urine sample would be a convenient test for such confirmation.
Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers

PubMed Central

Riba, Jordi; Anderer, Peter; Morte, Adelaida; Urbano, Gloria; Jané, Francesc; Saletu, Bernd; Barbanoj, Manel J

2002-01-01

Aims Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and β-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity. Methods Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg−1 body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Results Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were −20.20±15.23 µV2 and −2.70±2.21 µV2 for total power and theta power, respectively. Relative power decreased in the delta (−1.20±1.31% after 120 min at P3) and theta (−3.30±2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00±0.88% after 90 min at P3) and beta-4 (0.30±0.24% after 90 min at P3) subbands. Finally, an increase was also seen for the centroid of the total activity and its deviation. EEG modifications began as early as 15–30 min, reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4–6 h after administration. Conclusions The central effects of ayahuasca could be objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of previously reported subjective effects. The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system. PMID:12047486
Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

PubMed

Hermanns-Clausen, Maren; Müller, Dieter; Kithinji, Josephine; Angerer, Verena; Franz, Florian; Eyer, Florian; Neurath, Hartmud; Liebetrau, Gesine; Auwärter, Volker

2018-06-01

In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs. A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre. Serum and/or urine samples of ED patients were analyzed using LC-MS/MS. Forty four patients (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively. In 19 of the cases, more than one SC was present. Other psychoactive substances (mainly amfetamines) were identified in seven cases, but in five out of these in urine samples only. Based on the Poison Severity Score, severity of poisoning was minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%), generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred in 15 cases (34%). The prevalence of certain neuropsychiatric symptoms was higher in our study than in former reports after the intake of SCs of the aminoalkylindole-type (first generation) SCs. In addition, severe poisoning and duration of symptoms were also higher. In this study, the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA ("third generation of SCs") seem to be associated with more severe clinical toxicity than was previously reported in patients exposed to earlier generation SCs such as JWH-018. However, this observation needs to be confirmed with a larger cohort of patients with analytically confirmed abuse of third generation SCs. The rapid turnover of SCs on the drug market together with the occurrence of SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the unexpectedly high frequency of neuropsychiatric symptoms.

Patterns of drug use from adolescence to young adulthood: II. Sequences of progression.

PubMed Central

Yamaguchi, K; Kandel, D B

1984-01-01

Major pathways of progression among legal, illegal, and medically prescribed psychoactive drugs from adolescence to young adulthood are described. The data are based on a follow-up cohort of former adolescents representative of high school students in grades 10 and 11 in New York State who were reinterviewed nine years later at ages 24-25. Various models of progression are tested for their goodness of fit. The patterns formerly observed in adolescence involving progression from one class of legal drug (either alcohol or cigarettes) to marijuana to the use of other illicit drugs appear in the transitional period into young adult, with an additional stage, that of prescribed psychoactive drugs. Some differences appear between men and women, with cigarettes more important for women than for men in the total progression. PMID:6742252
Association between bullying victimization and substance use among college students in Spain.

PubMed

Caravaca Sánchez, Francisco; Navarro Zaragoza, Javier; Luna Ruiz-Cabello, Aurelio; Falcón Romero, María; Luna Maldonado, Aurelio

2016-06-14

The purpose of this study is to analyze the prevalence and association between victimization and substance use among the university population in the southeast of Spain in a sample of 543 randomly selected college students (405 females and 138 males with an average age of 22.6 years). As a cross-sectional study, data was collected through an anonymous survey to assess victimization and drug use over the last 12 months. Results indicated that 62.2% of college students reported bullying victimization and 82.9% consumed some type of psychoactive substance, and found a statistically significant association between both variables measured. Additionally, logistic regression analysis confirmed the association between psychoactive substance use and different types of victimization. Our findings confirm the need for prevention to prevent this relation between victimization and substance use.
[Levels of psilocybin and psilocin in various types of mushrooms].

PubMed

Stríbrný, J; Borovicka, J; Sokol, M

2003-07-01

Psilocin and psilocybin are psychoactive components of mushrooms of the genus Psilocybe and many others (Panaeolus, Inocybe, Pluteus etc.). In our republic, several species of Psilocybe with a high content of these components can be found. In the present study, we give a semiquantitative content of psilocin and psilocybin in some of our mushrooms in dry substance (Psilocybe semilanceata, Psilocybe bohemica, Psilocybe arcana, Psilocybe cyanescens, Panaeolus acuminatus sensu Ricken, Inocybe haemacta and Pluteus salicinus). For quantification, the GC/MS instrumentation was applied. Psilocin and psilocybin were silylated by the derivatization agent N-methyl-N-trimet-hylsilyltrifluoroacetamide. As an internal standard, 5-methoxytryptamin was used. The results of this study prove the presence of at least three species of Psilocybe with a high content of psychoactive components growing in our republic: Psilocybe semilanceata, Psilocybe bohemica and Psilocybe arcana.
Headspace analysis of new psychoactive substances using a Selective Reagent Ionisation-Time of Flight-Mass Spectrometer

PubMed Central

Acton, W. Joe; Lanza, Matteo; Agarwal, Bishu; Jürschik, Simone; Sulzer, Philipp; Breiev, Kostiantyn; Jordan, Alfons; Hartungen, Eugen; Hanel, Gernot; Märk, Lukas; Mayhew, Chris A.; Märk, Tilmann D.

2014-01-01

The rapid expansion in the number and use of new psychoactive substances presents a significant analytical challenge because highly sensitive instrumentation capable of detecting a broad range of chemical compounds in real-time with a low rate of false positives is required. A Selective Reagent Ionisation-Time of Flight-Mass Spectrometry (SRI-ToF-MS) instrument is capable of meeting all of these requirements. With its high mass resolution (up to m/Δm of 8000), the application of variations in reduced electric field strength (E/N) and use of different reagent ions, the ambiguity of a nominal (monoisotopic) m/z is reduced and hence the identification of chemicals in a complex chemical environment with a high level of confidence is enabled. In this study we report the use of a SRI-ToF-MS instrument to investigate the reactions of H3O+, O2+, NO+ and Kr+ with 10 readily available (at the time of purchase) new psychoactive substances, namely 4-fluoroamphetamine, methiopropamine, ethcathinone, 4-methylethcathinone, N-ethylbuphedrone, ethylphenidate, 5-MeO-DALT, dimethocaine, 5-(2-aminopropyl)benzofuran and nitracaine. In particular, the dependence of product ion branching ratios on the reduced electric field strength for all reagent ions was investigated and is reported here. The results reported represent a significant amount of new data which will be of use for the development of drug detection techniques suitable for real world scenarios. PMID:25844048
Which psychoactive prescription drugs are illegally obtained and through which ways of acquisition? About OPPIDUM survey.

PubMed

Frauger, Elisabeth; Nordmann, Sandra; Orleans, Veronica; Pradel, Vincent; Pauly, Vanessa; Thirion, Xavier; Micallef, Joëlle

2012-08-01

The objective of the study was to determine which psychoactive prescription drugs are illegally obtained and through which ways of acquisition. OPPIDUM is an annual national study. It is based on specialized care centers that included subjects presenting a drug dependency or under opiate maintenance treatment. All their psychoactive substances consumed are reported. This work focuses on the different ways of acquisition specially the illegal ways of acquisition (bought on the street, forged prescription, stolen, given, internet). For each medication illegally obtained, a ratio has been calculated (number of illegal acquisitions divided by the number of described acquisitions). In 2008, 5542 subjects have been included and have described the consumption of 11 027 substances including 63.8% of prescription drugs. Among them, 11% were illegally obtained. The different illegal acquisition ways were 'street market' (77.6%), 'gift' (16.6%), 'theft' (2.3%), 'forged prescription' (2.3%), and 'internet' (0.7%). The third first drugs illegally obtained were high dosage buprenorphine, methadone, and clonazepam. Some prescription drugs, less consumed, have an important ratio of illegal acquisition like ketamine, flunitrazepam, morphine, trihexyphenidyl, or methylphenidate. This study confirms that theft, forged prescription and internet are few used and permits to highlight diversion of prescription drugs. It is important to inform healthcare professionals on the different prescription drugs that are illegally obtained. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.
Ethnomycology, biochemistry, and cultivation of Psilocybe samuiensis Guzmán, Bandala and Allen, a new psychoactive fungus from Koh Samui, Thailand.

PubMed

Gartz, J; Allen, J W; Merlin, M D

1994-07-08

Several specimens of Psilocybe and Copelandia species in Koh Samui, Thailand were recently collected for herbarium deposit and scientific study. This paper presents an ethnomycological and biochemical study of one of the species; P. samuiensis Guzmán, Bandala and Allen, a new psychoactive gill fungus reported from Thailand. Mycelium for the cultivation of P. samuiensis was obtained on 6% malt agar from the spores of a dried specimen. The growth of P. samuiensis was similar to that of P. tampanensis Guzmán and Pollock, but more rapid than the mycelium of P. semilanceata (Fr.:Sacc.) Kumm. Laboratory analyses indicates that the alkaloid content in cultured fruit bodies of P. samuiensis is of the same order of magnitude as that found in naturally occurring mushrooms of this species. HPLC analyses of both naturally occurring and in vitro cultivated fruit bodies of P. samuiensis revealed high concentrations of psilocybin and psilocin. Small amounts of baeocystin were also detected. Psilocybin levels varied from 0.23% up to 0.90%. The psilocybin content was highest in the caps. Psilocybin was also found in the cultured non-bluing mycelia of P. samuiensis and varied from 0.24% to 0.32% dry weight. The relative alkaloidal content of psilocybin, psilocin, and baeocystin found in P. samuiensis was similar to that measured in many other psychoactive fungi species, but completely different from that found in P. semilanceata.
Psychoactive drug advertising: a comparison of technical information from three countries: Brazil, United States and United Kingdom.

PubMed

Mastroianni, Patricia de Carvalho; Galduróz, José Carlos Fernandes; Carlini, Elisaldo Araujo

2005-09-01

Studies carried out in the 1970s and 1980s showed that there were country-dependent disparities in the information given for the same drug in medical advertisements. National and international regulations have been published to do away with such disparities and to foster the rational use of drugs. The purpose of this study was to compare the information contained in psychoactive drug advertisements published in psychiatric journals in Brazil, the United States and the United Kingdom, before and subsequent to the publication of the United States Export Act, in 1986, the WHO criteria, in 1988, and the Brazilian Sanitary Surveillance Agency Resolution no. 102, in 2000. TYPE OF STUDY AND SETTING: Content analysis, at Centro Brasileiro de Informações sobre Drogas Psicotrópicas (Cebrid). We gathered advertisements from Brazilian, American and British psychiatry periodicals published before and after each ruling. We analyzed a total of twenty-four Brazilian advertisements that were for the same psychoactive drugs as advertised in American and/or British publications from the same period. We observed that Brazilian advertisements omitted information on usage restrictions, such as contraindications, adverse reactions, interactions, warnings and precautions, and that such information was present in American and British advertisements. The data suggest that disparities in the information given for the same drug still persist. The information depends on the country in which each drug is marketed. The legislation is insufficient for eradicating such disparities.
The impact of the Psychoactive Substances Act 2016 on the online availability of MDMB-CHMICA.

PubMed

Haden, M; Wood, D M; Dargan, P I

2017-10-01

In May 2016, the UK Government enacted the Psychoactive Substances Act which made it an offense to produce or supply many drugs including new psychoactive substances (NPS). We aimed to assess the impact of the Act on the availability of the synthetic cannabinoid receptor agonist methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB-CHMICA) from internet-based suppliers. Internet snapshot availability study. We conducted two snapshot availability surveys looking at the number of websites offering to sell MDMB-CHMICA: the first in March prior to implementation of the Act and the second in June, 1 month post-implementation. In March and June 2016, we identified 47 and 38 websites, respectively, which offered to sell MDMB-CHMICA. There were no significant differences in the price of the drug nor the forms available for purchase. In the June survey there was a significant decrease in the number of websites which openly stated they were based in the UK (from 14 down to 2), three websites stated that they did not supply customers based in the UK and two websites stated they had ceased sales of MDMB-CHMICA due to the Act. This study showed a small but limited reduction in the availability of MDMB-CHMICA from internet-based suppliers following implementation of the Act. © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

PubMed

Shannon, Scott; Opila-Lehman, Janet

2015-12-01

This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects. The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use. The specific use of CBD for marijuana reduction has not been widely studied. The patient was a 27-y-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana use. In the described intervention, the only change made to the patient's treatment was the addition of CBD oil with the dosage gradually decreasing from 24 to 18 mg. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.
Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action

PubMed Central

Maione, Sabatino; Piscitelli, Fabiana; Gatta, Luisa; Vita, Daniela; De Petrocellis, Luciano; Palazzo, Enza; de Novellis, Vito; Di Marzo, Vincenzo

2011-01-01

BACKGROUND AND PURPOSE Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. EXPERIMENTAL APPROACH Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. KEY RESULTS Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB1 adenosine A1 and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CONCLUSIONS AND IMPLICATIONS CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action. PMID:20942863
The diverse reasons for using Novel Psychoactive Substances - A qualitative study of the users' own perspectives.

PubMed

Soussan, Christophe; Andersson, Martin; Kjellgren, Anette

2018-02-01

The increasing number of legally ambiguous and precarious Novel Psychoactive Substances (NPS) constitutes a challenge for policy makers and public health. Scientific and more in-depth knowledge about the motivations for using NPS is scarce and often consist of predetermined, non-systematic, or poorly described reasons deduced from top-down approaches. Therefore, the aim of the present study was to explore and characterize the users' self-reported reasons for NPS use inductively and more comprehensively. The self-reported reasons of a self-selected sample of 613 international NPS users were collected via an online survey promoted at the international drug discussion forum bluelight.org and later analyzed qualitatively using inductive thematic analysis. The analysis showed that the participants used NPS because these compounds reportedly: 1) enabled safer and more convenient drug use, 2) satisfied a curiosity and interest about the effects, 3) facilitated a novel and exciting adventure, 4) promoted self-exploration and personal growth, 5) functioned as coping agents, 6) enhanced abilities and performance, 7) fostered social bonding and belonging, and 8) acted as a means for recreation and pleasure. The consumption of NPS was also driven by 9) problematic and unintentional use. The present study contributed to a more comprehensive understanding of the users' own and self-reported reasons for using NPS, which needs to be acknowledged not only in order to minimize drug related harm and drug user alienation but also to improve prevention efforts and reduce the potentially counter-intuitive effects of strictly prohibitive policies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Current challenges and problems in the field of new psychoactive substances in Germany from a law enforcement perspective.

PubMed

Duffert, Anna

2014-01-01

Over the last few years, a range of so-called new psychoactive substances (NPS) have established themselves on the German recreational drug scene, causing increased concern. At the same time, a great number of Internet shops have come into existence offering these substances for sale online, ensuring a high level of availability. A number of these substances derived from pharmaceutical research which did not result in marketing authorization, presumably due to unfavourable properties. There are hardly any reliable data on long-term health damage, addictive potential, and other aspects of these scientifically unexplored substances. A number of fatal intoxications have also become known. As a rule, the mostly young consumers do not know what substance they are taking and in what concentration, thus exposing themselves to incalculable health risks and consequences. The punishability of the handling of NPS depends on the actual content: the Narcotic Drugs Act (BtMG) is applicable if a product contains narcotic drugs. If similarly effective substances are contained, which are not classified as narcotic drugs, the (penal) provisions of the Medicinal Products Act might be applicable, if the product has a pharmaceutical effect. Experience gained so far has shown that manufacturers of these intoxicating substances react immediately to inclusions in the German BtMG and put new substances on the market which are chemically similar to the known substances thus circumventing legislation. In view of the immense variety of NPS and the enormous profits derived from their sale, an end to this development is not in sight. Copyright © 2014 John Wiley & Sons, Ltd.
New psychoactive substances legislation in Ireland - Perspectives from academia.

PubMed

Kavanagh, Pierce V; Power, John D

2014-01-01

The emergence of 'legal highs' or 'new psychoactive substances' (NPS) on the Irish market is reflective of their appearance in many countries, with some notable exceptions. The official response to the situation is examined here by looking at Irish controlled drugs legislation and drug enforcement policies as enacted in recent years and their effects on academic research on NPS. The philosophy and practice of outright bans of scheduled substances has not been effective in delivering the stated aims of illicit drug control, namely harm reduction. With these legislative changes, we have witnessed the removal of the 'legitimate' sale and open marketing of a number of NPS to the general public in commercial retail premises. However, as legislation was enacted, suppliers and vendors rapidly changed the contents of their legal high products from now controlled to non-controlled substances. We have found that it is administratively challenging to perform scientific research on controlled substances at academic institutions. It is desirable to gather analytical, pharmacological, and toxicological data on these substances as they emerge on the market but due to the restrictive nature of licensing requirements, once a substance or generic class of substances is controlled, this becomes more difficult. The facts that any quantity of substance, no matter how small, is controlled, the nomenclature used to describe compounds is not consistent within the enacted legislation and the use of catch-all classes of compounds with the intention of controlling many similar molecular structures, all create problematic issues for academic researchers. Copyright © 2014 John Wiley & Sons, Ltd.
[Sexuality, heart and chocolate].

PubMed

Bianchi-Demicheli, F; Sekoranja, L; Pechère-Bertschi, A

2013-03-20

All along the history, many kinds of magic and aphrodisiac properties were attributed to the chocolate. Because of the presence of certain active substances, cacao and chocolate are supposed to have some potentially beneficial effects on human health, particularly on cardiovascular system. Containing flavoniods, cacao and its products have antioxidant, anti-inflammatory, anti-atherogenic, anti-thrombotic, antihypertensive and neuroprotective effects, as well as influence on insulin sensitivity, vascular endothelial function, and activation of nitric oxide. Other molecules, like methyxantin, biogenic amines and cannabinoid-like fatty acids, may have a psychoactive action. Synergic effect of all these substances could have a positive direct and indirect influence on sexual health and function. Nevertheless, randomized studies are needed to confirm these hypotheses and to elaborate recommendations about cacao consumption.
Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

PubMed Central

Fogaça, Manoela V.; Gomes, Felipe V.; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A.; Hallak, Jaime C.; Crippa, José A.; Zuardi, Antonio W.; Guimarães, Francisco S.

2016-01-01

Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. PMID:27416026
Cannabis and its effects on driving skills.

PubMed

Bondallaz, Percy; Favrat, Bernard; Chtioui, Haïthem; Fornari, Eleonora; Maeder, Philippe; Giroud, Christian

2016-11-01

Traffic policies show growing concerns about driving under the influence of cannabis, since cannabinoids are one of the most frequently encountered psychoactive substances in the blood of drivers who are drug-impaired and/or involved in accidents, and in the context of a legalization of medical marijuana and of recreational use. The neurobiological mechanisms underlying the effects of cannabis on safe driving remain poorly understood. In order to better understand its acute and long-term effects on psychomotor functions involved in the short term ability and long-term fitness to drive, experimental research has been conducted based on laboratory, simulator or on-road studies, as well as on structural and functional brain imaging. Results presented in this review show a cannabis-induced impairment of actual driving performance by increasing lane weaving and mean distance headway to the preceding vehicle. Acute and long-term dose-dependent impairments of specific cognitive functions and psychomotor abilities were also noted, extending beyond a few weeks after the cessation of use. Some discrepancies found between these studies could be explained by factors such as history of cannabis use, routes of administration, dose ranges, or study designs (e.g. treatment blinding). Moreover, use of both alcohol and cannabis has been shown to lead to greater odds of making an error than use of either alcohol or cannabis alone. Although the correlation between blood or oral fluid concentrations and psychoactive effects of THC needs a better understanding, blood sampling has been shown to be the most effective way to evaluate the level of impairment of drivers under the influence of cannabis. The blood tests have also shown to be useful to highlight a chronic use of cannabis that suggests an addiction and therefore a long-term unfitness to drive. Besides blood, hair and repeated urine analyses are useful to confirm abstinence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Olanzapine as the ideal "trip terminator"? Analysis of online reports relating to antipsychotics' use and misuse following occurrence of novel psychoactive substance-related psychotic symptoms.

PubMed

Valeriani, Giuseppe; Corazza, Ornella; Bersani, Francesco Saverio; Melcore, Claudia; Metastasio, Antonio; Bersani, Giuseppe; Schifano, Fabrizio

2015-07-01

The pharmacological self-management of novel psychoactive substance (NPS)-induced psychopathological consequences represents a fast growing phenomenon. This is facilitated by the frequent sharing of NPS intake experiences online and by the ease of access to a range of psychotropic medications from both the online and street market. Olanzapine is anecdotally reported by Web users to be the most frequent self-prescribed medication to cope with NPS-induced psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for this purpose. Exploratory qualitative searches of 163 discussion fora/specialized websites have been carried out in four languages (English, German, Spanish, and Italian) in the time frame November 2012-2013. Most NPS-users allegedly self administer with olanzapine to manage related psychotic crises/"bad trips". This may be typically taken only for a few days, at a dosage range of 5-50 mg/day. Only a few research studies have formally assessed the effectiveness of olanzapine and indeed of other second-generation antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from a range of pro drug websites as being the "ideal" molecule to terminate "bad trips". Health professionals should be informed about the risks related to olanzapine misuse. Copyright © 2015 John Wiley & Sons, Ltd.
The Relationship between Multiple Substance Use, Perceived Academic Achievements, and Selected Socio-Demographic Factors in a Polish Adolescent Sample

PubMed Central

Mazur, Joanna; Tabak, Izabela; Dzielska, Anna; Wąż, Krzysztof; Oblacińska, Anna

2016-01-01

Predictors of high-risk patterns of substance use are often analysed in relation to demographic and school-related factors. The interaction between these factors and the additional impact of family wealth are still new areas of research. The aim of this study was to find determinants of the most common patterns of psychoactive substance use in mid-adolescence, compared to non-users. A sample of 1202 Polish students (46.1% boys, mean age of 15.6 years) was surveyed in 2013/2014. Four patterns of psychoactive substance use were defined using cluster analysis: non-users—71.9%, mainly tobacco and alcohol users—13.7%, high alcohol and cannabis users—7.2%, poly-users—7.2%. The final model contained the main effects of gender and age, and one three-way (perceived academic achievement × gender × family affluence) interaction. Girls with poor perception of school performance (as compared to girls with better achievements) were at significantly higher risk of being poly-users, in both less and more affluent families (adjusted odds ratio (OR) = 5.55 and OR = 3.60, respectively). The impact of family affluence was revealed only in interaction with other factors. Patterns of substance use in mid-adolescence are strongly related to perceived academic achievements, and these interact with selected socio-demographic factors. PMID:28009806
The rise of new psychoactive substance use in Australia.

PubMed

Burns, Lucy; Roxburgh, Amanda; Matthews, Allison; Bruno, Raimondo; Lenton, Simon; Van Buskirk, Joe

2014-01-01

New Psychoactive Substances are now a feature of Australia's recreational drug market. Little is known, however, about the prevalence of use, the characteristics of people who use them and the relationship between the NPS and ecstasy markets. This study examined the prevalence and correlates of NPS use amongst a group of regular ecstasy users in Australia. Participants were recruited if they had used ecstasy at least six times in the previous six months, lived in a capital city and were over 16 years of age. Purposive sampling was used, recruiting through universities and colleges, word of mouth and street press. 654 participants were recruited in 2013. Respondents who had used an NPS in the past six months were compared to those who had not. NPS were used by 44% of the total sample. In 2013 2C-I (14%) and 2C-B (8%) were the most prevalent NPS. Respondents in the NPS group were younger and reported more frequent use of more types of drugs. They were also more likely to rate the purity of ecstasy as low relative to those in the no NPS group. NPS are now an established part of Australia's recreational drug scene and NPS with hallucinogenic effects are now used most commonly. Monitoring systems need to develop capacity to monitor this highly dynamic market. Copyright © 2014 John Wiley & Sons, Ltd.
[Synthetic cannabinoids: A new addiction matrix].

PubMed

Scocard, Amandine; Benyamina, Amine; Coscas, Sarah; Karila, Laurent

2017-01-01

Synthetic cannabinoids (SC) belong to the emergent market of new psychoactive substances, sold on the Internet or specialized shops. Since the 1970s, more than 160 new SC have invaded the drug market. These substances imitate the psychoactive effects of cannabis. Underestimated for too long, SC's market growth and consequences are no longer to be ignored, first of all in terms of public health. SC were first synthesized during researches on the endocannabinoid system. Though they are agonists of the cannabinoid receptors 1 and 2, as Δ9-tetrahydrocannabinol in cannabis, they can also have a really high affinity with these receptors, rising up their potency. Each country in the world has chosen various ways how to deal with SC: scheduling, blanket ban, regulation… In order to contour the legal system, producers regularly modify the chemical formulas of those substances and hand out an attracting packaging looking harmless. However, the content of those small packets is extremely unstable and unreliable, including harmful compounds to health. Reports show an increasing number of non-fatal intoxications but also fatalities. Consequences on the body are numerous but there have been also reports of mental health imbalance and appearances of addiction-linked clinical signs. This review of literature aims at establishing a picture on SC in order to raise awareness among professionals in the health field on this new addiction matrix. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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