Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance.

PubMed

Dinis-Oliveira, Ricardo Jorge

2017-02-01

Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) 2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

[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.

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.

[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.

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.

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

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.

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.

"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.

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.

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.

Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities.

PubMed

Stebelska, Katarzyna

2013-08-01

Psychoactive drugs of fungal origin, psilocin, ibotenic acid, and muscimol among them have been proposed for recreational use and popularized since the 1960s, XX century. Despite their well-documented neurotoxicity, they reached reputation of being safe and nonaddictive. Scientific efforts to find any medical application for these hallucinogens in psychiatry, psychotherapy, and even for religious rituals support are highly controversial. Even if they show any healing potential, their usage in psychotherapy is in some cases inadequate and may additionally harm seriously suffering patients. Hallucinogens are thought to reduce cognitive functions. However, in case of indolealkylamines, such as psilocin, some recent findings suggest their ability to improve perception and mental skills, what would motivate the consumption of "magic mushrooms." The present article offers an opportunity to find out what are the main symptoms of intoxication with mushrooms containing psilocybin/psilocin, muscimol, and ibotenic acid. The progress in analytical methods for detection of them in fungal material, food, and body fluids is reviewed. Findings on the mechanisms of their biologic activity are summarized. Additionally, therapeutic potential of these fungal psychoactive compounds and health risk associated with their abuse are discussed.

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.

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.

First systematic evaluation of the potency of Cannabis sativa plants grown in Albania.

PubMed

Bruci, Zana; Papoutsis, Ioannis; Athanaselis, Sotirios; Nikolaou, Panagiota; Pazari, Ermira; Spiliopoulou, Chara; Vyshka, Gentian

2012-10-10

Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS.

PubMed

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

2017-02-01

Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MS n , or LC-HR-MS/MS. Aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations could be proposed for all compounds as main pathways. Carboxylation after initial hydroxylation of the methyl group could also be detected for 7-Me-DALT and O-demethylenation was observed for 5,6-MD-DALT. All phase I metabolites were extensively glucuronidated or sulfated. Initial phase I reactions were catalyzed by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. Rat urine samples were analyzed following two different low-dose administrations. GC-MS was not able to monitor consumption reliably, but all three compounds are predicted to be detectable in cases of overdose. The LC-MS n and LC-HR-MS/MS approaches were suitable for detecting an intake of all three compounds mainly via their metabolites. However, after the lowest dose, a reliable monitoring could only be achieved for 5-F-DALT via LC-MS n and LC-HR-MS/MS and for 7-Me-DALT via LC-HR-MS/MS. The most abundant targets in both LC-MS screenings were one of two hydroxy-aryl metabolites and both corresponding glucuronides for 5-F-DALT, one N-deallyl hydroxy-aryl, the carboxy, and one dihydroxy-aryl metabolite for 7-Me-DALT, and the demethylenyl metabolite, its oxo metabolite, and glucuronide for 5,6-MD-DALT.

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).

'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.

In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS.

PubMed

Boumrah, Yacine; Humbert, Luc; Phanithavong, Melodie; Khimeche, Kamel; Dahmani, Abdallah; Allorge, Delphine

2016-02-01

One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false-negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP- and UGT-dependent metabolites of the 2-(4-bromo-2,5-dimethoxy-phenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra-high performance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry detector (UHPLC-Q-TOF/MS). On-line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified. O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B-NBOMe and allow us to detect 25B-MBOMe users. Copyright © 2015 John Wiley & Sons, Ltd.

Structural elucidation and identification of a new derivative of phenethylamine using quadrupole time-of-flight mass spectrometry.

PubMed

Sekuła, Karolina; Zuba, Dariusz

2013-09-30

In recent years, the phenomenon of uncontrolled distribution of new psychoactive substances that were marketed without prior toxicological studies has been observed. Because many designer drugs are related in chemical structure, the potential for misidentifying them is an important problem. It is therefore essential to develop an analytical procedure for unequivocal elucidation of the structures of these compounds. The issue has been discussed in the context of 25I-NBMD [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2,3-methylenedioxyphenyl)methyl]ethanamine], a psychoactive substance first discovered on the drug market in 2012. The substance was extracted from blotter papers with methanol. Separation was achieved via liquid chromatography. Analysis was conducted by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). Identification of the psychoactive component was supported by electron impact gas chromatography/mass spectrometry (GC/EI-MS). The high accuracy of the LC/ESI-QTOFMS method allowed the molecular mass of the investigated substance (M(exp) = 441.0438 Da; mass error, ∆m = 0.2 ppm) and the formulae of ions formed during fragmentation to be determined. The main ions were recorded at m/z = 135.0440, 290.9876 and 305.9981. Structures of the obtained ions were elucidated in the tandem mass spectrometry (MS/MS) experiments by comparing them to mass spectra of previously detected derivatives of phenethylamine. The performed study indicated the potential for using LC/QTOFMS method to identify new designer drugs. This technique can be used supplementary to standard GC/MS. Prior knowledge of the fragmentation mechanisms of phenethylamines allowed to predict the mass spectra of the novel substance--25I-NBMD. Copyright © 2013 John Wiley & Sons, Ltd.

[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.

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.

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.

[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.

Analysis of a new drug of abuse: cathinone derivative 1-(3,4-dimethoxyphenyl)-2-(ethylamino)pentan-1-one.

PubMed

Weiß, Jennifer A; Taschwer, Magdalena; Kunert, Olaf; Schmid, Martin G

2015-03-01

Recently, novel psychoactive drugs for human abuse such as amphetamines, phenethylamines, benzofuries, and tryptamines, cathinones have gained high popularity. These designer drugs are mainly sold via online stores as "bath salts" and are labeled "not for human consumption." Due to the novelty of the compounds, only a little information about pharmacology, toxicology, and the long-term damage they may cause is available. Moreover, there are only few analytical methods for their identification and analysis. Among new cathinone derivatives, 1-(3,4-dimethoxyphenyl)-2-(ethylamino)pentan-1-one (DL-4662), became available via an internet shop. A sample of this compound was purchased and investigated. The first aim of our study was an identity check by NMR spectroscopy and gas chromatography with mass spectrometry. As many of the recreational drugs are chiral and are mainly sold as racemates, a further goal of our research was enantioseparation by gas chromatography with mass spectrometry and high-performance liquid chromatography with UV detection, to prove whether DL-4662 was traded enantiomerically pure or as racemic mixture. Both chiral separation methods showed the presence of a racemate. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Cannabis in sport: anti-doping perspective.

PubMed

Huestis, Marilyn A; Mazzoni, Irene; Rabin, Olivier

2011-11-01

Since 2004, when the World Anti-Doping Agency assumed the responsibility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of cannabis to enhance sports performance, the risk it poses to the athlete's health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Δ(9)-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology.

Cannabis in Sport

PubMed Central

Huestis, Marilyn A.; Mazzoni, Irene; Rabin, Olivier

2013-01-01

Since 2004, when the World Anti-Doping Agency assumed the responsi-bility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of can-nabis to enhance sports performance, the risk it poses to the athlete’s health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Δ9-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology. PMID:21985215

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.

The Toxicology of New Psychoactive Substances: Synthetic Cathinones and Phenylethylamines.

PubMed

Tyrkkö, Elli; Andersson, Mikael; Kronstrand, Robert

2016-04-01

New psychoactive substances (NPSs) are substitutes for classical drugs of abuse and there are now compounds available from all groups of classical drugs of abuse. During 2014, the number of synthetic cathinones increased dramatically and, together with phenylethylamines, they dominate the NPS markets in the European Union. In total, 31 cathinones and 9 phenylethylamines were encountered in 2014. The aim of this article was to summarize the existing knowledge about the basic pharmacology, metabolism, and human toxicology of relevant synthetic cathinones and phenylethylamines. Compared with existing reviews, we have also compiled the existing case reports from both fatal and nonfatal intoxications. We performed a comprehensive literature search using bibliographic databases PubMed and Web of Science, complemented with Google Scholar. The focus of the literature search was on original articles, case reports, and previously published review articles published in 2014 or earlier. The rapid increase of NPSs is a growing concern and sets new challenges not only for societies in drug prevention and legislation but also in clinical and forensic toxicology. In vivo and in vitro studies have demonstrated that the pharmacodynamic profile of cathinones is similar to that of other psychomotor stimulants. Metabolism studies show that cathinones and phenylethylamines are extensively metabolized; however, the parent compound is usually detectable in human urine. In vitro studies have shown that many cathinones and phenylethylamines are metabolized by CYP2D6 enzymes. This indicates that these drugs may have many possible drug-drug interactions and that genetic polymorphism may influence their toxicity. However, the clinical and toxicological relevance of CYP2D6 in adverse effects of cathinones and phenylethylamines is questionable, because these compounds are metabolized by other enzymes as well. The toxidromes commonly encountered after ingestion of cathinones and phenylethylamines are mainly of sympathomimetic and hallucinogenic character with a risk of excited delirium and life-threatening cardiovascular effects. The acute and chronic toxicity of many NPSs is unknown or very sparsely investigated. There is a need for evidence-based-treatment recommendations for acute intoxications and a demand for new strategies to analyze these compounds in clinical and forensic cases.

[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.

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.

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.

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

Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

PubMed Central

Banks, Matthew L.; Negus, S. Stevens

2012-01-01

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures. PMID:23243420

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

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.

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.

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 ").

[Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard].

PubMed

Bonnet, U; Mahler, H

2015-04-01

Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e. g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e. g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs. © Georg Thieme Verlag KG Stuttgart · New York.

Medicinal Plants Used for Neuropsychiatric Disorders Treatment in the Hauts Bassins Region of Burkina Faso

PubMed Central

Kinda, Prosper T.; Zerbo, Patrice; Guenné, Samson; Compaoré, Moussa; Ciobica, Alin; Kiendrebeogo, Martin

2017-01-01

Background: In Burkina Faso, phytotherapy is the main medical alternative used by populations to manage various diseases that affect the nervous system. The aim of the present study was to report medicinal plants with psychoactive properties used to treat neuropsychiatric disorders in the Hauts Bassins region, in the western zone of Burkina Faso. Methods: Through an ethnobotanical survey using structured questionnaire, 53 traditional healers (TH) were interviewed about neuropsychiatric disorders, medicinal plants and medical practices used to treat them. The survey was carried out over a period of three months. Results: The results report 66 plant species used to treat neuropsychiatric pathologies. Roots (36.2%) and leaves (29%) were the main plant parts used. Alone or associated, these parts were used to prepare drugs using mainly the decoction and the trituration methods. Remedies were administered via drink, fumigation and external applications. Conclusions: It appears from this study a real knowledge of neuropsychiatric disorders in the traditional medicine of Hauts Bassins area. The therapeutic remedies suggested in this work are a real interest in the fight against psychiatric and neurological diseases. In the future, identified plants could be used for searching antipsychotic or neuroprotective compounds. PMID:28930246

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

Simple and rapid screening procedure for 143 new psychoactive substances by liquid chromatography-tandem mass spectrometry.

PubMed

Adamowicz, Piotr; Tokarczyk, Bogdan

2016-07-01

In recent years, many new psychoactive substances (NPS) from several drug classes have appeared on the drug market. These substances, also known as 'legal highs', belong to different chemical classes. Despite the increasing number of NPS, there are few comprehensive screening methods for their detection in biological specimens. In this context, the purpose of this study was to develop a fast and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening procedure for NPS in blood. The elaborated method allows the simultaneous screening of 143 compounds from different groups (number of compounds): cathinones (36), phenethylamines (26), tryptamines (18), piperazines (9), piperidines (2), synthetic cannabinoids (34), arylalkylamines (7), arylcyclohexylamines (3), aminoindanes (2), and other drugs (6). Blood samples (0.2 mL) were precipitated with acetonitrile (0.6 mL). The separation was achieved with gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water in 14 min. Detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The total number of transitions monitored in dynamic mode was 432. The whole procedure was rapid and simple. The limits of detection (LODs) estimated for 104 compounds were in the range 0.01-3.09 ng/mL. The extraction recoveries determined for 32 compounds were from 1.8 to 133%. The procedure was successfully applied to the analysis of forensic blood samples in routine casework. The developed method should have wide applicability for rapid screening of new drugs of abuse in forensic or clinical samples. The procedure can be easily expanded for more substances. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Anxiolytic-like effects of noribogaine in zebrafish.

PubMed

Kalueff, Allan V; Kaluyeva, Aleksandra; Maillet, Emeline L

2017-07-14

Noribogaine is the main psychoactive metabolite of the hallucinogenic drug ibogaine, and is a particularly interesting compound potentially useful to treat dependence and various psychiatric disorders. Here, we report the effects of noribogaine on anxiety and locomotion in zebrafish (Danio rerio), a new promising model organism in neurobehavioral and psychopharmacological research. Adult zebrafish were subjected to the 5min novel tank test (NTT) following an acute, 20-min drug immersion in 1, 5 and 10mg/L noribogaine. Overall, noribogaine produced robust anxiolytic-like behavior in zebrafish (increasing the time spent and transitions to the top half compartment and reducing freezing bouts) without overt effects on fish locomotion. Taken together, these results indicate that noribogaine modulates the components of the acute stress response related to emotionality and anxiety behaviors, implicating this drug as a potentially useful non-sedative anxiolytic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Isolation and characterization of yuremamine, a new phytoindole.

PubMed

Vepsäläinen, Jouko J; Auriola, Seppo; Tukiainen, Mikko; Ropponen, Nina; Callaway, J C

2005-11-01

Yuremamine was isolated and characterized from the stem bark of Mimosa tenuiflora. This plant is still used by indigenous peoples in North-eastern Brazil to make yurema, a psychoactive beverage that is used for medico-religious purpose ( jurema preta or vinho da jurema, in Portuguese). The characterization of this novel compound by NMR and mass spectrometry introduces a new class of phytoindoles.

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.

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.

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.

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

PubMed

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-10-01

The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer

PubMed Central

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-01-01

Background and Purpose The psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. Experimental Approach To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. Key Results CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. Conclusions and Implications O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. PMID:24910342

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.

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.

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.

[Speed drugs].

PubMed

Piekoszewski, Wojciech; Florek, Ewa

2009-01-01

Until recently "speed drugs" have not awake higher social emotions. Usually they associate with Red Bull, allowed driving long time, and workaholic from modern enterprise to regenerate before next task. Currently on the base of new regulation on the list of controlled substances benzylpyperazine, its related compounds and 17 plants products were added. The article discussed the sources and biological action of these psychoactive substances, which are illegal in Poland.

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

Spiritual and ceremonial plants in North America: an assessment of Moerman's ethnobotanical database comparing Residual, Binomial, Bayesian and Imprecise Dirichlet Model (IDM) analysis.

PubMed

Turi, Christina E; Murch, Susan J

2013-07-09

Ethnobotanical research and the study of plants used for rituals, ceremonies and to connect with the spirit world have led to the discovery of many novel psychoactive compounds such as nicotine, caffeine, and cocaine. In North America, spiritual and ceremonial uses of plants are well documented and can be accessed online via the University of Michigan's Native American Ethnobotany Database. The objective of the study was to compare Residual, Bayesian, Binomial and Imprecise Dirichlet Model (IDM) analyses of ritual, ceremonial and spiritual plants in Moerman's ethnobotanical database and to identify genera that may be good candidates for the discovery of novel psychoactive compounds. The database was queried with the following format "Family Name AND Ceremonial OR Spiritual" for 263 North American botanical families. Spiritual and ceremonial flora consisted of 86 families with 517 species belonging to 292 genera. Spiritual taxa were then grouped further into ceremonial medicines and items categories. Residual, Bayesian, Binomial and IDM analysis were performed to identify over and under-utilized families. The 4 statistical approaches were in good agreement when identifying under-utilized families but large families (>393 species) were underemphasized by Binomial, Bayesian and IDM approaches for over-utilization. Residual, Binomial, and IDM analysis identified similar families as over-utilized in the medium (92-392 species) and small (<92 species) classes. The families Apiaceae, Asteraceae, Ericacea, Pinaceae and Salicaceae were identified as significantly over-utilized as ceremonial medicines in medium and large sized families. Analysis of genera within the Apiaceae and Asteraceae suggest that the genus Ligusticum and Artemisia are good candidates for facilitating the discovery of novel psychoactive compounds. The 4 statistical approaches were not consistent in the selection of over-utilization of flora. Residual analysis revealed overall trends that were supported by Binomial analysis when separated into small, medium and large families. The Bayesian, Binomial and IDM approaches identified different genera as potentially important. Species belonging to the genus Artemisia and Ligusticum were most consistently identified and may be valuable in future studies of the ethnopharmacology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

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.

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

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.

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.

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.

Mind navigators of chemicals' experimenters? A web-based description of e-psychonauts.

PubMed

Orsolini, Laura; Papanti, Gabriele Duccio; Francesconi, Giulia; Schifano, Fabrizio

2015-05-01

Within online drug fora communities, there are some "educated and informed" users who can somehow provide reliable information on psychoactive compounds and combinations. These users, also called "e-psychonauts," may possess levels of technical knowledge relating to a range of novel psychoactive substances (NPS). The present project aimed at identifying and describing the e-psychonauts' socio-demographic characteristics and their motivations and patterns of drug intake. A netnographic research methodology, carried out through an unobtrusive observational approach of a list of cyber drug communities (blogs, fora, Facebook, and Twitter pages) was carried out. The fora posts and threads were accurately reviewed, analyzed, and compared using the empirical phenomenological psychological (EPP) method. Data were collected between January and February 2014. Psychonauts typically considered themselves as "psychedelic researchers," "new Shamans," "philosophers," or "alchemists." They appeared to be mainly young, males, unmarried, and Caucasians. They presented with good or excellent employment conditions and with a set of key skills, including attention to their inner "soul"; high standards of knowledge about drugs' chemical and pharmacological issues; and high levels of both IT skills and verbal fluency in reporting their own "on drug" experiences. The e-psychonauts seemed to "test" and at times synthesize a range of drugs to achieve the state of consciousness they find most pleasurable. There is the need to improve both the existing levels of professionals' knowledge on this novel generation of drug misusers and to design and develop novel prevention approaches that are able to attract the attention of the e-psychonauts.

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,…

Occurrence and distribution of psychoactive compounds and their metabolites in the urban water cycle of Berlin (Germany).

PubMed

Hass, Ulrike; Duennbier, Uwe; Massmann, Gudrun

2012-11-15

The occurrence and distribution of six psychoactive compounds (primidone, phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a metabolite of primidone (phenylethylmalonamide) were investigated in wastewater treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration site, raw and final drinking water, and in groundwater affected by former sewage irrigation. Primidone and its metabolite phenylethylmalonamide were found to be ubiquitous in environmental water samples in Berlin. Maximum concentrations of 0.87 and 0.42 μg/L, respectively, were encountered in WWTP effluents. Both compounds are apparently not removed when passaging through the different compartments of the water cycle and concentrations are only reduced by dilution. Phenobarbital was present at nearly every stage of the Berlin water cycle with the exception of raw and final drinking water. The highest concentrations of phenobarbital (up to 0.96 μg/L) were measured in groundwater influenced by former sewage irrigation. Oxazepam was only present in WWTP effluents and surface waters (up to 0.18 μg/L), while diazepam was not detected in any matrix. Due to their withdrawal from the German market years ago, the pharmaceuticals meprobamate and pyrithyldione were only found in sewage farm groundwater (up to 0.50 and 0.04 μg/L, respectively) and, in case of meprobamate, also in decade old bank filtrate (0.03 μg/L). Our results indicate a high persistence of some of the investigated compounds in the aquatic system. As a consequence, these pollutants may potentially reach drinking water resources via bank filtration if present in WWTP effluents and/or surface waters in partly closed water cycles such as Berlin's. Copyright © 2012 Elsevier Ltd. All rights reserved.

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

PubMed

Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

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.

[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).

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.

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

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.

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.

[Combination of hemodialysis and hemofiltration in severe caffeine intoxication].

PubMed

Colin-Benoit, Eugénie; Friolet, Raymond; Rusca, Marco; Teta, Daniel; Gobin, Niels

2017-05-01

A 21-year-old man ingested 75g of pure caffeine, in an attempt to commit suicide. This represents 7.5 times the minimal lethal dose. Caffeine, 1,3,7-trimethylxanthine, is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet. Mechanisms of action are dose-dependent. When caffeine overdosing occurs, neurologic, cardiovascular and renal systems are mainly affected. Severe intoxication can be fatal. No antidote is available and treatment is purely symptomatic. Hemoperfusion has previously been carried out in the 1990's to treat patients with caffeine intoxication. Since 2009, hemodialysis and hemofiltration have proposed as well. Our patient was successfully treated with a combination of hemodiafiltration, intermittent and then continuous. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Historical and cultural aspects of man's relationship with addictive drugs

PubMed Central

Crocq, Marc-Antoine

2007-01-01

Our taste for addictive psychoactive substances is attested to in the earliest human records. Historically, psychoactive substances have been used by (i) priests in religious ceremonies (eg, amanita muscaria); (ii) healers for medicinal purposes (eg, opium); or (iii) the general population in a socially approved way (eg, alcohol, nicotine, and caffeine). Our forebears refined more potent compounds and devised faster routes of administration, which contributed to abuse. Pathological use was described as early as classical Antiquity. The issue of loss of control of the substance, heralding today's concept of addiction, was already being discussed in the 17th century. The complex etiology of addiction is reflected in the frequent pendulum swings between opposing attitudes on issues that are still currently being debated, such as: is addiction a sin or a disease; should treatment be moral or medical; is addiction caused by the substance; the individual's vulnerability and psychology, or social factors; should substances be regulated or freely available. PMID:18286796

New psychoactive substances: an overview on recent publications on their toxicodynamics and toxicokinetics.

PubMed

Meyer, Markus R

2016-10-01

This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies. Both sections are then concluded by an opinion on these latest developments. This review shows that the NPS market is still highly dynamic and that the data published on their toxicodynamics and toxicokinetics can hardly keep pace with the appearance of new entities. However, data available are very helpful to understand and predict how NPS may behave in severe intoxication. The currently best-documented parameter is the in vitro metabolism of NPS, a prerequisite to allow detection of NPS in biological matrices in cases of acute intoxications or chronic consumption. However, additional data such as their chronic toxicity are still lacking.

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

[Psilocybin - public available psychodysleptic].

PubMed

Dydak, Karolina; Śliwińska-Mossoń, Mariola; Milnerowicz, Halina

2015-09-07

Substances of plant origin have been used to induce hallucinations for a long time, in religious ceremonies and rituals as well as in pain relief. Psilocybin and psilocin naturally occur in the fungal genus Psilocybe. Due to the psychedelic effects and relative harmlessness of these substances and the fact that they do not cause physical addiction, psilocybin and psilocin recently have been increasingly replacing synthetic psychodysleptics, such as diethylamide D-lysergic acid. Both compounds as psychoactive substances are illegal, but psilocybin, in addition to psychotropic action, also shows positive effects, which from a medical point of view indicate its therapeutic potential and capacity for use in therapy. However, poisoning by psilocin and its derivatives is still a major clinical and social problem, mainly among young people, which is why quick and reliable identification of these substances is very important. Traditional ways of assigning the sample to a particular taxon, such as morphological and biochemical analysis or palynological and sporological studies, are not very universal and often do not provide clear results. Credibility, high speed and lower cost of DNA analysis make genetic methods more often used to determine the species of fungi. These methods are random amplification of polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP) and high resolution melting (HRM). Moreover, analysis of the regions ITS1 and nLSU was suggested as a valid method for application in the molecular taxonomy of fungi for forensic purposes. Modern methods of identifying psilocybin and psilocin in fungi and biological material are: zone capillary electrophoresis, high performance liquid chromatography, gas chromatography and liquid chromatography coupled with mass spectrometry. The mentioned methods are successfully used for the identification of psychoactive substances in fungi as well as in blood and urine samples.

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.

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

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.

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.

"Legal highs": safe and legal "heavens"? A study on the diffusion, knowledge and risk awareness of novel psychoactive drugs among students in the UK.

PubMed

Corazza, Ornella; Simonato, Pierluigi; Corkery, John; Trincas, Giuseppina; Schifano, Fabrizio

2014-01-01

The recent emergence of new recreational drugs, combined with the ability of the Internet to disseminate information quickly, have raised a number of concerns in the fields of drug policy, substance use research, and public health. A semi-structured questionnaire was advertised on The Study Room's website from November to December 2010 to explore the awareness, the use and the perception of risks of "legal highs" among student population in the UK. One-third (31.40%) of the 446 participants reported use of these kinds of drugs. Respondents were more likely to have taken were: mephedrone (41.4%), Salvia divinorum (20%), "Spice drugs" (10.7%), methylone (1.4%), naphyrone (NRG) (2.1%) and benzylpiperazine (BZP) (2.1%), while 15.7% did not know what compounds they had ever consumed. The large majority (78.9%) considered these as legal substances, while 74.2% did not consider these safer than illicit drugs. Half (50.8%) of the respondents were aware of the presence of illegal agents in the products they had consumed. The study contributes to an initial assessment of the use and the risks awareness of novel psychoactive compounds among students in the UK. Further research is required, especially in terms of personality and lifestyle attitudes to better profile these new forms of abuse also in non-recreational settings.

Recreational use of 1-(2-naphthyl)-2-(1-pyrrolidinyl)-1-pentanone hydrochloride (NRG-1), 6-(2-aminopropyl) benzofuran (benzofury/ 6-APB) and NRG-2 with review of available evidence-based literature.

PubMed

Jebadurai, Jeshoor; Schifano, Fabrizio; Deluca, Paolo

2013-07-01

This study aimed to review the available evidence-based literature on novel psychoactive substances and to inform health care professionals. Internet searches were carried out using Google and Yahoo by using specific key words. For each set of key words, the first 100 websites identified by Google and Yahoo were fully assessed, together with a further 5% of random samples selected by research randomizer of the remaining websites. Thus, a list of unique web forums was identified, and qualitative information was extracted. Available evidence-based literature were reviewed along with a user's experimentation with mephedrone, NRG-1, NRG-2 and Benzofury. It showed that when a substance (mephedrone) became controlled, the vendors aggressively promote the sale of other new compounds (NRG-1, NRG-2, Benzofury) to attract vulnerable adults. The characteristics, toxicity and suggested management of these new compounds (NRG-1, NRG-2, Benzofury) are discussed. The arrival of hundreds of novel psychoactive substances for sale online has raised a number of public health and legal issues. Although evidence-based literature remains limited, few studies identified that most products do not contain the ingredients as advertised. Better levels of international cooperation and rapid share of available information may be needed to tackle this emerging problem. Copyright © 2013 John Wiley & Sons, Ltd.

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.

[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.

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.

Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn , and LC-HR-MS/MS.

PubMed

Caspar, Achim T; Gaab, Jonas B; Michely, Julian A; Brandt, Simon D; Meyer, Markus R; Maurer, Hans H

2018-01-01

Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MS n ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MS n , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

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.

Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

PubMed

Swedberg, Michael D B

2016-01-01

Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit clear discriminative effects when tested against classical drugs of abuse in drug discrimination studies, and were not self-administered by rats. However, these compounds did cause salient discriminative effects of their own in animals trained to discriminate them from no drug. Therefore, from a safety pharmacology perspective, novel compounds that do not cause discriminative effects similar to classical drugs of abuse, may still cause psychoactive effects in humans and carry the potential to maintain drug abuse, suggesting that proactive investigation of drug abuse potential is warranted (Swedberg, 2013). These and other findings will be discussed, and the application of drug discrimination procedures beyond the typical standard application of testing novel compounds against known and well characterized reference drugs will be addressed. Copyright © 2016 Elsevier Inc. 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.

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.

Sorption behavior of 20 wastewater originated micropollutants in groundwater — Column experiments with pharmaceutical residues and industrial agents

NASA Astrophysics Data System (ADS)

Burke, Victoria; Treumann, Svantje; Duennbier, Uwe; Greskowiak, Janek; Massmann, Gudrun

2013-11-01

Since sorption is an essential process with regard to attenuation of organic pollutants during subsurface flow, information on the sorption properties of each pollutant are essential for assessing their environmental fate and transport behavior. In the present study, the sorption behavior of 20 wastewater originated organic micropollutants was assessed by means of sediment column experiments, since experimentally determined data for these compounds are not or sparsely represented in the literature. Compounds investigated include various psychoactive drugs, phenazone-type pharmaceuticals and β-blockers, as well as phenacetine, N-methylphenacetine, tolyltriazole and para-toluenesulfonamide. While for most of the compounds no or only a low sorption affinity was observed, an elevated tendency to sorb onto aquifer sand was obtained for the β-blockers atenolol, propranolol and metoprolol. A comparison between experimental data and data estimated based on the octanol/water partition coefficient following the QSAR approach demonstrated the limitations of the latter to predict the adsorption behavior in natural systems for the studied compounds.

Sorption behavior of 20 wastewater originated micropollutants in groundwater--column experiments with pharmaceutical residues and industrial agents.

PubMed

Burke, Victoria; Treumann, Svantje; Duennbier, Uwe; Greskowiak, Janek; Massmann, Gudrun

2013-11-01

Since sorption is an essential process with regard to attenuation of organic pollutants during subsurface flow, information on the sorption properties of each pollutant are essential for assessing their environmental fate and transport behavior. In the present study, the sorption behavior of 20 wastewater originated organic micropollutants was assessed by means of sediment column experiments, since experimentally determined data for these compounds are not or sparsely represented in the literature. Compounds investigated include various psychoactive drugs, phenazone-type pharmaceuticals and β-blockers, as well as phenacetine, N-methylphenacetine, tolyltriazole and para-toluenesulfonamide. While for most of the compounds no or only a low sorption affinity was observed, an elevated tendency to sorb onto aquifer sand was obtained for the β-blockers atenolol, propranolol and metoprolol. A comparison between experimental data and data estimated based on the octanol/water partition coefficient following the QSAR approach demonstrated the limitations of the latter to predict the adsorption behavior in natural systems for the studied compounds. © 2013.

Evolutionary Considerations on the Emerging Subculture of the E-psychonauts and the Novel Psychoactive Substances: A Comeback to the Shamanism?

PubMed

Orsolini, Laura; St John-Smith, Paul; McQueen, Daniel; Papanti, Duccio; Corkery, John; Schifano, Fabrizio

2017-01-01

Evolutionary research on drug abuse has hitherto been restricted to proximate studies, considering aetiology, mechanism, and ontogeny. However, in order to explain the recent emergency of a new behavioral pattern (e.g. 'the e-psychonaut style') of novel psychoactive substances' (NPS) intake, a complementary evolutionary model may be needed. A range of evolutionary interpretations on the 'psychonaut style' and the recent emergency of NPS were here considered. The PubMed database was searched in order to elicit evolutionary theory-based documents commenting on NPS/NPS users/e-psychonauts. The traditional 'shamanic style' use of entheogens/plant-derived compounds may present with a range of similarities with the 'e-psychonauts' use of mostly of hallucinogen/psychedelic NPS. These users consider themselves as 'new/technological' shamans. Indeed, a range of evolutionary mechanisms, such as: optimal foraging, costly signaling, and reproduction at the expense of health may all cooperate to explain the recent spread and diffusion of the NPS market, and this may represent a reason of concern. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

A data-independent acquisition workflow for qualitative screening of new psychoactive substances in biological samples.

PubMed

Kinyua, Juliet; Negreira, Noelia; Ibáñez, María; Bijlsma, Lubertus; Hernández, Félix; Covaci, Adrian; van Nuijs, Alexander L N

2015-11-01

Identification of new psychoactive substances (NPS) is challenging. Developing targeted methods for their analysis can be difficult and costly due to their impermanence on the drug scene. Accurate-mass mass spectrometry (AMMS) using a quadrupole time-of-flight (QTOF) analyzer can be useful for wide-scope screening since it provides sensitive, full-spectrum MS data. Our article presents a qualitative screening workflow based on data-independent acquisition mode (all-ions MS/MS) on liquid chromatography (LC) coupled to QTOFMS for the detection and identification of NPS in biological matrices. The workflow combines and structures fundamentals of target and suspect screening data processing techniques in a structured algorithm. This allows the detection and tentative identification of NPS and their metabolites. We have applied the workflow to two actual case studies involving drug intoxications where we detected and confirmed the parent compounds ketamine, 25B-NBOMe, 25C-NBOMe, and several predicted phase I and II metabolites not previously reported in urine and serum samples. The screening workflow demonstrates the added value for the detection and identification of NPS in biological matrices.

Evolutionary Considerations on the Emerging Subculture of the E-psychonauts and the Novel Psychoactive Substances: A Comeback to the Shamanism?

PubMed Central

Orsolini, Laura; St John-Smith, Paul; McQueen, Daniel; Papanti, Duccio; Corkery, John; Schifano, Fabrizio

2017-01-01

Background: Evolutionary research on drug abuse has hitherto been restricted to proximate studies, considering aetiology, mechanism, and ontogeny. However, in order to explain the recent emergency of a new behavioral pattern (e.g. ‘the e-psychonaut style’) of novel psychoactive substances’ (NPS) intake, a complementary evolutionary model may be needed. Objective A range of evolutionary interpretations on the ‘psychonaut style’ and the recent emergency of NPS were here considered. Method The PubMed database was searched in order to elicit evolutionary theory-based documents commenting on NPS/NPS users/e-psychonauts. Results The traditional ‘shamanic style’ use of entheogens/plant-derived compounds may present with a range of similarities with the ‘e-psychonauts’ use of mostly of hallucinogen/psychedelic NPS. These users consider themselves as ‘new/technological’ shamans. Conclusion Indeed, a range of evolutionary mechanisms, such as: optimal foraging, costly signaling, and reproduction at the expense of health may all cooperate to explain the recent spread and diffusion of the NPS market, and this may represent a reason of concern. PMID:27834144

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.

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…

Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.

PubMed

Abouchedid, Rachelle; Ho, James H; Hudson, Simon; Dines, Alison; Archer, John R H; Wood, David M; Dargan, Paul I

2016-12-01

Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance. We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of "cannabis tea" and "mushroom tea") as well as two LSD blotters. After the "cannabis tea" was smoked and the two LSD blotters and "mushroom tea" were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20-30 beats) 1-2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression. To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.

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.

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.

Phytochemistry of Cannabis sativa L.

PubMed

ElSohly, Mahmoud A; Radwan, Mohamed M; Gul, Waseem; Chandra, Suman; Galal, Ahmed

Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ 9 -tetrahydrocannabinol (Δ 9 -THC). The plant's behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ 9 -THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ 9 -THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer's, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

A study of cannabis potency in France over a 25 years period (1992-2016).

PubMed

Dujourdy, Laurence; Besacier, Fabrice

2017-03-01

Cannabis contains a unique class of compounds known as the cannabinoids. Pharmacologically, the principal psychoactive constituent is Δ 9 -tetrahydrocannabinol (THC). The amount of THC in conjunction with selected additional cannabinoid compounds (cannabidiol/CBD, cannabinol/CBN), determines the strength or potency of the cannabis product. Recently, reports have speculated over the change in the quality of cannabis products, from nearly a decade, specifically concerning the increase in cannabinoid content. This article exploits the analytical data of cannabis samples analyzed in the five French forensic police laboratories over 25 years. The increase potency of both herbal and resin cannabis in France is proved through the monitoring of THC content. For cannabis resin, it has slowly risen from 1992 to 2009, before a considerable increase in the last four years (mean THC content in mid-2016 is 23% compared to 10% in 2009). For herbal cannabis, it has known three main stages of growth (mean THC content is 13% in 2015 and mid-2016 compared to 7% in 2009 and 2% in 1995). The calculation of THC/CBD ratios in both herbal and resin samples confirms the recent change in chemotypes in favor of high potency categories. Finally, the CBN/THC ratios in marijuana samples were measured in order to evaluate the freshness of French seized hemp. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The relevance of theobromine for the beneficial effects of cocoa consumption.

PubMed

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

2015-01-01

Cocoa consumption began in America and in the mid sixteenth Century it quickly spread to Europe. Beyond being considered a pleasant habit due to its rich sweet lingering taste, chocolate was considered a good nutrient and even a medicine. Traditionally, health benefits of cocoa have been related with the high content of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect due to methylxanthines in cocoa is notable. Theobromine and caffeine, in the proportions found in cocoa, are responsible for the liking of the food/beverage. These compounds influence in a positive way our moods and our state of alertness. Theobromine, which is found in higher amounts than caffeine, seems to be behind several effects attributed to cocoa intake. The main mechanisms of action are inhibition of phosphodiesterases and blockade of adenosine receptors. Further mechanisms are being explored to better understand the health benefits associated to theobromine consumption. Unlike what happens in other mammals -pets- included, theobromine is safe for humans and has fewer unwanted effects than caffeine. Therefore, theobromine deserves attention as one of the most attractive molecules in cocoa.

The relevance of theobromine for the beneficial effects of cocoa consumption

PubMed Central

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

2015-01-01

Cocoa consumption began in America and in the mid sixteenth Century it quickly spread to Europe. Beyond being considered a pleasant habit due to its rich sweet lingering taste, chocolate was considered a good nutrient and even a medicine. Traditionally, health benefits of cocoa have been related with the high content of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect due to methylxanthines in cocoa is notable. Theobromine and caffeine, in the proportions found in cocoa, are responsible for the liking of the food/beverage. These compounds influence in a positive way our moods and our state of alertness. Theobromine, which is found in higher amounts than caffeine, seems to be behind several effects attributed to cocoa intake. The main mechanisms of action are inhibition of phosphodiesterases and blockade of adenosine receptors. Further mechanisms are being explored to better understand the health benefits associated to theobromine consumption. Unlike what happens in other mammals -pets- included, theobromine is safe for humans and has fewer unwanted effects than caffeine. Therefore, theobromine deserves attention as one of the most attractive molecules in cocoa. PMID:25750625

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.

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.

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

Reversal of pentylenetetrazole-altered swimming and neural activity-regulated gene expression in zebrafish larvae by valproic acid and valerian extract.

PubMed

Torres-Hernández, Bianca A; Colón, Luis R; Rosa-Falero, Coral; Torrado, Aranza; Miscalichi, Nahira; Ortíz, José G; González-Sepúlveda, Lorena; Pérez-Ríos, Naydi; Suárez-Pérez, Erick; Bradsher, John N; Behra, Martine

2016-07-01

Ethnopharmacology has documented hundreds of psychoactive plants awaiting exploitation for drug discovery. A robust and inexpensive in vivo system allowing systematic screening would be critical to exploiting this knowledge. The objective of this study was to establish a cheap and accurate screening method which can be used for testing psychoactive efficacy of complex mixtures of unknown composition, like plant crude extracts. We used automated recording of zebrafish larval swimming behavior during light vs. dark periods which we reproducibly altered with an anxiogenic compound, pentylenetetrazole (PTZ). First, we reversed this PTZ-altered swimming by co-treatment with a well-defined synthetic anxiolytic drug, valproic acid (VPA). Next, we aimed at reversing it by adding crude root extracts of Valeriana officinalis (Val) from which VPA was originally derived. Finally, we assessed how expression of neural activity-regulated genes (c-fos, npas4a, and bdnf) known to be upregulated by PTZ treatment was affected in the presence of Val. Both VPA and Val significantly reversed the PTZ-altered swimming behaviors. Noticeably, Val at higher doses was affecting swimming independently of the presence of PTZ. A strong regulation of all three neural-activity genes was observed in Val-treated larvae which fully supported the behavioral results. We demonstrated in a combined behavioral-molecular approach the strong psychoactivity of a natural extract of unknown composition made from V. officinalis. Our results highlight the efficacy and sensitivity of such an approach, therefore offering a novel in vivo screening system amenable to high-throughput testing of promising ethnobotanical candidates.

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.

[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.

Illegal psychoactive substance consumption amongst older schoolchildren in the city of Tunja, Colombia.

PubMed

Ospina-Díaz, Juan M; Herrera-Amaya, Giomar M; Manrique-Abril, Fred G

2012-06-01

Assessing lifetime prevalence of illegal substance use and accessibility to such substances. Determining risk factors and the protective factors linked to them. This was a cross-sectional study using descriptive and bivariate analysis. A survey was applied to 1,515 students from 8th to 11th grades in the city's schools, ages ranging from 12 to 18. An increase in lifetime prevalence and lower age for consumption onset were found. The main risk factors were determined to be academic environment and attitudes towards school authorities, linked to recreational and sports groups without control by elders, gang membership and engaging in risky and dangerous activities. The results showed the need for a critical review of current promotion and prevention strategies aimed at controlling the use of psychoactive substances amongst children and adolescents, according to the current reality of trafficking and domestic consumption in Colombia.

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…

New psychoactive substances: Purchasing and supply patterns in Australia.

PubMed

Sutherland, Rachel; Bruno, Raimondo; Peacock, Amy; Dietze, Paul; Breen, Courtney; Burns, Lucinda; Barratt, Monica J

2017-05-01

To examine the purchasing and supply patterns of new psychoactive substance (NPS) consumers in Australia. Data were obtained from a self-selected sample of 296 past-year NPS consumers, with comparisons made across dimethyltryptamine (n = 104), 2C-x (n = 59), NBOMe (n = 27), and synthetic cannabinoid (n = 22) users. Most consumers (58%) nominated a friend as their main NPS source, and almost half (46%) reported that they had supplied NPS to others in the past year (predominantly "social supply"). However, when comparisons were made across NPS, NBOMe users were more likely to nominate a dealer (30%) or online marketplace (22%) as their main source and to report: supplying NPS to others (63%); supplying to strangers (29%) and acquaintances (24%); and supplying NPS for cash profit (29%). Similarly, NPS consumers who nominated online markets as their main NPS source (9%; n = 26) were more likely to have supplied NPS to others (risk ratio [RR] 1.57); supplied to strangers (RR 6.05) and acquaintances (RR 12.11); sold NPS for cash profit (RR 4.36); and to have exchanged NPS for something else (RR 3.27) than those who reported alternative primary sources. NBOMe consumers and those who nominated online markets as their main NPS source reported greater engagement with for-profit supply; it is unclear if these individuals have "drifted" into dealing or if they were already engaged in such activities. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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

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.

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.

[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.

New psychoactive substances in oral fluid of French and Belgian drivers in 2016.

PubMed

Richeval, Camille; Wille, Sarah Maria Richarda; Nachon-Phanithavong, Mélodie; Samyn, Nele; Allorge, Delphine; Gaulier, Jean-Michel

2018-04-06

Driving under the influence of drugs (DUID) is a worldwide problem with potentially major judiciary and life-threatening consequences. Up to now, only classical drugs of abuse (DOA) are tested for DUID detection. A challenging issue for drafting up-dated international drug policies is to take into account the recent and expanding new psychoactive substances (NPS) market. NPS consist in various narcotic or psychotropic drugs, most of them having a "legal" status, that replicate chemical structures and/or pharmacological effects of classical DOA. Although it is obvious that NPS can lead to impaired driving, the prevalence of NPS use in a DUID context is unknown since the applied roadside screening tests are not yet adapted for these compounds. Between January and December 2016, a total of 391 oral fluid specimens were obtained from used roadside immunochemical test devices for DOA (Drugwipe-5S ® device). These specimens were analyzed using liquid chromatography coupled with tandem mass spectrometry and high resolution mass spectrometry. NPS (mainly cathinone derivatives) were detected in 33 out of the 391 oral fluid samples. This NPS positivity rate of 8.4% in oral fluid of drivers who were submitted to a roadside drug testing in 2016 in France and in Belgium is comparable to the available blood data (NPS positivity rate of 7%) observed in 2015 in similar populations. Our results demonstrate the reality of driving after NPS use in French and Belgian drivers who were submitted to a roadside DOA test. As there is a lack of on-site detection methods to screen for NPS, the detection of NPS in a rapid and cost-effective DUID detection strategy is currently impossible. The expanding use of NPS, notably by drivers as reported here, and the inability of currently used drug detection tests, should be urgently addressed by road safety and law enforcement authorities. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

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.

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

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.

Legal highs: staying on top of the flood of novel psychoactive substances

PubMed Central

Baumeister, David; Tojo, Luis M.

2015-01-01

There has been growing clinical, public, and media awareness and concern about the availability and potential harmfulness of so-called ‘legal highs’, which are more appropriately called new or novel psychoactive substances (NPS). A cat-and-mouse process has emerged wherein unknown chemists and laboratories are producing new, and as yet nonproscribed, compounds for human consumption; and as soon as they are banned, which they inevitably are, slightly modified analogues are produced to circumvent new laws. This rapidly changing environment, 81 new substances were identified in 2013 alone, has led to confusion for clinicians, psychopharmacologists, and the public at large. Our difficulties in keeping up with the process has had a two-fold negative effect: the danger of ignoring what is confusing; and the problem that some of the newer synthesized compounds appear ever more potent. This review aims to circumscribe a quick moving and growing field, and to categorize NPS into five major groups based upon their ‘parent’ compounds: stimulants similar to cocaine, amphetamines and ecstasy; cannabinoids; benzodiazepine based drugs; dissociatives similar to ketamine and phencyclidine (PCP); and those modelled after classic hallucinogens such as LSD and psilocybin. Pharmacodynamic actions, subjective and physical effects, harmfulness, risk of dependency and, where appropriate, putative clinical potentials are described for each class. Clinicians might encounter NPS in various ways: anecdotal reportage; acute intoxication; as part of a substance misuse profile; and as a precipitant or perpetuating factor for longer-term physical and psychological ill health. Current data are overall limited, and much of our knowledge and treatment strategies are based upon those of the ‘parent’ compound. There is a critical need for more research in this field, and for professionals to make themselves more aware of this growing issue and how it might affect those we see clinically and try to help: a brave new world of so-called ‘psychonauts’ consuming NPS will also need informed ‘psychotherapeutonauts’. The paper should serve as a primer for clinicians and interested readers, as well as provide a framework into which to place the new substances that will inevitably be synthesized in the future. PMID:26240749

Public Experience with Psychoactive Substances: A Nationwide Study Among Adults and Youth. Part 1, Main Findings.

ERIC Educational Resources Information Center

Abelson, Herbert I.; Atkinson, Ronald B.

This is a study of beliefs, attitudes, and behavior with regard to a wide range of legal and illegal drugs. Included are data about coffee, tea, tobacco, and illicit drugs such as marihuana and heroin. The report covers the current situation and highlights trends from two prior studies on drug abuse conducted for the National Commission on…

Prescription and illicit psychoactive drugs in oral fluid--LC-MS/MS method development and analysis of samples from Brazilian drivers.

PubMed

Zancanaro, Ivomar; Limberger, Renata Pereira; Bohel, Paula O; dos Santos, Maíra Kerpel; De Boni, Raquel B; Pechansky, Flavio; Caldas, Eloisa Dutra

2012-11-30

This study is part of a larger project designed to investigate the prevalence of psychoactive drug (PAD) use among Brazilian drivers. In this paper we describe the development and validation of an analytical method to analyze 32 prescription and illicit PADs (amphetamines, benzodiazepines, cocaine, cannabis, opioids, ketamine and m-CPP) and metabolites in oral fluid samples collected with a Quantisal™ device. Samples were extracted with ethyl acetate:hexane and analyzed by LC-MS/MS. Instrumental LOD ranged from 0.26 to 0.65 ng/mL. Mean procedural recoveries at 1.3 ng/mL (LLOQ) ranged from 50% to 120% for 24 compounds. Recoveries were concentration independent, with the exception of femproporex, heroin and ecgonine methyl-ester (EME) for which the recovery decreased significantly at higher levels (13 and 52 ng/mL). RSD was <20% for all compounds at all spiking levels. Ion suppression due to the matrix was <20% for most compounds, and higher than 60% for EME and diethylpropion. Analysis was performed against a in-matrix standard curve. About 10% of the 2235 oral fluid samples collected from drivers on Brazilian Federal highways were positive (≥LOD) for at least one analyte investigated. Alone or in combination with other drugs, cocaine/metabolites were the analytes most detected in the samples (129; 5.8%), followed by amphetamines/metabolite (69; 3.1%), benzodiazepines (28; 1.2%), cannabinoids (23; 1.1%) and opioids (8; 0.4%). Detection of at least two PADs from different classes accounted for 9.3% of the 236 positive samples. Cocaine was found at higher levels in the samples (up to 1165 ng/mL). Preventive measures aimed at reducing the use of PADs by drivers in Brazil will certainly contribute to decrease the country's highway death rates. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

[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.

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.

Tetrahydrocannabinols in clinical and forensic toxicology.

PubMed

Kochanowski, Maciej; Kała, Maria

2005-01-01

Cannabinoids are the natural constituents of marihuana (cannabis). The main of them are delta9-tetrahydrocannabinol (9THC)--psychoactive agent, cannabinol (CBN) and cannabidiol (CBD). Cannabis is administered either by smoking or orally. 9THC potency and duration of action as well as its and two of its major metabolites concentrations in organism highly depend on the route of administration. A single active dose of 9THC is estimated on 520 mg. 9THC is rapidly metabolised. It is hydroxylated to an active metabolite, I1 -hydroxy-delta9-tetrahydro-cannabinol (11-OH-THC), then oxidised to an inactive 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), which is conjugated with glucuronic acid and predominantly excreted in the urine. The maximum psychological effect persists for 4-6 h after administration despite of very low 9THC blood concentrations. 9THC plasma concentration declined to values of 2-3 ng/ml during 3-4 h after smoking. Such a low concentration of the active compound in human organism create a demand for use of sensitive analytical methods for detection and determination of 9THC and its metabolites. The most effective techniques for 9THC and related compounds determination in biological material are chromatographic ones (gas and liquid) with mass spectrometric detection and different ionization modes. 9THC and its two metabolites (11-OH-THC and THCCOOH) are present in blood and hair, 9THC in saliva, and THCCOOH in urine. 9THC and related compounds are determined in autopsy material, although deaths by overdose of cannabis are exceptionally rare. Fatalities happen most often after intravenous injection of hashish oil. 9THC and its metabolites determination in different biological materials gives the basis for a wide interpretation of analytical results for clinical and forensic toxicology purposes.

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…

Current Perspectives on Biotechnological Cannabinoid Production in Plants.

PubMed

Schachtsiek, Julia; Warzecha, Heribert; Kayser, Oliver; Stehle, Felix

2018-03-01

The plant Cannabis sativa contains a number of psychoactive chemical compounds, the cannabinoids, which possess a significant pharmaceutical potential. Recently, the usage of Cannabis for medicinal purposes was legalized in many countries. Thus, the study on the influence of different cannabinoids in combination with other Cannabis -derived compounds with respect to the treatment of various diseases becomes increasingly important. Besides the production of distinct cannabinoids in a heterologous host, like tobacco or yeast, transgenic Cannabis plants would be a suitable alternative to modify and therefore optimize the cannabinoid profile. This perspective highlights the current efforts on Cannabis cell culture systems, in vitro propagation, and transformation of the plant and reveals the resulting opportunities concerning biotechnological production of cannabinoids. Furthermore, alternative platform organisms for the heterologous production of cannabinoids, like tobacco, are considered and evaluated. Georg Thieme Verlag KG Stuttgart · New York.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2018-04-15

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2017-10-26

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

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.

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.

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.

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

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.

Epidemiology of betel quid usage.

PubMed

Gupta, P C; Ray, C S

2004-07-01

Betel quid chewing is an ancient practice common in many countries of Asia and among migrated communities in Africa, Europe and North America. It enjoys complete social acceptance in many societies and is also popular among women. In its most basic form, betel quid consists of betel leaf (Piper betel), areca nut, the main psychoactive ingredient, and slaked lime (calcium hydroxide). Areca nut is said to be the fourth most commonly used psychoactive substance in the world, after caffeine, nicotine and alcohol. There are a great variety of ingredients and ways of preparing betel quid in different countries. In some, particularly in India, tobacco is added to the quid. In recent years, commercially-manufactured non-perishable forms of betel quid (pan masala or betel quid mixtures and gutka), not containing betel leaf, have been marketed. Within a short period of about 2 decades, this industry has risen in value to several hundred US million dollars. Use of areca nut in any form is not safe for oral health; the use of commercially manufactured forms seems even riskier.

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.

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.

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.

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

Rapid screening and determination of 11 new psychoactive substances by direct analysis in real time mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry.

PubMed

Nie, Honggang; Li, Xianjiang; Hua, Zhendong; Pan, Wei; Bai, Yanping; Fu, Xiaofang

2016-08-01

With the amounts and types of new psychoactive substances (NPSs) increasing rapidly in recent years, an excellent high-throughput method for the analysis of these compounds is urgently needed. In this article, a rapid screening method and a quantitative analysis method for 11 NPSs are described and compared, respectively. A simple direct analysis in real time mass spectrometry (DART-MS) method was developed for the analysis of 11 NPSs including three categories of these substances present on the global market such as four cathinones, one phenylethylamine, and six synthetic cannabinoids. In order to analyze these compounds quantitatively with better accuracy and sensitivity, another rapid analytical method with a low limit of detection (LOD) was also developed using liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (LC/QTOFMS). The 11 NPSs could be determined within 0.5 min by DART-MS. Furthermore, they could also be separated and determined within 5 min by the LC/QTOFMS method. The two methods both showed good linearity with correlation coefficients (r(2) ) higher than 0.99. The LODs for all these target NPSs by DART-MS and LC/QTOFMS ranged from 5 to 40 ng mL(-1) and 0.1 to 1 ng mL(-1) , respectively. Confiscated samples, named as "music vanilla" and "bath salt", and 11 spiked samples were firstly screened by DART-MS and then determined by LC/QTOFMS. The identification of NPSs in confiscated materials was successfully achieved, and the proposed analytical methodology could offer rapid screening and accurate analysis results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

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.

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.

Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

PubMed

Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

2015-03-01

We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Nephrotoxic effects of designer drugs: synthetic is not better!

PubMed

Luciano, Randy L; Perazella, Mark A

2014-06-01

Designer drugs are synthetic, psychoactive substances with similar structures and activity to existing scheduled drugs or controlled chemical compounds. The use of these drugs is not generally considered illegal and they cannot be detected using standard toxicology tests--essentially they are considered to be 'legal highs'. Over the past several years, increasing numbers of designer drugs have become available. These drugs are classified as amphetamine derivatives, phenylpiperazine derivatives, synthetic cathinones, synthetic cannabinoids, phencyclidine derivatives and synthetic opioids. Although euphoria is the desired effect, neuropsychiatric and cardiac manifestations are frequently observed in individuals using these drugs at high doses or using drugs that are contaminated with other substances. Some designer drugs are also associated with adverse renal effects, including acute kidney injury from pigment nephropathy, acute tubular necrosis, obstructive nephropathy and hyponatraemia. The misuse of these drugs should be recognized and clinicians made aware of the potential for acute nephrotoxicity as the health burden of these compounds increases.

Determination of Tryptamines and β-Carbolines in Ayahuasca Beverage Consumed During Brazilian Religious Ceremonies.

PubMed

Santos, Mônica Cardoso; Navickiene, Sandro; Gaujac, Alain

2017-05-01

Ayahuasca is a potent hallucinogenic beverage prepared from Banisteriopsis caapi in combination with other psychoactive plants. N,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantified in ayahuasca samples using a simple and low-cost method based on SPE and LC with UV diode-array detection. The experimental variables that affect the SPE method, such as type of solid phase and nature of solvent, were optimized. The method showed good linearity (r > 0.9902) and repeatability (RSD < 0.8%) for alkaloid compounds, with an LOD of 0.12 mg/L. The proposed method was used to analyze 20 samples from an ayahuasca cooking process from a religious group located in the municipality of Fortaleza, state of Ceará, Brazil. The results showed that concentrations of the target compounds ranged from 0.3 to 36.7 g/L for these samples.

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

From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

PubMed Central

Hung, Ming Wai; Zhang, Zai Jun; Li, Shang; Lei, Benson; Yuan, Shuai; Cui, Guo Zhen; Man Hoi, Pui; Chan, Kelvin; Lee, Simon Ming Yuen

2012-01-01

The zebrafish (Danio rerio) has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model for in vivo high content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafish in vivo but not in vitro, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed. PMID:22919414

Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

PubMed

Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

2014-03-01

Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

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

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

PubMed

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Dried haematic microsamples and LC-MS/MS for the analysis of natural and synthetic cannabinoids.

PubMed

Protti, Michele; Rudge, James; Sberna, Angelo Eliseo; Gerra, Gilberto; Mercolini, Laura

2017-02-15

Synthetic cannabinoids are new psychoactive substances (NPS) with similar effects when compared to natural ones found in Cannabis derivatives. They have rapidly integrated into the illicit market, often sold as alternatives under international control. The need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological, forensic and anti-doping analysis. Dried blood spots have been used within the bioanalytical framework in place of plasma or serum, in order to reduce invasiveness, lower sample size, simplify handling, storage and shipping of samples and to facilitate home-based and on-field applications. However, DBS implementation has been limited mainly by concerns related to haematocrit effect on method accuracy. Volumetric absorptive microsampling (VAMS™), a second generation dried miniaturized sampling technology, has been developed just in order to eliminate haematocrit effect, thus providing accurate sampling but still granting feasible sample processing. An original LC-MS/MS method was herein developed and validated for the analysis of THC and its 2 main metabolites, together with 10 representative synthetic cannabinoids in both DBS and VAMS dried microsamples. The ultimate goal of this work is to provide highly innovative DBS and VAMS analytical protocols, whose performances were extensively optimized and compared, in order to provide effective and alternative tools that can be applied for natural and synthetic cannabinoid determination, in place of classical analytical strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Synthetic cannabinoids 2015: An update for pediatricians in clinical practice

PubMed Central

Castellanos, Daniel; Gralnik, Leonard M

2016-01-01

Synthetic cannabinoids are a group of substances in the world of designer drugs that have become increasingly popular over the past few years. Synthetic cannabinoids are a chemically diverse group of compounds functionally similar to THC. Since first appearing on the world market a few years ago these compounds have evolved rapidly. Newer more potent analogues have been developed. Identifying youth who abuse these substances can be difficult. Newer forms of consumption have also evolved. These products are now manufactured in products that look like natural cannabis resin and in liquid cartridges used in electronic cigarettes. Synthetic cannabinoids appear to be associated with potentially dangerous health effects that are more severe than that of marijuana. Some synthetic cannabinoid compounds have been associated with serious physical consequences, such as, seizures, myocardial infarction and renal damage. In addition, psychoactive effects, such as aggression, confusion, anxiety and psychosis have also been reported. The diagnosis remains primarily clinical with toxicological confirmation difficult due to manufacturers constantly developing new analogues to avoid detection. Pediatricians are urged to familiarize themselves with these drugs and the typical presentations of patients who use them. PMID:26862498

Direct analysis of psychoactive tryptamine and harmala alkaloids in the Amazonian botanical medicine ayahuasca by liquid chromatography-electrospray ionization-tandem mass spectrometry.

PubMed

McIlhenny, Ethan H; Pipkin, Kelly E; Standish, Leanna J; Wechkin, Hope A; Strassman, Rick; Barker, Steven A

2009-12-18

A direct injection/liquid chromatography-electrospray ionization-tandem mass spectrometry procedure has been developed for the simultaneous quantitation of 11 compounds potentially found in the increasingly popular Amazonian botanical medicine and religious sacrament ayahuasca. The method utilizes a deuterated internal standard for quantitation and affords rapid detection of the alkaloids by a simple dilution assay, requiring no extraction procedures. Further, the method demonstrates a high degree of specificity for the compounds in question, as well as low limits of detection and quantitation despite using samples for analysis that had been diluted up to 200:1. This approach also appears to eliminate potential matrix effects. Method bias for each compound, examined over a range of concentrations, was also determined as was inter- and intra-assay variation. Its application to the analysis of three different ayahuasca preparations is also described. This method should prove useful in the study of ayahuasca in clinical and ethnobotanical research as well as in forensic examinations of ayahuasca preparations.

[Professional drivers and psychoactive substances consumption: results from medical surveillance at the workplace in Piedmont region].

PubMed

Rosso, G L; Feola, M; Rubinetto, Maria Paola; Petti, N; Rubinetto, L

2011-01-01

The use of psychoactive substances has been shown to be a risk factor for accidents in professional drivers. According to an approved Italian law, in order to detect dependency at the workplace the occupational health physician is called to assess the use of illicit drugs among professional drivers. The main purpose of this study was to investigate the use of psychoactive substances among professional drivers. From July to December 2008, rapid urine screening test was carried out on 198 professional drivers. All positive results from the screening stage were verified by specialized laboratories. We found 4 workers with a positive rapid urine screening test (7.1%), one of which was positive only for benzodiazepines and another positive test was not confirmed by specialized laboratory. By only considering illegal substances detected, 6.1% of the drivers tested positive. In this study, the high number of consumers among professional drivers ranged from 31 to 35 years old. Cannabis (THC) was the most frequently detected substance (seen in 10 over 12 cases,), after that was methadone (2/12 cases) and cocaine (1/12 case). We only had one case where more than one substance was found in the same subject (THC and cocaine). Five (41.7%) were former drug-addicts and public Pathological Addiction Services (Ser.T.) had previously followed them. Our results highlight the problem of drug consumption among professional drivers in Piedmont region. Health education and medical surveillance in workplace drug-testing may improve worker and third parties safety.

Screening method for rapid classification of psychoactive substances in illicit tablets using mid infrared spectroscopy and PLS-DA.

PubMed

Pereira, Leandro S A; Lisboa, Fernanda L C; Coelho Neto, José; Valladão, Frederico N; Sena, Marcelo M

2018-05-09

Several new psychoactive substances (NPS) have reached the illegal drug market in recent years, and ecstasy-like tablets are one of the forms affected by this change. Cathinones and tryptamines have increasingly been found in ecstasy-like seized samples as well as other amphetamine type stimulants. A presumptive method for identifying different drugs in seized ecstasy tablets (n=92) using ATR-FTIR (attenuated total reflectance - Fourier transform infrared spectroscopy) and PLS-DA (partial least squares discriminant analysis) was developed. A hierarchical strategy of sequential modeling was performed with PLS-DA. The main model discriminated four classes: 5-MeO-MIPT, methylenedioxyamphetamines (MDMA and MDA), methamphetamine, and cathinones. Two submodels were built to identify drugs present in MDs and cathinones classes. Models were validated through the estimate of figures of merit. The average reliability rate (RLR) of the main model was 96.8% and accordance (ACC) was 100%. For the submodels, RLR and ACC were 100%. The reliability of the models was corroborated through their spectral interpretation. Thus, spectral assignments were performed by associating informative vectors of each specific modeled class to the respective drugs. The developed method is simple, fast, and can be applied to the forensic laboratory routine, leading to objective results reports useful for forensic scientists and law enforcement. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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.

The Relationship between Multiple Substance Use, Perceived Academic Achievements, and Selected Socio-Demographic Factors in a Polish Adolescent Sample.

PubMed

Mazur, Joanna; Tabak, Izabela; Dzielska, Anna; Wąż, Krzysztof; Oblacińska, Anna

2016-12-21

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.

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.

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.

[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.

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.

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.

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)

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.

Development of a new extraction technique and HPLC method for the analysis of non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp).

PubMed

Brighenti, Virginia; Pellati, Federica; Steinbach, Marleen; Maran, Davide; Benvenuti, Stefania

2017-09-05

The present work was aimed at the development and validation of a new, efficient and reliable technique for the analysis of the main non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp) inflorescences belonging to different varieties. This study was designed to identify samples with a high content of bioactive compounds, with a view to underscoring the importance of quality control in derived products as well. Different extraction methods, including dynamic maceration (DM), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical-fluid extraction (SFE) were applied and compared in order to obtain a high yield of the target analytes from hemp. Dynamic maceration for 45min with ethanol (EtOH) at room temperature proved to be the most suitable technique for the extraction of cannabinoids in hemp samples. The analysis of the target analytes in hemp extracts was carried out by developing a new reversed-phase high-performance liquid chromatography (HPLC) method coupled with diode array (UV/DAD) and electrospray ionization-mass spectrometry (ESI-MS) detection, by using an ion trap mass analyser. An Ascentis Express C 18 column (150mm×3.0mm I.D., 2.7μm) was selected for the HPLC analysis, with a mobile phase composed of 0.1% formic acid in both water and acetonitrile, under gradient elution. The application of the fused-core technology allowed us to obtain a significant improvement of the HPLC performance compared with that of conventional particulate stationary phases, with a shorter analysis time and a remarkable reduction of solvent usage. The analytical method optimized in this study was fully validated to show compliance with international requirements. Furthermore, it was applied to the characterization of nine hemp samples and six hemp-based pharmaceutical products. As such, it was demonstrated to be a very useful tool for the analysis of cannabinoids in both the plant material and its derivatives for pharmaceutical and nutraceutical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells

PubMed Central

Juknat, Ana; Pietr, Maciej; Kozela, Ewa; Rimmerman, Neta; Levy, Rivka; Coppola, Giovanni; Geschwind, Daniel; Vogel, Zvi

2012-01-01

BACKGROUND AND PURPOSE Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. We previously showed that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways. EXPERIMENTAL APPROACH To characterize the transcriptional effects of CBD and THC, we treated BV-2 microglial cells with these compounds and performed comparative microarray analysis using the Illumina MouseRef-8 BeadChip platform. Ingenuity Pathway Analysis was performed to identify functional subsets of genes and networks regulated by CBD and/or THC. KEY RESULTS Overall, CBD altered the expression of many more genes; from the 1298 transcripts found to be differentially regulated by the treatments, 680 gene probe sets were up-regulated by CBD and 58 by THC, and 524 gene products were down-regulated by CBD and only 36 by THC. CBD-specific gene expression profile showed changes associated with oxidative stress and glutathione depletion, normally occurring under nutrient limiting conditions or proteasome inhibition and involving the GCN2/eIF2α/p8/ATF4/CHOP-TRIB3 pathway. Furthermore, CBD-stimulated genes were shown to be controlled by nuclear factors known to be involved in the regulation of stress response and inflammation, mainly via the (EpRE/ARE)-Nrf2/ATF4 system and the Nrf2/Hmox1 axis. CONCLUSIONS AND IMPLICATIONS These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21542829

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.

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.

Caffeine and sulfadiazine interact differently with human serum albumin: A combined fluorescence and molecular docking study

NASA Astrophysics Data System (ADS)

Islam, Mullah Muhaiminul; Sonu, Vikash K.; Gashnga, Pynsakhiat Miki; Moyon, N. Shaemningwar; Mitra, Sivaprasad

2016-01-01

The interaction and binding behavior of the well-known drug sulfadiazine (SDZ) and psychoactive stimulant caffeine (CAF) with human serum albumin (HSA) was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of CAF is due to the formation of protein-drug complex in the ground state; whereas in case of SDZ, the experimental results were explained on the basis of sphere of action model. Although both these compounds bind preferentially in Sudlow's site 1 of the protein, the association constant is approximately two fold higher in case of SDZ (∼4.0 × 104 M-1) in comparison with CAF (∼9.3 × 102 M-1) and correlates well with physico-chemical properties like pKa and lipophilicity of the drugs. Temperature dependent fluorescence study reveals that both SDZ and CAF bind spontaneously with HSA. However, the binding of SDZ with the protein is mainly governed by the hydrophobic forces in contrast with that of CAF; where, the interaction is best explained in terms of electrostatic mechanism. Molecular docking calculation predicts the binding of these drugs in different location of sub-domain IIA in the protein structure.

Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops.

PubMed

Pijlman, F T A; Rigter, S M; Hoek, J; Goldschmidt, H M J; Niesink, R J M

2005-06-01

The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since 1999. This annual monitoring was issued by the Ministry of Health after reports of increased potency. The level of the main psychoactive compound, Delta9-tetrahydrocannabinol (THC), is measured in marijuana and hashish. A comparison is made between imported and Dutch preparations, and between seasons. Samples of cannabis preparations from randomly selected coffee shops were analyzed using gas chromatography (GC-FID) for THC, CBD and CBN. In 2004, the average THC level of Dutch home-grown marijuana (Nederwiet) (20.4% THC) was significantly higher than that of imported marijuana (7.0% THC). Hashish derived from Dutch marijuana (Nederhasj) contained 39.3% THC in 2004, compared with 18.2% THC in imported hashish. The average THC percentage of Dutch marijuana, Dutch hashish and imported hashish was significantly higher than in previous years. It nearly doubled over 5 years. During this period, the THC percentage in imported marijuana remained unchanged. A higher price had to be paid for cannabis with higher levels of THC. Whether the increase in THC levels causes increased health risks for users can only be concluded when more data are available on adjusted patterns of use, abuse liability, bioavailability and levels of THC in the brain.

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.

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

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.

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.

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.

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.

Psychoactive substances in seriously injured drivers in Denmark.

PubMed

Wiese Simonsen, K; Steentoft, A; Bernhoft, I M; Hels, T; Rasmussen, B S; Linnet, K

2013-01-10

This study assesses the presence of a number of psychoactive substances, including alcohol, based on blood samples from 840 seriously injured drivers admitted to five selected hospitals located in five different regions of Denmark. The study was a part of the EU 6th framework program DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines). Blood samples were screened for 30 illegal and legal psychoactive substances and metabolites as well as ethanol. Danish legal limits were used to evaluate the frequency of drivers violating the Danish legislation while limit of quantification (LOQ) was used for monitoring positive drivers. Tramadol is not included in the Danish legislation therefore the general cut off, as decided in the DRUID project was used. Overall, ethanol (18%) was the most frequently identified compound (alone or in combination with other drugs) exceeding the legal limit, which is 0.53g/l in Denmark. The percentage of seriously injured drivers testing positive for medicinal drugs at levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%) comprised the majority of this group. One or more illegal drugs (primarily amphetamines and cannabis) were found to be above the Danish legal limit in 4.9% of injured drivers. Young men (median age 31 years) were over-represented among injured drivers who violated Danish law for alcohol and drugs. Diazepam (4.4%), tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently detected at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphetamine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgonine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore, percentages are not mutually exclusive. Poly-drug use was observed in 112 (13%) seriously injured drivers. Tramadol was detected above DRUID cutoffs in 2.1% of seriously injured drivers. This is 3.5 times that observed in a Danish survey of randomly selected drivers. Moreover, illegal and medicinal drug levels above the Danish legal limit were present more than 10 times as frequently as in injured drivers, whereas ethanol was present more than 30 times as frequently than in randomly selected drivers. The results indicate that there is an increased risk in traffic when driving under the influence of psychoactive drugs, especially alcohol in young male drivers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market.

PubMed

de Boer, D; Bosman, I J; Hidvégi, E; Manzoni, C; Benkö, A A; dos Reys, L J; Maes, R A

2001-09-15

1-Aryl-piperazine compounds are, depending on their substituents, selective for certain serotonin receptors and together with their easy availability and their so-called legal status, this group of psychoactive compounds are potential designer drugs-of-abuse. Internet in that respect is an important source of information and distribution facilities. Because this development may have consequences for the interpretation of future clinical and forensic toxicological case studies, some analytical aspects of 1-benzyl-piperazine (BZP), 1-[4-methoxyphenyl]-piperazine (pMeOPP) and 1-[3-trifluoromethylphenyl]-piperazine (TFMPP) were studied. BZP was not detected by the AxSYM FPIA technology designed to determine amphetamine-like compounds, but had showed some cross reactivity with EMIT d.a.u.. The cross reactivities at 300 and 12,000ng/ml (RS)-amphetamine equivalents were 0.4 and 1.3%, respectively. Although BZP was not identified directly by the REMEDi HS Drug Profiling System, it can be detected by this HPLC/UV scanning system. Using GC/NPD without derivatisation, BZP, pMeOPP and TFMPP can be analysed for and applying GC/MS without or with acetylation or trifluoroacetylation, these compounds can be identified unambiguously. The usefulness of GC/NPD and GC/MS in this respect was demonstrated by the quantitative and qualitative analysis of the content of a capsule with the synthetic stimulant A2, which proved to contain 86.4mg of BZP.

[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.

Identification, occurrence and activity of quinazoline alkaloids in Peganum harmala.

PubMed

Herraiz, Tomás; Guillén, Hugo; Arán, Vicente J; Salgado, Antonio

2017-05-01

Peganum harmala L. is a medicinal plant from the Mediterranean region and Asia currently used for recreative psychoactive purposes (Ayahuasca analogue), and increasingly involved in toxic cases. Its psychopharmacological and toxicological properties are attributed to quinazoline and β-carboline alkaloids. In this work three major quinazoline alkaloids were isolated from P. harmala extracts and characterized as peganine (vasicine), deoxypeganine (deoxyvasicine) and a novel compound identified by HPLC-DAD-MS and NMR as peganine β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (peganine glycoside). Peganine appeared in flowers and leaves in high levels; high amounts of deoxypeganine and peganine were found in immature and green fruits whereas peganine and peganine glycoside accumulated in high amount in dry seeds reaching up to 1 and 3.9% (w/w), respectively. Roots and stems contained low amount of quinazolines. Seeds extracts containing both quinazoline and β-carboline alkaloids potently inhibited human monoamine oxidase (MAO)-A. However, quinazoline alkaloids did not contribute to MAO inhibition that was due to β-carbolines, suggesting that MAO-related psychoactive or toxic actions do not arise from quinazolines. Quinazoline alkaloids were poor radical scavengers in the ABTS assay whereas seed extracts had good activity. Quinazoline alkaloids are known to exert bronchodilator and abortifacient actions, and could contribute to such effects reported in P. harmala. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

Designer Drug (DD) abuse in Poland; a review of the psychoactive and toxic properties of substances found from seizures of illegal drug products and the legal consequences thereof. Part 1--cannabinoids and cathinones.

PubMed

Biliński, Przemysław; Hołownia, Piotr; Kapka-Skrzypczak, Lucyna; Wojtyła, Andrzej

2012-01-01

Faced with the rapidly growing increase of designer drug abuse, particularly amongst the younger generation, various legislative strategies are currently employed world-wide for tackling this problem - however with mixed results. The key issue is that the producers of DDs are able to either exploit existing legal substances intended for other uses, but which have been found to possess psychoactive properties, or to synthesise new psychoactive substances by introducing chemical modifications, often very minor ones, thereby avoiding the prohibited use of chemicals included on any banned lists. Some countries opt to ban new drugs as and when shown or considered to be harmful, while others introduce sweeping bans based on chemical structure. Nevertheless, an ever increasing diversity of new DDs are constantly appearing on domestic and Internet markets. Poland, together with the UK and Eire, has placed temporary bans on all DDs whenever they have been identified, thus enabling sufficient time for assessing their potential hazards to health. Part of this 'holding' strategy entails a thorough review of the scientific literature, including expert opinion when direct evidence is lacking, as well as information received from EU support organisations Europol and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). This paper, in two parts, therefore aims to provide an up-to-date summary review of available scientific evidence on the harm caused by the six main chemical groupings of DDs found in drug seizures of illegal products recently made in Poland. The first part is devoted to Cannabinoids and Cathinones derivatives. Ensuing legislation can therefore be rapidly formulated to make the bans permanent as appropriate.

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.

The future of type 1 cannabinoid receptor allosteric ligands.

PubMed

Alaverdashvili, Mariam; Laprairie, Robert B

2018-02-01

Allosteric modulation of the type 1 cannabinoid receptor (CB1R) holds great therapeutic potential. This is because allosteric modulators do not possess intrinsic efficacy, but instead augment (positive allosteric modulation) or diminish (negative allosteric modulation) the receptor's response to endogenous ligand. Consequently, CB1R allosteric modulators have an effect ceiling which allows for the tempering of CB1R signaling without the desensitization, tolerance, dependence, and psychoactivity associated with orthosteric compounds. Pain, movement disorders, epilepsy, obesity are all potential therapeutic targets for CB1R allosteric modulation. Several challenges exist for the development of CB1R allosteric modulators, such as receptor subtype specificity, translation to in vivo systems, and mixed allosteric/agonist/inverse agonist activity. Despite these challenges, elucidation of crystal structures of CB1R and compound design based on structure-activity relationships will advance the field. In this review, we will cover recent progress for CB1R allosteric modulators and discuss the future promise of this research.

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.

Human urinary metabolic patterns of the designer benzodiazepines flubromazolam and pyrazolam studied by liquid chromatography-high resolution mass spectrometry.

PubMed

Pettersson Bergstrand, Madeleine; Meyer, Markus R; Beck, Olof; Helander, Anders

2018-03-01

Over the past ~8 years, hundreds of unregulated new psychoactive substances (NPS) of various chemical categories have been introduced as recreational drugs through mainly open online trade. This study was performed to further investigate the human metabolic pattern of the NPS, or designer benzodiazepines flubromazolam and pyrazolam, and to propose analytical targets for urine drug testing of these substances. The urine samples originated from patient samples confirmed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis to contain flubromazolam or pyrazolam. The LC-HRMS/MS system consisted of a YMC-UltraHT Hydrosphere C18 column (YMC, Dinslaken, Germany) coupled to a Thermo Scientific (Waltham, MA, USA) Q Exactive Orbitrap MS operating in positive electrospray mode. The samples were analyzed both with and without enzymatic hydrolysis using β-glucuronidase. Besides the parent compounds, the main urinary excretion products were parent glucuronides, mono-hydroxy metabolites, and mono-hydroxy glucuronides. In samples prepared without hydrolysis, the most common flubromazolam metabolites were 1 of the mono-hydroxy glucuronides and 1 of the parent glucuronides. For pyrazolam, a parent glucuronide was the most common metabolite. These 3 metabolites were detected in all samples and were considered the primary targets for urine drug testing and confirmation of intake. After enzymatic hydrolysis of the urine samples, a 2-19-fold increase in the concentration of flubromazolam was found, highlighting the value of hydrolysis for this analyte. With hydrolysis, the flubromazolam hydroxy metabolites should be used as target metabolites. Copyright © 2017 John Wiley & Sons, Ltd.

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.

A cloud on the horizon-a survey into the use of electronic vaping devices for recreational drug and new psychoactive substance (NPS) administration.

PubMed

Blundell, M; Dargan, P; Wood, D

2018-01-01

There is limited published scientific data on vaping recreational drugs other than cannabis. A recent review suggested that 15% of people vaping cannabis have also vaped a synthetic cannabinoid receptor agonist (SCRA) and identified over 300 Internet reports of e-liquid manufacture of recreational drugs and/or new psychoactive substances (NPS). To determine the prevalence of use of electronic vaping devices for recreational drug and NPS delivery in the UK. A voluntary online survey using a convenience sample of UK adult participants (aged 16 years old and over) identified by a market research company. Data was collected regarding demographics, smoking history, electronic vaping device history and recreational drug/NPS use and route of administration. There were 2501 respondents. The mean (±SD) age was 46.2 ± 16.8 years old. The commonest lifetime recreational drug used was Cannabis (818, 32.7%). The majority of respondents had smoked (1545, 61.8%) with 731 (29.2%) being current smokers. The most commonly used SCRA product was 'Spice Gold' (173, 6.9%) and SCRA compound was ADB-CHMICA (48, 1.9%). 861 (34.4%) had used an electronic vaping device; 340 (13.6%) having used them for recreational drug administration; 236 (9.4%) reporting current use. The commonest lifetime recreational drug to be vaped was cannabis (155, 65.7%), with electronic cigarettes (230, 48.2%) being the commonest reported route of SCRA compound administration. 9.4% of respondents currently use electronic vaping devices for recreational drug administration with 6.2% reporting lifetime cannabis vaping use. Further larger scale studies are required to help inform the appropriate treatment and primary prevention strategies. © 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

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

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…

Multi-residue determination of 10 selected new psychoactive substances in wastewater samples by liquid chromatography-tandem mass spectrometry.

PubMed

Borova, Viola L; Gago-Ferrero, Pablo; Pistos, Constantinos; Thomaidis, Nikolaos S

2015-11-01

New psychoactive substances (NPSs) have become increasingly popular in recent years. The analysis of these substances in influent wastewater (IWW) can be used to track their use in communities. In addition, an evaluation of the amount of NPSs released to the aquatic environment can be performed through the analysis of effluent wastewater (EWW). This study presents the development, validation and application of an analytical methodology, based on solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the determination of 10 NPSs in IWW and EWW. Synthetic cannabinoids, cathinones, piperazines and pyrrolidophenones are included among the target analytes. To the authors' knowledge, it is the first time that eight out of these substances (4'-methylpyrrolidinobutyrophenone (MPPP), a-pyrrolidinopentiophenone (a-PVP), 2-[(1S,3R)-3-hydroxycyclohexyl]-5-(2-methyl-2-octanyl) phenol (CP47,497), (1-naphthyl(1-pentyl-1H-indol-3-yl) methanone (JWH-018), (1-butyl-1H-indol-3-yl)(1-naphthyl) methanone (JWH-073), (4-ethyl-1-naphthyl)(1-pentyl-1H-indol-3-yl) methanone (JWH-210), (4-methyl-1-naphthyl) (1-pentyl-1H-indol-3-yl) methanone (JWH-122) and 2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl) ethanone (JWH-250)) are investigated in wastewater. The optimized conditions for the analysis of this set of compounds included a SPE clean-up step using a polymeric sorbent and the use of a pentafluorophenyl (PFP) chromatographic column. Despite the broad range of physicochemical properties of the analytes the method allowed acceptable absolute recoveries (40-109%) for all the studied compounds at different levels of concentration. Low method limits of detection (MLODs) were achieved, ranging between 0.3 and 10 ng/L except for BZP and CP47,497 (20 and 23 ng/L, respectively), allowing a reliable and accurate quantification of the analytes. The method was successfully applied to the analysis of IWW and EWW samples from five wastewater treatment plants (WWTPs) located in Santorini Island (a highly touristic resort in Greece). Four out of 10 compounds (a-PVP, CP47,497, JWH-122 and JWH-210) were detected at least in one sample, being the first evidence of their presence in wastewater. CP47,497 was the most ubiquitous and abundant compound, showing concentrations up to 634 ng/L in some cases. Copyright © 2015 Elsevier B.V. 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.

Substance-related psychopathology and aggressiveness in a nightlife holiday resort: Results from a pilot study in a psychiatric inpatient unit in Ibiza.

PubMed

Martinotti, Giovanni; Cinosi, Eduardo; Santacroce, Rita; Papanti, Duccio; Pasquini, Anna; Mancini, Valerio; Corbo, Mariangela; Fiori, Federica; Sarchione, Fabiola; Marchetti, Daniela; Verrocchio, Maria Cristina; Di Giannantonio, Massimo; Torrens, Marta; Schifano, Fabrizio; Morlan Coarasa, Maria Jose; Merino Del Villar, Cristina

2017-05-01

We aimed to describe a sample of subjects admitted to a psychiatric unit after the intake of psychoactive substances for recreational purposes. Between June and September 2015, 49 subjects were included. Sociodemographic characteristics and psychopathological aspects were investigated, and urine samples for further analysis were collected. Three subgroups (cannabinoids, stimulants, and depressors users) were identified, according to the structured interview regarding substance use and urinalysis. Level of aggressiveness was found to be significantly higher (p < .05) in the cannabinoids subgroup. Self-reported symptom severity was comparable among groups, but trends could be identified: SCL-90 results showed a prevalence of anxiety symptoms among depressors users, hostility or aggression in the tetrahydrocannabinol subgroup, and psychoticism in the stimulants subgroup. The use of psychoactive substances was be characterised by poly-use of both traditional and novel substances. The presence of aggressiveness emerged as a main feature associated with the use of cannabis and other cannabinoids. Binge drinking and sleep deprivation also represented a relevant component in almost all the evaluated subjects. Copyright © 2017 John Wiley & Sons, Ltd.

Informal Trade of Psychoactive Herbal Products in the City of Diadema, SP, Brazil: Quality and Potential Risks

PubMed Central

Soares Neto, Julino Assunção Rodrigues; Kato, Edna Myiake; Galduróz, José Carlos F.; Marques, Luis Carlos; Macrini, Thiago; Rodrigues, Eliana

2013-01-01

The present study aimed to assess the quality and risks involved in the consumption of psychoactive herbal products (PHs) that are available through informal commerce in the city of Diadema, SP, Brazil. Methods of ethnography were used to conduct the fieldwork during which four dealers were selected to record the collection, handling, packaging, types of PHs marketed, and their therapeutic purposes. In addition, lots of the PHs selected were purchased from the dealers and analyzed using microbiology and pharmacognosy techniques. 217 PHs were recorded and categorized into two main groups: stimulants (67%) and depressants (27%) of the central nervous system; sixteen of them were selected, and their 52 lots were acquired. The deficiencies observed in handling and packaging these lots by dealers were confirmed by microbiological analysis; 80.8% of them presented risk according to the indicators defined by the Brazilian Pharmacopoeia. The pharmacognostic analysis confirmed the authenticity of only 9 to 16 PHs analyzed. In addition, descriptions of contraindications, adverse reactions, and drug interactions were found in the literature for the PHs. The results of this study allow the observation of the priorities for the sanitary adequacy of the popular trade of herbs. PMID:23818934

"Someone Else's Problem": New Psychoactive Substances in the Online Hungarian Media.

PubMed

Kassai, Szilvia; Rácz, József; Nagy, Alexandra; Bíbók, Tamás; Galambvári, Éva; Kilián, Csillag; Gyarmathy, V Anna

2017-01-01

Media monitoring is an important method to inform public health and prevention services about emerging health issues, such as new psychoactive substances (NPS). This study assessed the portrayal of NPS in online Hungarian media in 2015 using qualitative content analysis. Hungarian online media considers the dealer to be the main cause of drug use, which is portrayed as a problem for youth, poor people, minorities, and rural populations. The point of view of the articles is externalized, and so is the solution offered by them. From the perspective of the police or using a biomedical approach, the articles suggest that drug use is an individual (someone else's) problem, and the perspectives of insiders (such as users or addiction treatment professionals) are absent. The media portrays low socioeconomic background and the hopelessness of disadvantaged rural and mostly minority populations as the roots of NPS use, and misses the pressing incapability of health care emergency and drug treatment services to cope with the problem. The dominant portrayal of police raids is rarely counterbalanced by voices of active or recovering drug users or professionals in addiction treatment and harm reduction, who could offer a systematic solution to the apparent rapid spread of NPS use.

Medical cannabis vs. synthetic cannabinoids: What does the future hold?

PubMed

Bolognini, D; Ross, R A

2015-06-01

The medical use of cannabis has an intricate therapeutic history that finds its roots in ancient China (∼2700 BC). The main psychoactive component of cannabis, Δ(9) -tetrahydrocannabinol (Δ(9) -THC), was discovered in 1964. This was a significant breakthrough, as it allowed the generation of synthetic analogs of Δ(9) -THC, the discovery of cannabinoid receptors, and the generation of synthetic small molecules. Despite this, today there is still a paucity of drugs that target the cannabinoid system. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Cannabinoids: is there a potential treatment role in epilepsy?

PubMed

Blair, Robert E; Deshpande, Laxmikant S; DeLorenzo, Robert J

2015-01-01

Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management. While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established. This commentary will touch on our understanding of the brain endocannabinoid system's regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures. At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.

Cannabinoids: is there a potential treatment role in epilepsy?

PubMed Central

Blair, Robert E; Deshpande, Laxmikant S; DeLorenzo, Robert J

2016-01-01

Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management. While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established. This commentary will touch on our understanding of the brain endocannabinoid system’s regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures. At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy. PMID:26234319

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…

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

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.

Forensic applications of supercritical fluid chromatography - mass spectrometry.

PubMed

Pauk, Volodymyr; Lemr, Karel

2018-06-01

Achievements of supercritical fluid chromatography with mass spectrometric detection made in the field of forensic science during the last decade are reviewed. The main topics include analysis of traditional drugs of abuse (e.g. cannabis, methamphetamine) as well as new psychoactive substances (synthetic cannabinoids, cathinones and phenethylamines), doping agents (anabolic steroids, stimulants, diuretics, analgesics etc.) and chemical warfare agents. Control of food authenticity, detection of adulteration and identification of toxic substances in food are also pointed out. Main aspects of an analytical workflow, such as sample preparation, separation and detection are discussed. A special attention is paid to the performance characteristics and validation parameters of supercritical fluid chromatography-mass spectrometric methods in comparison with other separation techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

[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.

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.

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.

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 synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products.

PubMed

Uchiyama, Nahoko; Shimokawa, Yoshihiko; Kikura-Hanajiri, Ruri; Demizu, Yosuke; Goda, Yukihiro; Hakamatsuka, Takashi

Six new psychoactive substances were identified together with two other substances (compounds 1 - 8 ) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)- N -(naphthalen-1-yl)-1 H -indole-3-carboxamide, 2 ], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 ( 1 ). Two 2 H -indazole isomers of synthetic cannabinoids, AB-CHMINACA 2 H -indazole analog ( 3 ) and NNEI 2 H -indazole analog ( 4 ), were newly identified with 1 H -indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N -(naphthalen-1-yl) carbamate ( 5 ) and isobutyl 1-pentyl-1 H -indazole-3-carboxylate ( 6 ) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1 H -indazole. A phenethylamine derivative, N -OH-EDMA [ N -hydroxy-3,4-ethylenedioxy- N -methylamphetamine, 7 ], and a cathinone derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8 ), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.

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

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…

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…

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.

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.

Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants

PubMed Central

Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

2016-01-01

New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, “dark net”) as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated with “Spice” use, will be described (De Luca et al., 2015a). Considering the growing evidence of a widespread use of NPS, this review will be useful to understand the new trends in the field of drug reward and drug addiction by revealing the rewarding properties of NPS, and will be helpful to gather reliable data regarding the abuse potential of these compounds. PMID:27147945

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

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…

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

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

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.

Street-Like Synthesis of Krokodil Results in the Formation of an Enlarged Cluster of Known and New Morphinans.

PubMed

Soares, José Xavier; Alves, Emanuele Amorim; Silva, André M N; de Figueiredo, Natália Guimarães; Neves, João F; Cravo, Sara Manuela; Rangel, Maria; Netto, Annibal Duarte Pereira; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge; Afonso, Carlos Manuel

2017-08-21

"Krokodil" is the street name for a homemade injectable drug that has been used as a cheap substitute for heroin. Codeine is the opioid starting material for krokodil synthesis, and desomorphine is claimed to be the main opioid of krokodil and the main component responsible for its addictive and psychoactive characteristics. However, due to its peculiar manufacture, using cheap raw materials, krokodil is composed of a large and complex mixture of different substances. In order to shed some light upon the chemical complexity of krokodil, its profiling was conducted by reverse phase high performance liquid chromatography coupled to a photodiode array detector (RP-HPLC-DAD) and by liquid chromatography coupled to high resolution tandem mass spectrometry (LC-ESI-IT-Orbitrap-MS). Besides desomorphine, codeine, and morphine, profiting from the high resolution mass spectrometry (HRMS) data, an endeavor to study the morphinans content in krokodil was set for the first time. Considering codeine as the only morphinan precursor and the possible chemical transformations that can occur during krokodil synthesis, the morphinan chemical space was designed, and 95 compounds were defined. By making use of the morphinan chemical space in krokodil, the exact masses featured by HRMS, and the morphinan mass fragmentations patterns, a targeted identification approach was designed and implemented.The proposed 95 morphinans were searched using the full scan chromatogram of krokodil, and findings were validated by mass fragmentation of the correspondent precursor ions (MS 2 spectra). Following this effort, a total of 54 morphinans were detected, highlighting the fact that these additional morphinans may contribute to the psychotropic effects of krokodil.

Pharmacological characterization of a fluorescent uptake assay for the noradrenaline transporter.

PubMed

Haunsø, Anders; Buchanan, Dawn

2007-04-01

The noradrenaline transporter (NET) is a Na(+)/Cl(-) dependent monoamine transporter that mediates rapid clearance of noradrenaline from the synaptic cleft, thereby terminating neuronal signaling. NET is an important target for drug development and is known to be modulated by many psychoactive compounds, including psychostimulants and antidepressants. Here, the authors describe the development and pharmacological characterization of a nonhomogeneous fluorescent NET uptake assay using the compound 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP(+)). Data presented show that the pharmacology of both the classic radiolabeled (3)H-noradrenaline- and ASP(+)-based uptake assays are comparable, with an excellent correlation between potency obtained for known modulators of NET (r = 0.95, p < 0.0001). Furthermore, the fluorescent uptake assay is highly reproducible and has sufficiently large Z' values to be amenable for high-throughput screening (HTS). The advantage of this assay is compatibility with both 96- and 384-well formats and lack of radioactivity usage. Thus, the authors conclude that the assay is an inexpensive, viable approach for the identification and pharmacological profiling of small-molecule modulators of the monoamine transporter NET and may be amenable for HTS.

[New drugs of abuse on the Web: the role of the Psychonaut Web Mapping Project].

PubMed

Schifano, Fabrizio; Ricciardi, Alessandra; Corazza, Ornella; Deluca, Paolo; Davey, Zoe; Rafanelli, Chiara

2010-01-01

In the rapid change of drug scenarios, as the powerful development in the drug market, particularly in the number and the kind of the compound available, Internet plays a dominant role to become one of the major "drug market". The European Commission funded the Psychonaut Web Mapping Project (carried out in the time-frame January 2008-December 2009), with the aim to start/implement an Early Warning System (through the data/information collected from the Web virtual market), to identify and categorise novel recreational drugs/psychoactive compounds (synthetical/herbal drugs), and new trends in drug use to provide information for immediate and prevention intervention. The Psychonaut is a multi-site research project involving 8 research centres (De Sleutel, Belgium; University of Hertfordshire School of Pharmacy, St George's University of London, England; A-klinikkasäätiö, Finlandia; Klinik für Psychiatrie und Psychotherapie, Germany; Assessorato Salute Regione Marche, Italy; Drug Abuse Unit, Spain; Centre of Competence Bergen Clinics Foundation, Norway) based in 7 European Countries (England, Italy, Belgium, Finland, Germany, Spain, Norway).

Use of illicit substances among schoolchildren in colombo district, Sri Lanka.

PubMed

Liyanage, Isurujith Kongala; Wickramasinghe, Kremlin; Ratnayake, Himali Erandathie; Palmer, Paula; Matthews, David R; Katulanda, Prasad

2013-01-01

This study aimed to understand the usage patterns and correlates of illicit drug use among schoolchildren in Colombo district, Sri Lanka. A cross-sectional study was carried out among grade 10 and 12 students using a self-administered questionnaire. From the 6000 students selected, 5353(89.22%) responded. Betel chewing with tobacco was seen in 28.48% males and 10.44% females. Substances such as Barbul, Madana Modaka, and cough syrups that are not established as illicit drugs were used as psychoactive substances. Ingredients of some of these compounds are not fully understood or regulated. Prevalence of cannabis use was 3.85% in males and 0.24% in females. Studying nonscience subjects for Advanced Level, doing sports, low academic performance, and peer smoking significantly increased the odds of using one or more substances (P < .05). Many types of illicit substances were used by schoolchildren. More strategies to prevent further aggravation of these behaviors are needed. Constituents of some compounds are not understood and need further evaluation. Recognized high-risk groups can be targets for preventive and cessation programs.

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.

Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry.

PubMed

Bade, Richard; White, Jason M; Gerber, Cobus

2018-01-01

The combination of qualitative and quantitative bimonthly analysis of pharmaceuticals and illicit drugs using liquid chromatography coupled to mass spectrometry is presented. A liquid chromatography-quadrupole time of flight instrument equipped with Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in influent wastewater from two wastewater treatment plants in South Australia over a 14-month period. A total of 100 compounds were confirmed and/or detected using this strategy, with 61 confirmed in all samples including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA)), and known drug adulterants (lidocaine and tetramisole). A subset of these compounds was also included in a quantitative method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer. The use of illicit stimulants (methamphetamine) showed a clear decrease, levels of opioid analgesics (morphine and methadone) remained relatively stable, while the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and Alpha PVP) varied with no visible trend. This work demonstrates the value that high-frequency sampling combined with quantitative and qualitative analysis can deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South Australia.

Purity of synthetic cannabinoids sold online for recreational use.

PubMed

Ginsburg, Brett C; McMahon, Lance R; Sanchez, Jesus J; Javors, Martin A

2012-01-01

The recreational use of synthetic cannabinoids has recently increased. This increase is due, in part, to the recent availability of inexpensive compound sold legally online in bulk. In particular, JWH-018 (1-pentyl-3-(1-naphthoyl)indole) and JWH-073 (1-butyl-3-(1-naphthoyl)indole) have been found in herbal blends marketed as alternatives to cannabis. Although these particular compounds have recently been emergency scheduled in the United States, online suppliers have shifted sales to other, similar compounds that are not currently scheduled. However, the purity of the drugs obtained from online suppliers is not known. Relative purity of JWH-018 and JWH-073 from three different online suppliers was determined using high-performance liquid chromatography with ultraviolet detection and validated standards obtained from a traditional research chemical supplier. Our results show that JWH-018 and JWH-073 obtained from online vendors was of comparable purity to validated standards, even though the physical properties varied in color, texture, and odor. It is concluded that adverse events following consumption of synthetic cannabinoid preparations is unlikely to be due to impurities or residue from the manufacturing process, but rather to effects of the active drug or interactions with other psychoactive chemicals from herbs blended into products marketed as cannabis alternatives.

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

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.

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.

Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

PubMed

Asensi-Bernardi, Lucía; Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Sagrado, Salvador; Medina-Hernández, María José

2014-01-01

The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE. Copyright © 2013 John Wiley & Sons, Ltd.

[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.

Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis.

PubMed

Dolan, Sean B; Shetty, Ritu A; Forster, Michael J; Gatch, Michael B

2018-06-01

Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit "party pills" or "ecstasy" formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.

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.

The drug situation in Europe: an overview of data available on illicit drugs and new psychoactive substances from European monitoring in 2015.

PubMed

Mounteney, Jane; Griffiths, Paul; Sedefov, Roumen; Noor, Andre; Vicente, Julián; Simon, Roland

2016-01-01

A central task for the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is to produce an annual report of the latest data available on drug demand and drug supply in Europe. This paper is intended to facilitate a better understanding of, and easier access to, the main quantitative European level data sets available in 2015. The European reporting system formally covers all 28 European Union (EU) Member States, Norway and Turkey and incorporates multiple indicators alongside an early warning system (EWS) on uncontrolled new psychoactive substances (NPS). While epidemiological information is based largely on registries, surveys and other routine data reported annually, the EWS collects case-based data on an ongoing basis. The 2015 reporting exercise is centred primarily on a set of standardized reporting tools. The most recent data provided by European countries are presented, including data on drug use, drug-related morbidity and mortality, treatment demand, drug markets and new psychoactive substances, with data tables provided and methodological information. A number of key results are highlighted for illustrative purposes. Drug prevalence estimates from national surveys since 2012 (last year prevalence of use among the 15-34 age band) range from 0.4% in Turkey to 22.1% in France for cannabis, from 0.2% in Greece and Romania to 4.2% in the United Kingdom for cocaine, from 0.1% in Italy and Turkey to 3% in the Czech Republic and the United Kingdom for ecstasy, and from 0.1% or less in Romania, Italy and Portugal to 2.5% in Estonia for amphetamine. Declining trends in new HIV detections among people who inject drugs are illustrated, in addition to presentation of a breakdown of NPS reported to the EU early warning system, which have risen exponentially from fewer than 20 a year between 2005 and 2008, to 101 reported in 2014. Structured information is now available on patterns and trends in drug consumption in Europe, which permits triangulation of data from different sources and consideration of methodological limitations. Opioid drugs continue to place a burden on the drug treatment system, although both new heroin entrants and injecting show declines. More than 450 new psychoactive substances are now monitored by the European early warning system with 31 new synthetic cathinones and 30 new synthetic cannabinoid receptor agonists notified in 2014. © 2015 Society for the Study of Addiction.

[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.

Synthetic cannabinoid “Black Mamba” infidelity in patients presenting for emergency stabilization in Colorado: a P SCAN Cohort

PubMed Central

Brandehoff, Nicklaus; Adams, Axel; McDaniel, Kyle; Banister, Samuel D.; Gerona, Roy; Monte, Andrew A.

2017-01-01

Background Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. “Black Mamba”, often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death. Objectives We aim to identify the chemical constituents and quantification of eight cases of reported “Black Mamba” use in order to further understand the clinical variability in patients presenting for emergency stabilization. Methods We report data from eight cases of reported “Black Mamba” use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds. Results In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations. Conclusions The wide range of clinical presentations from “Black Mamba” use may be explained by the wide variability of chemical constituents found by laboratory analysis. PMID:28862050

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…

Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching.

PubMed

Dresen, S; Ferreirós, N; Gnann, H; Zimmermann, R; Weinmann, W

2010-04-01

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).

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

Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry.

PubMed

Vikingsson, Svante; Gréen, Henrik; Brinkhagen, Linda; Mukhtar, Shahzabe; Josefsson, Martin

2016-09-01

Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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.

[The awareness of addictive effect of nicotine --a questionnaire survey of students and employees of CM UMK].

PubMed

Karolczak, Dominika; Wilk, Magdalena; Błaszczyk, Agata; Szylberg, Łukasz; Seget, Monika; Florek, Ewa; Marszałek, Andrzej

2012-01-01

Tobacco is one of the main factors responsible for the development of human tumors, cardiovascular diseases and non-malignant respiratory diseases. Tobacco products are harmful to health and they contain nicotine, which is highly addictive. Many studies in humans and in animal models have shown that nicotine is addictive psychoactive drug, which triggers a cascade of neurobiological events in the brain reward centers leading to the intensity of behavior what aims to enhanced use of tobacco. In Poland the number of smokers is estimated at about 9.5 million people. Among active smokers is a significant number of medical students. 480 people have joined the study (253 women and 227 men): 416 student of Collegium Medicum in Bydgoszcz of Nicolaus Copernicus University in Torun (CM UMK), 59 students of biomedical engineering at the University of Technology and Life Sciences in Bydgoszcz and 5 employees of CM UMK. 13% of all respondents admitted to smoking cigarettes. Respondents students and university staff mainly responded affirmatively to the question about psychoactive addiction by smoking-Performed questionnaire also revealed a high awareness about the use of nicotine during smoking cessation. Most people had their first contact with tobacco smoke in the early years of life, meeting with tobacco smoke in the home and in school. A much smaller percentage of the students met for the first time to tobacco smoke in the later stages of education: high school and college. Even fewer respondents had their first encounter with tobacco smoke in the workplace. In summary, we can conclude that students and workers CM UMK show considerable awareness of the dangers of smoking and the addictive properties of tobacco smoke.

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

Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching

PubMed Central

Concheiro, Marta; Castaneto, Marisol; Kronstrand, Robert; Huestis, Marilyn A.

2015-01-01

The emergence of novel psychoactive substances is an ongoing challenge for analytical toxicologists. Different analogs are continuously introduced in the market to circumvent legislation and to enhance their pharmacological activity. Although detection of drugs in blood indicates recent exposure and link intoxication to the causative agent, urine is still the most preferred testing matrix in clinical and forensic settings. We developed a method for the simultaneous quantification of 8 piperazines, 4 designer amphetamines and 28 synthetic cathinones and 4 metabolites, in urine by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Data were acquired in full scan and data dependent MS2 mode. Compounds were quantified by precursor ion exact mass, and confirmed by product ion spectra library matching, taking into account product ions’ exact mass and intensities. One-hundred μL urine was subjected to solid phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase separation was achieved with gradient mobile phase of 0.1% formic acid in water and in acetonitrile in 20 min. The assay was linear from 2.5 or 5 to 500μg/L. Imprecision (n=15) was <15.4%, and accuracy (n=15) 84.2-118.5%. Extraction efficiency was 51.2-111.2%, process efficiency 57.7-104.9% and matrix effect ranged from -41.9 to 238.5% (CV<23.3%, except MDBZP CV<34%). Authentic urine specimens (n=62) were analyzed with the method that provides a comprehensive confirmation for 40 new stimulant drugs with specificity and sensitivity. PMID:25931378

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.

Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry.

PubMed

Grapp, Marcel; Kaufmann, Christoph; Streit, Frank; Binder, Lutz

2018-06-01

Comprehensive screening procedures for psychoactive agents in body fluids are an essential task in clinical and forensic toxicology. With the continuous emergence and adaption of new psychoactive substances (NPS) keeping a screening method up to date is challenging. To meet these demands, hyphenated high-resolution mass spectrometry has gained interest as extensive and expandable screening approach. Here we present a comprehensive method for systematic toxicological analysis of serum by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) with data independent acquisition. The potential of this method was demonstrated by analysis of 247 authentic serum- and 12 post-mortem femoral blood samples. Thus 950 compounds, comprising 185 different drugs and metabolites could be identified. For the detected substances, including pharmaceutical substances, illicit drugs as well as NPS, serum concentrations were confirmed ranging from traces to toxic values indicating the capability for forensic toxicological requirements. Positive identification of drugs was achieved by accurate mass measurement (±5ppm for [M+H] + ; ±10ppm for [M-H] - ), retention time (±0.35min), isotopic pattern match (less than 10 m/z RMS [ppm]), isotope match intensity (less than 20% RMS) and the presence of at least two fragment ions. The LC-QTOF-MS procedure was shown to be superior to serum screening by GC-MS, since 240% (335 versus 141) more drugs were identified in serum samples compared to GC-MS. Copyright © 2018 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.

Betel: consumption and consequences.

PubMed

Norton, S A

1998-01-01

Betel is a compound of natural substances chewed for its psychostimulating effects. Betel is composed of the nut of the areca palm (Areca catechu), the leaf of the betel pepper (Piper betle), and lime (calcium hydroxide). Approximately 200 million persons chew betel regularly throughout the western Pacific basin and south Asia. Only three drugs (nicotine, ethanol, and caffeine) are consumed more widely than betel. When betel is chewed, it produces mild psychoactive and cholinergic effects. There is copious production of a blood-red saliva that can stain oral structures. After years of chewing, the teeth may become red-brown to nearly black. Betel use is associated with oral leukoplakia, submucous fibrosis, and squamous cell carcinoma. Use of betel is discouraged in Western countries because of its alleged carcinogenic and perceived dysesthetic properties; nevertheless, betel is widely available in the West.

Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.

PubMed

Lam, Philip W; Frost, David W

2014-09-22

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation. 2014 BMJ Publishing Group Ltd.

Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation

PubMed Central

Rihel, Jason; Prober, David A.; Arvanites, Anthony; Lam, Kelvin; Zimmerman, Steven; Jang, Sumin; Haggarty, Stephen J.; Kokel, David; Rubin, Lee L.; Peterson, Randall T.; Schier, Alexander F.

2010-01-01

A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multi-dimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go-related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors. PMID:20075256

The endocannabinoid system and the brain.

PubMed

Mechoulam, Raphael; Parker, Linda A

2013-01-01

The psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), was isolated in the mid-1960s, but the cannabinoid receptors, CB1 and CB2, and the major endogenous cannabinoids (anandamide and 2-arachidonoyl glycerol) were identified only 20 to 25 years later. The cannabinoid system affects both central nervous system (CNS) and peripheral processes. In this review, we have tried to summarize research--with an emphasis on recent publications--on the actions of the endocannabinoid system on anxiety, depression, neurogenesis, reward, cognition, learning, and memory. The effects are at times biphasic--lower doses causing effects opposite to those seen at high doses. Recently, numerous endocannabinoid-like compounds have been identified in the brain. Only a few have been investigated for their CNS activity, and future investigations on their action may throw light on a wide spectrum of brain functions.

Neuropsychiatrie of biologische psychiatrie; een toekomstvisie in historisch perspectief.

PubMed

Verhoeven, W M; Tuinier, S

1999-06-01

Neuropsychiatry or Biological Psychiatry There is an urgent need to reconsider the position of psychiatry within the neurosciences because of the exploding knowledge about the relationship between brain and behaviour and the delay in implementation of new findings due to the separation of neurology and psychiatry. Biological psychiatry and psychopharmacology originate from the discovery by chance of psycho-active compounds in the early fifties and have contributed to the scientification of psychiatry. The impact of biological psychiatry for the pathophysiology of psychiatric disorders, however, is limited as a result of its biased orientation on neurotransmitters and receptors. The neuropsychiatric paradigm integrates knowledge from several domains, such as functional neuroanatomy, genetics and endocrinology and opens new vistas for the involvement of neuronal circuits in the initiation and maintenance of behavioural disturbances. In addition, novel and more specific treatment modalities may emerge.

What is the mechanism whereby cannabis use increases risk of psychosis?

PubMed

Luzi, Sonija; Morrison, Paul D; Powell, John; di Forti, Marta; Murray, Robin M

2008-10-01

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

Effects of Betel chewing on the central and autonomic nervous systems.

PubMed

Chu, N S

2001-01-01

Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity. Copyright 2001 National Science Council, ROC and S. Karger AG, Basel.

Classification and determination of cerebral biovailability of psychotropic drugs by quantitative "pharmaco-EEG" and psychometric investigations (studies with AX-A411-BS).

PubMed

Saletu, B; Grünberger, J; Linzmayer, L

1977-10-01

Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed.

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.

Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone-Based Cannabinoid Receptor Type 2 Ligands.

PubMed

Ragusa, Giulio; Bencivenni, Serena; Morales, Paula; Callaway, Tyra; Hurst, Dow P; Asproni, Battistina; Merighi, Stefania; Loriga, Giovanni; Pinna, Gerard A; Reggio, Patricia H; Gessi, Stefania; Murineddu, Gabriele

2018-03-25

In recent years, cannabinoid type 2 receptors (CB 2 R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB 2 R are devoid of the psychoactive effects typically observed for CB 1 R ligands. Based on our recent studies on a class of pyridazinone 4-carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure-activity relationships for this promising scaffold with the aim to develop potent CB 2 R ligands. In binding assays, two of the new synthesized compounds [6-(3,4-dichlorophenyl)-2-(4-fluorobenzyl)-cis-N-(4-methylcyclohexyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (2) and 6-(4-chloro-3-methylphenyl)-cis-N-(4-methylcyclohexyl)-3-oxo-2-pentyl-2,3-dihydropyridazine-4-carboxamide (22)] showed high CB 2 R affinity, with K i values of 2.1 and 1.6 nm, respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB 2 R inverse agonists. Compound 22 displayed the highest CB 2 R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle-switch residue, W6.48. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

[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.

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

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

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.

Screening new psychoactive substances in urban wastewater using high resolution mass spectrometry.

PubMed

González-Mariño, Iria; Gracia-Lor, Emma; Bagnati, Renzo; Martins, Claudia P B; Zuccato, Ettore; Castiglioni, Sara

2016-06-01

Analysis of drug residues in urban wastewater could complement epidemiological studies in detecting the use of new psychoactive substances (NPS), a continuously changing group of drugs hard to monitor by classical methods. We initially selected 52 NPS potentially used in Italy based on seizure data and consumption alerts provided by the Antidrug Police Department and the National Early Warning System. Using a linear ion trap-Orbitrap high resolution mass spectrometer, we designed a suspect screening and a target method approach and compared them for the analysis of 24 h wastewater samples collected at the treatment plant influents of four Italian cities. This highlighted the main limitations of these two approaches, so we could propose requirements for future research. A library of MS/MS spectra of 16 synthetic cathinones and 19 synthetic cannabinoids, for which analytical standards were acquired, was built at different collision energies and is available on request. The stability of synthetic cannabinoids was studied in analytical standards and wastewater, identifying the best analytical conditions for future studies. To the best of our knowledge, these are the first stability data on NPS. Few suspects were identified in Italian wastewater samples, in accordance with recent epidemiological data reporting a very low prevalence of use of NPS in Italy. This study outlines an analytical approach for NPS identification and measurement in urban wastewater and for estimating their use in the population.

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.

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

Groundwater dating with the helium-tritium method to assess the long-term persistence of pharmaceuticals and their residues in groundwater

NASA Astrophysics Data System (ADS)

Massmann, G.; Burke, V.; Hass, U.; Dünnbier, U.

2012-04-01

The helium-tritium dating method is based on the analysis of tritium combined with its decay product, the lighter and rare 3He isotope. It was first suggested by Tolstikhin and Kamenskiy (1969) and has since been used in many groundwater studies. We applied the method to date groundwater recharged by bank filtration and former sewage irrigation onto sewage farms in Berlin, Germany, in order to assess the long-term persistence of several organic trace pollutants. In recent years, the occurrence of organic trace pollutants, such as pharmaceuticals and personal care products (PPCPs) as well as their metabolites, in the aquatic environment has been of increasing public and scientific interest (e.g. Schwarzenbach et al., 2006). In (urban) partly closed water cycles like Berlin, poorly biodegradable polar compounds may travel along the water path from wastewater via surface water to the raw water used for drinking water production (Reemtsma et al., 2006). In addition, raw or treated sewage irrigation onto sewage farms and/or agricultural land was common practice in Berlin until the 80s. Combined age dating and trace compound analysis revealed that several phenazone-type compounds (AMDOPH, AMPH, FAA and AAA) as well as a number of psychoactive compounds (meprobamate, pyrithyldione, primidone, and its metabolites phenobarbital and phenylethylmalonamide) are present in three decade old groundwater down gradient of a decommissioned sewage farm in Berlin, while a number of phenazone-type compounds (phenazone, propyphenazone, AMDOPH, AMPH) were present in decade-old bank filtrate. The results prove the long-term-persistence of the respective compounds under anoxic redox conditions, which are prevalent at the investigated sites. At the bank filtration sites, some of the compounds may regionally even be used as time markers for a certain infiltration period and reflect the surface water quality changes of the past few decades.

Identification and analytical characterization of four synthetic cathinone derivatives iso-4-BMC, β-TH-naphyrone, mexedrone, and 4-MDMC.

PubMed

Qian, Zhenhua; Jia, Wei; Li, Tao; Liu, Cuimei; Hua, Zhendong

2017-02-01

New psychoactive substances (NPS) have gained much popularity on the global market over the last number of years. The synthetic cathinone family is one of the most prominent groups and this paper reports on the analytical properties of four synthetic cathinone derivatives: (1) 1-(4-bromophenyl)-1-(methylamino)propan-2-one (iso-4-BMC or iso-brephedrone), (2) 2-(pyrrolidin-1-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pentan-1-one (β-TH-naphyrone), (3) 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone), and (4) 2-(dimethylamino)-1-(4-methylphenyl)propan-1-one (4-MDMC). These identifications were based on liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. To our knowledge, no chemical or pharmacological data about compounds 1-3 have appeared until now, making this the first report on these compounds. The Raman and GC-MS data of 4 have been reported, but this study added the LC-MS and NMR data for additional characterization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid Screening Method for New Psychoactive Substances of Forensic Interest: Electrochemistry and Analytical Determination of Phenethylamines Derivatives (NBOMe) via Cyclic and Differential Pulse Voltammetry.

PubMed

Andrade, Ana Flávia B; Mamo, Samuel Kasahun; Gonzalez-Rodriguez, Jose

2017-02-07

The NBOMe derivatives are phenethylamines derived from the 2C class of hallucinogens. Only a few human pharmacologic studies have been conducted on these drugs, and several cases of intoxication and deaths have been reported. Presently, NBOMe are not a part of the routine drugs-of-abuse screening procedure for many police forces, and there are no rapid immunoassay screening tests that can detect the presence of those compounds. In this Article, the voltammetric behavior of 25B NBOMe and 25I NBOMe were investigated and their electroanalytical characteristics determined for the first time. A novel, fast, and sensitive screening method for the identification of the two most common NBOMes (25B-NBOMe and 25I-NBOMe) in real samples is reported. The method uses the electrochemical oxidation of these molecules to produce an analytical signal that can be related to the NBOMe concentration with an average lower limit of quantitation of 0.01 mg/mL for both of them. The method is selective enough to identify the two compounds individually, even given the great similarity in their structure.

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.

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.

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.

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

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.

[Analysis of intoxication with novel psychoactive substance (NPS) in Pomeranian region, from January to July 2015].

PubMed

Kabata, Piotr; Schetz, Daria; Waldman, Wojciech; Wiergowsk, Marek; Sein Anand, Jacek

2015-01-01

During initial months of the year 2015 we observed the increase number of patients intoxicated with NPS in Poland. In our work we analysed the scale of this phenomenon in Pomeranian region. Study was carried out on period from 1 January 2015 to 31 July 2015. Analysis was based on records derived from Electronic Poison Information Database developed and used on a daily basis on Pomeranian Centre of Toxicology (PCT), data obtained from Centre for Monitoring of Adverse Effects of Medicaments and Chemical Substances based in PCT and on information gathered from patients treated in Pomeranian Centre of Toxicology for NPS intoxication. Our study has shown slow, continuous rise in the number of intoxications with NPS in analysed period. The most frequent cause of intoxication were synthetic compounds. 99 cases needed treatment in Clinical Toxicology Unit due to their severe state. The youngest exposed person was 13 y.o., while the oldest was 53 y.o. Mean age was 22.5 y.o. with median 20 years. Majority of intoxications were among males (80.54%). 61.53% of all patients came from Tricity agglomeration. Ethanol was the prevalent coingestant. The most commonly used substance was generic NPS (70.59% of cases), followed by unknowns psychoactive substance (16.29% of cases), herbal mixture (16.29% of cases) and dextrometorphan (5.88% of cases). The study did not find one drug name that would be prevalent over others, with the most frequent commercial name being "Mocarz", found in 4 cases. Most dangerous substances found in NPS were PMA, PMMA, 25C-NBOMe and 251-NBOMe. There were no deaths of patients treated in PCT because of acute intoxication with NPS.

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/.

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.

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 novel screening method for 64 new psychoactive substances and 5 amphetamines in blood by LC-MS/MS and application to real cases.

PubMed

Vaiano, Fabio; Busardò, Francesco P; Palumbo, Diego; Kyriakou, Chrystalla; Fioravanti, Alessia; Catalani, Valeria; Mari, Francesco; Bertol, Elisabetta

2016-09-10

Identification and quantification of new psychoactive substances (NPS), both in biological and non-biological samples, represent a hard challenge for forensic toxicologists. NPS are increasingly emerging on illegal drug market. Many cases of co-consumption of NPS and other substances have also been reported. Hence, the development of analytical methods aiming at the detection of a broad-spectrum of compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully validated screening method in blood for the simultaneous detection of 69 substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones, 5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine, methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine, methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a dynamic multiple reaction monitoring analysis through liquid chromatography - tandem mass spectrometry (LC-MS/MS) is described. This method is very fast, easy to perform and cheap as it only requires the deproteinization of 200μL of blood sample with acetonitrile. The chromatographic separation is achieved with a C18 column. The analysis is very sensitive, with limits of quantification ranging from 0.1 to 0.5ng/mL. The method is linear from 1 to 100ng/mL and the coefficient of determination (R(2)) was always above 0.9900. Precision and accuracy were acceptable at any quality control level and recovery efficiency range was 72-110%. Matrix effects did not negatively affect the analytical sensitivity. This method was successfully applied to three real cases, allowing identification and quantification of: mephedrone and methamphetamine (post-mortem); ketamine, MDMA and MDA (post-mortem); AB-FUBINACA (ante-mortem). Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a GC-APCI-QTOFMS library for new psychoactive substances and comparison to a commercial ESI library.

PubMed

Mesihää, Samuel; Ketola, Raimo A; Pelander, Anna; Rasanen, Ilpo; Ojanperä, Ilkka

2017-03-01

Gas chromatography coupled to atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-APCI-QTOFMS) was evaluated for the identification of new psychoactive substances (NPS). An in-house high mass resolution GC-APCI-QTOFMS test library was developed for 29 nitrogen-containing drugs belonging mostly to synthetic stimulants. The library was based on 12 intra-day measurements of each compound at three different collision energies, 10, 20 and 40 eV. The in-house library mass spectra were compared to mass spectra from a commercial library constructed by liquid chromatography-electrospray ionization (LC-ESI) QTOFMS. The reversed library search scores between the in-house GC-APCI library and the commercial LC-ESI library were compared once a week during a 5-week period by using data measured by GC-APCI-QTOFMS. The protonated molecule was found for all drugs in the full scan mode, and the drugs were successfully identified by both libraries in the targeted MS/MS mode. The GC-APCI library score averaged over all collision energies was as high as 94.4/100 with a high repeatability, while the LC-ESI library score was also high (89.7/100) with a repeatability only slightly worse. These results highlight the merits of GC-APCI-QTOFMS in the analysis of NPS even in situations where the reference standards are not immediately available, taking advantage of the accurate mass measurement of the protonated molecule and product ions, and comparison to existing soft-ionization mass spectral libraries. Graphical abstract Tandem mass spectra obtained from GC-APCI-QTOFMS are comparable to LC-ESI-QTOFMS library spectra.

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.

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.

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

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.

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.

FAPA mass spectrometry of designer drugs.

PubMed

Smoluch, Marek; Gierczyk, Blazej; Reszke, Edward; Babij, Michal; Gotszalk, Teodor; Schroeder, Grzegorz; Silberring, Jerzy

2016-01-01

Application of a flowing atmospheric-pressure afterglow ion source for mass spectrometry (FAPA-MS) for the analysis of designer drugs is described. In this paper, we present application of FAPA MS for identification of exemplary psychotropic drugs: JWH-122, 4BMC, Pentedrone, 3,4-DNNC and ETH-CAT. We have utilized two approaches for introducing samples into the plasma stream; first in the form of a methanolic aerosol from the nebulizer, and the second based on a release of vapors from the electrically heated crucible by thermal desorption. The analytes were ionized by FAPA and identified in the mass analyzer. The order of release of the compounds depends on their volatility. These methods offer fast and reliable structural information, without pre-separation, and can be an alternative to the Electron Impact, GC/MS, and ESI for fast analysis of designer-, and other psychoactive drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

A review of lysergic acid diethylamide (LSD) in the treatment of addictions: historical perspectives and future prospects.

PubMed

Liester, Mitchell B

2014-01-01

Lysergic acid diethylamide (LSD) is a semisynthetic compound with strong psychoactive properties. Chemically related to serotonin, LSD was initially hypothesized to produce a psychosislike state. Later, LSD was reported to have benefits in the treatment of addictions. However, widespread indiscriminate use and reports of adverse affects resulted in the classification of LSD as an illicit drug with no accepted medical use. This article reviews LSD's storied history from its discovery, to its use as a research tool, followed by its widespread association with the counterculture movement of the 1960s, and finally to its rebirth as a medicine with potential benefits in the treatment of addictions. LSD's pharmacology, phenomenology, effects at neurotransmitter receptors, and effects on patterns of gene expression are reviewed. Based upon a review of the literature, it is concluded that further research into LSD's potential as a treatment for addictions is warranted.

Analysis of ultrasonic vocalizations emitted by infant rodents.

PubMed

Branchi, Igor; Santucci, Daniela; Alleva, Enrico

2006-01-01

Altricial rodent pups emit ultrasonic vocalizations (USVs), which are whistle-like sounds with frequencies between 30 and 90 kHz. These signals play an important communicative role in mother-offspring interaction because they elicit in the dam a prompt response as concerning care-giving behaviors. To investigate neurobehavioral development, the analysis of the number of USVs presents several advantages: (1) USVs are one of the few responses produced by very young rodents that can be quantitatively analyzed and elicited by quantifiable stimuli; (2) USV emission follows a clear ontogenetic profile from birth to the second to third week of life, thus allowing longitudinal analysis during very early post-natal ontogeny. The reported role played by several receptor agonists and antagonists in modulating the USV rate makes this measure highly informative in investigating the effects of toxicants and, more generally, psychoactive compounds on the development of selected brain systems.

Fentanyl novel derivative-related deaths.

PubMed

Giorgetti, Arianna; Centola, Carmela; Giorgetti, Raffaele

2017-05-01

Fentanyl (FEN) is a potent, synthetic narcotic used as an anaesthetic and a pain reliever, but also illegally manufactured. For diversion purpose, it is being steadily modified to produce new analogous compounds and derivatives (FENS), categorised as novel psychoactive substances. While potential FEN abuse is already known, even in the absence of a clear lethal dosage, there is still a shortage of data on its derivatives. A literature review of FENS-related deaths was performed, to better understand potential damage and future perspectives of FEN congeners. Epidemiological data, pathological findings, administration routes, average concentrations and lethal doses, toxicological issues, trends in misuses, comparison among FENS, and possible explanation for FENS abuse are reviewed and discussed in depth. This study provides a medical-legal and toxicological assessment of this phenomenon in order to understand the role of illegal fentanyl and its congeners in deaths from FENS overdose. Copyright © 2017 John Wiley & Sons, Ltd.

From the street to the laboratory: analytical profiles of methoxetamine, 3-methoxyeticyclidine and 3-methoxyphencyclidine and their determination in three biological matrices.

PubMed

De Paoli, Giorgia; Brandt, Simon D; Wallach, Jason; Archer, Roland P; Pounder, Derrick J

2013-06-01

Three psychoactive arylcyclohexylamines, advertised as "research chemicals," were obtained from an online retailer and characterized by gas chromatography ion trap electron and chemical ionization mass spectrometry, nuclear magnetic resonance spectroscopy and diode array detection. The three phencyclidines were identified as 2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone (methoxetamine), N-ethyl-1-(3-methoxyphenyl)cyclohexanamine and 1-[1-(3-methoxyphenyl)cyclohexyl]piperidine. A qualitative/quantitative method of analysis was developed and validated using liquid chromatography (HPLC) electrospray tandem mass spectrometry and ultraviolet (UV) detection for the determination of these compounds in blood, urine and vitreous humor. HPLC-UV proved to be a robust, accurate and precise method for the qualitative and quantitative analysis of these substances in biological fluids (0.16-5.0 mg/L), whereas the mass spectrometer was useful as a confirmatory tool.

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen

PubMed Central

Sullivan, Kelly G.; Levin, Michael

2016-01-01

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, we report results from a loss- and gain-of-function survey, using pharmacologic modulators of several neurotransmitter pathways to examine possible roles in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic, and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations including craniofacial defects, hyperpigmentation, muscle mispatterning, and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. PMID:27060969

The syntheses of 1-(2-thienyl)-2-(methylamino) propane (methiopropamine) and its 3-thienyl isomer for use as reference standards.

PubMed

Angelov, D; O'Brien, J; Kavanagh, P

2013-03-01

1-(2-Thienyl)-2-(methylamino)propane (methiopropamine, MPA), the thiophene analogue of methamphetamine, has recently appeared on a number of websites offering 'legal highs' for sale and has also been reported as a new psychoactive substance by the European Monitoring Centre for Drugs and Drugs Addiction (EMCDDA) Early Warning System. The drug is currently not controlled in the European Union (EU) but it would be expected that forensic laboratories will encounter it during routine analysis. As no reference standard was available, we have established a three-step protocol for its synthesis. We have also synthesized its 3-thienyl isomer and have established that this is separable from methiopropamine by gas chromatography using one of our routine protocols. The synthetic methodology presented here could be readily extended to the syntheses of analogous compounds. Copyright © 2011 John Wiley & Sons, Ltd.

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

Volatile Solvents as Drugs of Abuse: Focus on the Cortico-Mesolimbic Circuitry

PubMed Central

Beckley, Jacob T; Woodward, John J

2013-01-01

Volatile solvents such as those found in fuels, paints, and thinners are found throughout the world and are used in a variety of industrial applications. However, these compounds are also often intentionally inhaled at high concentrations to produce intoxication. While solvent use has been recognized as a potential drug problem for many years, research on the sites and mechanisms of action of these compounds lags behind that of other drugs of abuse. In this review, we first discuss the epidemiology of voluntary solvent use throughout the world and then consider what is known about their basic pharmacology and how this may explain their use as drugs of abuse. We next present data from preclinical and clinical studies indicating that these substances induce common addiction sequelae such as dependence, withdrawal, and cognitive impairments. We describe how toluene, the most commonly studied psychoactive volatile solvent, alters synaptic transmission in key brain circuits such as the mesolimbic dopamine system and medial prefrontal cortex (mPFC) that are thought to underlie addiction pathology. Finally, we make the case that activity in mPFC circuits is a critical regulator of the mesolimbic dopamine system's ability to respond to volatile solvents like toluene. Overall, this review provides evidence that volatile solvents have high abuse liability because of their selective effects on critical nodes of the addiction neurocircuitry, and underscores the need for more research into how these compounds induce adaptations in neural circuits that underlie addiction pathology. PMID:23954847

Monitoring novel psychoactive substances allegedly offered online for sale in Persian and Arabic languages.

PubMed

Corazza, Ornella; Assi, Sulaf; Malekianragheb, Saeideh; Beni, Mitra Naderi; Bigdeli, Imanollah; Aslanpour, Zoe; Schifano, Fabrizio

2014-07-01

Numbers of novel psychoactive substances (NPS) have been rapidly increasing over the past few years, with unprecedented challenges on traditional drug control systems. The web has been involved in the promotion and knowledge dissemination of NPS, which are being presented online as safer/legal alternatives to illicit drugs. The physical, psychological and social harms associated with NPS have been studied so far mainly in Europe and other English speaking countries. The aim of this research is to provide knowledge on the provision of NPS information/purchase opportunities to Middle East customers, whilst monitoring the Internet in Arabic and Farsi. Web analysis/assessments were carried out in both Farsi and Arabic between 2011 and 2013. Sources were scrutinized with the help of different search engines, including Google Arabic and Google Persian, to carry out searches focusing on both NPS retailers' and social network websites. The research identified 45 NPS apparently offered for purchase online. Most of these products were of synthetic origin; a few herbal stimulants were identified as well. The pro drug websites were not here easily identified, being hidden behind other, unrelated, websites. Present results may constitute a public health challenge to be considered at both national and worldwide level. New legislative frameworks should also be encouraged in order to ensure a better response to the current threat posed by rapid emergence of these substances. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

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.

Cross-sectional study to evaluate the longitudinal development of child and adolescent psychiatric diagnoses of inpatients in Vorarlberg, Austria.

PubMed

Schwarz, Karoline; Fuchs, Martin; Veraar, Maria; Menz, Wolfgang; Kemmler, Georg; Simma, Burkhard

2016-02-01

Clinical experience has repeatedly shown evidence for continuity between mental disorders in children and adolescents and mental disorders in adulthood. Up to now, Austria has had no epidemiologic data on psychiatric diseases in children and adolescents and their development into adulthood. How often do children and adolescents with psychiatric diseases have psychiatric diseases in adulthood? Is there any association between psychiatric diagnoses in childhood/adolescence and adulthood? Electronic medical records provided us with data on 2210 children and adolescents who were admitted to any hospital in the State of Vorarlberg, Austria, between 1997 and 2012 because of psychiatric diseases. In this cross-sectional study, diagnoses were coded according to ICD-10 and ICD-9 criteria. The three main reasons for admission of children and adolescents were substance abuse, emotional disorders and conduct disorders. Of the admitted children and adolescents, 9.8 % were readmitted to a psychiatric institution in adulthood. The main reason for readmission in adulthood appears to be disorders due to psychoactive substances (42.1 %). Of young patients with psychoactive substance use, 9.7 % were rehospitalized in adulthood, 70.8 % of them showed a diagnosis in the same category (F1) on admission. Children and adolescents admitted for schizophrenia, schizotypal, and delusional disorders (F2) were significantly more likely to be readmitted in adulthood (40.9 %) compared to any other child psychiatric diagnosis. This study once again shows the continuity of psychiatric disorders from childhood and adolescence to adulthood. It also gives further information about the transmission of diagnoses when patients reached the age of 18 years and their outcome. Until now, there is hardly any information about the outcome of children and adolescents with psychiatric diagnoses in Austria. We want to bring up more knowledge on that issue. Research findings may improve prevention and clinical assessment of children and adolescents with mental health problems.

The detection of NBOMe designer drugs on blotter paper by high resolution time-of-flight mass spectrometry (TOFMS) with and without chromatography.

PubMed

Botch-Jones, Sabra; Foss, Jamie; Barajas, David; Kero, Frank; Young, Craig; Weisenseel, Jason

2016-10-01

New psychoactive substances (NPS) have been associated with fatalities and severe injuries in a number of cases in the United States and have led investigators to rethink traditional drug monitoring protocols. Of particular interest are the variable phenethylamine chemical structures known as 'NBOMes', which pose an emerging threat to public health with incidence steadily growing over the past decade. In this study, direct sample analysis (DSA)-time of flight mass spectrometry was employed to leverage rapid and sensitive ambient ionization mass spectrometry without chromatographic separation as verified with an authentic case sample. Samples for method development were prepared at Boston University School of Medicine's Biomedical Forensic Sciences program (Boston, MA) and analyzed at the State of Maine Health and Environmental Testing Laboratory's Forensic Chemistry Section (Augusta, ME). Preliminary method development work was performed at the University of Central Florida (Orlando, FL). DSA without any extraction step in addition to the evaluation of methanol, dichloromethane and hexane extractions were conducted. Methanol was found to not be a suitable extraction solvent for DSA analysis of these compounds. For the screening of NBOMe designer drug variables on blotter paper, DSA-TOFMS was successful at reducing analysis time to ∼15s per sample, for qualitative identification for the selected analytes of interest. The analysis of an authentic forensic case sample by DSA-TOFMS using the method development parameters demonstrates its utility in forensic laboratories. 25C-NBOMe was identified with an exact mass accuracy of 0.60ppm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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

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.

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.

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.

Gas chromatographic analysis of dimethyltryptamine and beta-carboline alkaloids in ayahuasca, an Amazonian psychoactive plant beverage.

PubMed

Pires, Ana Paula Salum; De Oliveira, Carolina Dizioli Rodrigues; Moura, Sidnei; Dörr, Felipe Augusto; Silva, Wagner Abreu E; Yonamine, Mauricio

2009-01-01

Ayahuasca is obtained by infusing the pounded stems of Banisteriopsis caapi in combination with the leaves of Psychotria viridis. P. viridis is rich in the psychedelic indole N,N-dimethyltryptamine, whereas B. caapi contains substantial amounts of beta-carboline alkaloids, mainly harmine, harmaline and tetrahydroharmine, which are monoamine-oxidase inhibitors. Because of differences in composition in ayahuasca preparations, a method to measure their main active constituents is needed. To develop a gas chromatographic method for the simultaneous determination of dimethyltryptamine and the main beta-carbolines found in ayahuasca preparations. The alkaloids were extracted by means of solid phase extraction (C(18)) and detected by gas chromatography with nitrogen/phosphorous detector. The lower limit of quantification (LLOQ) was 0.02 mg/mL for all analytes. The calibration curves were linear over a concentration range of 0.02-4.0 mg/mL (r(2 )> 0.99). The method was also precise (RSD < 10%). A simple gas chromatographic method to determine the main alkaloids found in ayahuasca was developed and validated. The method can be useful to estimate administered doses in animals and humans for further pharmacological and toxicological investigations of ayahuasca. Copyright (c) 2009 John Wiley & Sons, Ltd.

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.

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.

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

Liquid chromatography-tandem mass spectrometry determination of synthetic cathinones and phenethylamines in influent wastewater of eight European cities.

PubMed

Bade, Richard; Bijlsma, Lubertus; Sancho, Juan V; Baz-Lomba, Jose A; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Gracia-Lor, Emma; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander L N; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Rousis, Nikolaos I; Ryu, Yeonsuk; Thomas, Kevin V; de Voogt, Pim; Zuccato, Ettore; Hernández, Félix

2017-02-01

The popularity of new psychoactive substances (NPS) has grown in recent years, with certain NPS commonly and preferentially consumed even following the introduction of preventative legislation. With the objective to improve the knowledge on the use of NPS, a rapid and very sensitive method was developed for the determination of ten priority NPS (N-ethylcathinone, methylenedioxypyrovalerone (MDPV), methylone, butylone, methedrone, mephedrone, naphyrone, 25-C-NBOMe, 25-I-NBOMe and 25-B-NBOMe) in influent wastewater. Sample clean-up and pre-concentration was made by off-line solid phase extraction (SPE) with Oasis MCX cartridges. Isotopically labelled internal standards were used to correct for matrix effects and potential SPE losses. Following chromatographic separation on a C 18 column within 6 min, the compounds were measured by tandem mass spectrometry in positive ionization mode. The method was optimised and validated for all compounds. Limits of quantification were evaluated by spiking influent wastewater samples at 1 or 5 ng/L. An investigation into the stability of these compounds in influent wastewater was also performed, showing that, following acidification at pH 2, all compounds were relatively stable for up to 7 days. The method was then applied to influent wastewater samples from eight European countries, in which mephedrone, methylone and MDPV were detected. This work reveals that although NPS use is not as extensive as for classic illicit drugs, the application of a highly sensitive analytical procedure makes their detection in wastewater possible. The developed analytical methodology forms the basis of a subsequent model-based back-calculation of abuse rate in urban areas (i.e. wastewater-based epidemiology). Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeting of the Orphan Receptor GPR35 by Pamoic Acid: A Potent Activator of Extracellular Signal-Regulated Kinase and β-Arrestin2 with Antinociceptive ActivityS⃞

PubMed Central

Zhao, Pingwei; Sharir, Haleli; Kapur, Ankur; Cowan, Alan; Geller, Ellen B.; Adler, Martin W.; Seltzman, Herbert H.; Reggio, Patricia H.; Heynen-Genel, Susanne; Sauer, Michelle; Chung, Thomas D.Y.; Bai, Yushi; Chen, Wei; Caron, Marc G.; Barak, Larry S.

2010-01-01

Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that pamoic acid is a potent GPR35 agonist. Pamoic acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that pamoic acid induces a Gi/o-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent. PMID:20826425

Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: Behavioral, electrophysiological and neurochemical evidence.

PubMed

Barbieri, M; Ossato, A; Canazza, I; Trapella, C; Borelli, A C; Beggiato, S; Rimondo, C; Serpelloni, G; Ferraro, L; Marti, M

2016-10-01

It is well known that an impairment of learning and memory function is one of the major physiological effects caused by natural or synthetic cannabinoid consumption in rodents, nonhuman primates and in humans. JWH-018 and its halogenated derivatives (JWH-018-Cl and JWH-018-Br) are synthetic CB1/CB2 cannabinoid agonists, illegally marketed as "Spice" and "herbal blend" for their Cannabis-like psychoactive effects. In the present study the effects of acute exposure to JWH-018, JWH-018-Cl, JWH-018-Br (JWH-018-R compounds) and Δ(9)-THC (for comparison) on Novel Object Recognition test (NOR) has been investigated in mice. Moreover, to better characterize the effects of JWH-018-R compounds on memory function, in vitro electrophysiological and neurochemical studies in hippocampal preparations have been performed. JWH-018, JWH-018-Cl and JWH-018-Br dose-dependently impaired both short- and long-memory retention in mice (respectively 2 and 24 h after training session). Their effects resulted more potent respect to that evoked by Δ(9)-THC. Moreover, in vitro studies showed as JWH-018-R compounds negatively affected electrically evoked synaptic transmission, LTP and aminoacid (glutamate and GABA) release in hippocampal slices. Behavioral, electrophysiological and neurochemical effects were fully prevented by CB1 receptor antagonist AM251 pretreatment, suggesting a CB1 receptor involvement. These data support the hypothesis that synthetic JWH-018-R compounds, as Δ(9)-THC, impair cognitive function in mice by interfering with hippocampal synaptic transmission and memory mechanisms. This data outline the danger that the use and/or abuse of these synthetic cannabinoids may represent for the cognitive process in human consumer. Copyright © 2016 Elsevier Ltd. All rights reserved.

[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.

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.

Betacaryophyllene - A phytocannabinoid as potential therapeutic modality for human sepsis?

PubMed

Meza, Angel; Lehmann, Christian

2018-01-01

Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis. Copyright © 2017 Elsevier Ltd. 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.

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.

[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.

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.

Caffeine: cognitive and physical performance enhancer or psychoactive drug?

PubMed

Cappelletti, Simone; Piacentino, Daria; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

2015-01-01

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.

Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?

PubMed Central

Cappelletti, Simone; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

2015-01-01

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting metabolism alterations or diseases. PMID:26074744

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.

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.

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.

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.

'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.

Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats.

PubMed

Gatch, Michael B; Rutledge, Margaret A; Carbonaro, Theresa; Forster, Michael J

2009-07-01

There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects. The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (-)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (+/-)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in discriminative stimulus effects, each of the compounds was tested for substitution in all of the other training groups. LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM. DMT produces discriminative stimulus effects most similar to those of DOM, with some similarity to the discriminative stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.

Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens

PubMed Central

Lazarus, Michael; Shen, Hai-Ying; Cherasse, Yoan; Qu, Wei-Min; Huang, Zhi-Li; Bass, Caroline E.; Winsky-Sommerer, Raphaelle; Semba, Kazue; Fredholm, Bertil B.; Boison, Detlev; Hayaishi, Osamu; Urade, Yoshihiro; Chen, Jiang-Fan

2011-01-01

Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A2A receptors (A2ARs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A2ARs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A2ARs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A2ARs were focally removed from the NAc core or other A2AR-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain. PMID:21734299

Crystallization of Δ1-tetrahydrocannabinolic acid (THCA) synthase from Cannabis sativa

PubMed Central

Shoyama, Yoshinari; Takeuchi, Ayako; Taura, Futoshi; Tamada, Taro; Adachi, Motoyasu; Kuroki, Ryota; Shoyama, Yukihiro; Morimoto, Satoshi

2005-01-01

Δ1-Tetrahydrocannabinolic acid (THCA) synthase is a novel oxidoreductase that catalyzes the biosynthesis of the psychoactive compound THCA in Cannabis sativa (Mexican strain). In order to investigate the structure–function relationship of THCA synthase, this enzyme was overproduced in insect cells, purified and finally crystallized in 0.1 M HEPES buffer pH 7.5 containing 1.4 M sodium citrate. A single crystal suitable for X-ray diffraction measurement was obtained in 0.09 M HEPES buffer pH 7.5 containing 1.26 M sodium citrate. The crystal diffracted to 2.7 Å resolution at beamline BL41XU, SPring-8. The crystal belonged to the primitive cubic space group P432, with unit-cell parameters a = b = c = 178.2 Å. The calculated Matthews coefficient was approximately 4.1 or 2.0 Å3 Da−1 assuming the presence of one or two molecules of THCA synthase in the asymmetric unit, respectively. PMID:16511162

When color fails: illicit blue tablets containing anabolic androgen steroids.

PubMed

Favretto, Donata; Castagna, Franca; Maietti, Sergio; Boscolo-Berto, Rafael; Ferrara, Santo Davide

2013-09-01

The necessity of specific, confirmatory tests in the identification of seized illicit products was highlighted by the analysis of eighteen heart shaped, blue tablets confiscated by Police at a street control in the North East of Italy. The tablets responded as amphetamines to a preliminary color test (Marquis); a subsequent, confirmatory assay by gas chromatography-mass spectrometry revealed the presence of two anabolic androgen steroids (AAS), methandienone and methyltestosterone, in concentration of 1.7 and 1.5mg respectively per tablet; no trace of amphetamine-like or nitrogen containing compounds was found. The observed orange coloration was due to the reaction of concentrated sulphuric acid, contained in the Marquis reagent, with the Δ(4) C-3 keto group of steroids. The two AAS, banned under the world antidoping code, are not considered as psychoactive drugs of abuse in most countries, although their trafficking may entangle severe public health concerns. Copyright © 2013 Elsevier B.V. All rights reserved.

Military chemical warfare agent human subjects testing: part 2--long-term health effects among participants of U.S. military chemical warfare agent testing.

PubMed

Brown, Mark

2009-10-01

Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents.

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.

Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

PubMed

Izzo, Angelo A; Borrelli, Francesca; Capasso, Raffaele; Di Marzo, Vincenzo; Mechoulam, Raphael

2009-10-01

Delta(9)-tetrahydrocannabinol binds cannabinoid (CB(1) and CB(2)) receptors, which are activated by endogenous compounds (endocannabinoids) and are involved in a wide range of physiopathological processes (e.g. modulation of neurotransmitter release, regulation of pain perception, and of cardiovascular, gastrointestinal and liver functions). The well-known psychotropic effects of Delta(9)-tetrahydrocannabinol, which are mediated by activation of brain CB(1) receptors, have greatly limited its clinical use. However, the plant Cannabis contains many cannabinoids with weak or no psychoactivity that, therapeutically, might be more promising than Delta(9)-tetrahydrocannabinol. Here, we provide an overview of the recent pharmacological advances, novel mechanisms of action, and potential therapeutic applications of such non-psychotropic plant-derived cannabinoids. Special emphasis is given to cannabidiol, the possible applications of which have recently emerged in inflammation, diabetes, cancer, affective and neurodegenerative diseases, and to Delta(9)-tetrahydrocannabivarin, a novel CB(1) antagonist which exerts potentially useful actions in the treatment of epilepsy and obesity.

Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats.

PubMed

Moreira, Eduardo L G; Rial, Daniel; Duarte, Filipe S; de Carvalho, Cristiane Ribeiro; Horst, Heros; Pizzolatti, Moacir G; Prediger, Rui D S; Ribeiro-do-Valle, Rosa Maria

2010-08-01

The aim of the present study was to evaluate the possible neurobehavioural effects in rats of the proanthocyanidin-rich fraction (PRF) isolated from the bark of Croton celtidifolius (Euphorbiaceae). Adult Wistar rats were treated with the PRF (0.3-30 mg/kg) and evaluated in different behavioural paradigms classically used for the screening of drugs with psychoactive effects. Acute intraperitoneal (i.p.) administration of PRF decreased spontaneous locomotor activity (open field arena and activity cage), enhanced the duration of ethyl ether-induced hypnosis, increased the latency to the first convulsion induced by pentylenetetrazole (60 mg/kg, i.p.) and attenuated apomorphine-induced (0.5 mg/kg, i.p.) stereotyped behaviour. In lower doses, PRF (0.3 or 3 mg/kg, i.p.) increased the frequency of open arm entries in the elevated plus-maze test. The present findings suggest that the systemic administration of PRF induces a wide spectrum of behavioural alterations in rats, consistent with the putative existence of hypnosedative, anticonvulsant and anxiolytic compounds.

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.

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.

Return of the lysergamides. Part III: Analytical characterization of N6 -ethyl-6-norlysergic acid diethylamide (ETH-LAD) and 1-propionyl ETH-LAD (1P-ETH-LAD).

PubMed

Brandt, Simon D; Kavanagh, Pierce V; Westphal, Folker; Elliott, Simon P; Wallach, Jason; Stratford, Alexander; Nichols, David E; Halberstadt, Adam L

2017-10-01

The psychoactive properties of lysergic acid diethylamide (LSD) have fascinated scientists across disciplines and the exploration of other analogues and derivatives has been motivated by deepening the understanding of ligand-receptor interactions at the molecular level as well as by the search for new therapeutics. Several LSD congeners have appeared on the new psychoactive substances (NPS) market in the form of blotters or powders. Examples include 1-propionyl-LSD (1P-LSD), AL-LAD, and LSZ. The absence of analytical data for novel compounds is a frequent challenge encountered in clinical and toxicological investigations. Two newly emerging lysergamides, namely N 6 -ethyl-6-norlysergic acid diethylamide (ETH-LAD) and 1P-ETH-LAD, were characterized by gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), GC solid-state infrared analysis, high performance liquid chromatography diode array detection as well as nuclear magnetic resonance spectroscopy. Limited analytical data for ETH-LAD were previously available, whereas information about 1P-ETH-LAD has not previously been encountered in the scientific literature. This study extends the characterization of lysergamides distributed on the NPS market, which will help to make analytical data available to clinicians, toxicologists, and other stakeholders who are likely to encounter these substances. The analysis of a test incubation of 1P-ETH-LAD with human serum at 37°C by LC single quadrupole MS at various time points (0-6 h, once per hour and one measurement after 24 h) revealed the formation of ETH-LAD, suggesting that 1P-ETH-LAD might serve as a pro-drug. 1P-ETH-LAD was still detectable in serum after 24 h. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

PubMed

Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC.

Identification of cellular and molecular factors determining the response of cancer cells to six ergot alkaloids.

PubMed

Mrusek, Marco; Seo, Ean-Jeong; Greten, Henry Johannes; Simon, Michael; Efferth, Thomas

2015-02-01

Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six ergot alkaloids (agroclavine, ergosterol, ergocornin E, ergotamine, dihydroergocristine, and 1-propylagroclavine tartrate) for their cytotoxicity towards tumor cell lines of the National Cancer Institute, USA. 1-Propylagroclavine tartrate (1-PAT) revealed the strongest cytotoxicity. Out of 76 clinically established anticancer drugs, cross-resistance was found between the ergot alkaloids and 6/7 anti-hormonal drugs (=85.7 %) and 5/15 DNA-alkylating drugs (=33.3 %). The IC50 values for the six alkaloids were not correlated to well-known determinants of drug resistance, such as proliferative activity (as measured by cell doubling times, PCNA expression, and cell cycle distribution), the multidrug resistance-mediating P-glycoprotein/MDR1 and expression or mutations of oncogenes and tumor suppressor genes (EGFR, RAS, TP53). While resistance of control drugs (daunorubicin, cisplatin, erlotinib) correlated with these classical resistance mechanisms, ergot alkaloids did not. Furthermore, COMPARE and hierarchical cluster analyses were performed of mRNA microarray data to identify genes correlating with sensitivity or resistance to 1-PAT. Twenty-three genes were found with different biological functions (signal transducers, RNA metabolism, ribosome constituents, cell cycle and apoptosis regulators etc.). The expression of only 3/66 neuroreceptor genes correlated with the IC50 values for 1-PAT, suggesting that the psychoactive effects of ergot alkaloids may not play a major role for the cytotoxic activity against cancer cells. In conclusion, the cytotoxicity of ergot alkaloids is not involved in classical mechanisms of drug resistance opening the possibility to bypass resistance and to treat otherwise drug-resistant and refractory tumors. The modes of action are multifactorial, which is a typical feature of many natural compounds.

Systematic analytical characterization of new psychoactive substances: A case study.

PubMed

Lobo Vicente, Joana; Chassaigne, Hubert; Holland, Margaret V; Reniero, Fabiano; Kolář, Kamil; Tirendi, Salvatore; Vandecasteele, Ine; Vinckier, Inge; Guillou, Claude

2016-08-01

New psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as "legal highs". They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market. In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being "white pigments". For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier-Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools. The aim of this study was also to encourage the development of a science-based policy driven approach on NPS. These samples were fully characterized and identified as 5F-AMB and PX-3 using (1)H and (13)C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and structural information. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012-2013.

PubMed

Institóris, László; Árok, Zsófia; Seprenyi, Katalin; Varga, Tibor; Sára-Klausz, Gabriella; Keller, Éva; Tóth, Réka A; Sala, Leonardo; Kereszty, Éva; Róna, Kálmán

2015-03-01

Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC-MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County - neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs - generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances ("Schedule C"). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atropa belladonna intoxication: a case report.

PubMed

Berdai, Mohamed Adnane; Labib, Smael; Chetouani, Khadija; Harandou, Mustapha

2012-01-01

Atropa belladonna is a poisonous plant also called deadly nightshade. Its roots, leaves and fruits contain alkaloids: atropine, hyocyamine and scopolamine. The risk of poisoning in children is important because of possible confusion with other berries. Atropa belladonna acute intoxication is a severe condition, it's should be considered in the presence of anti-cholinergic toxidrome, the differential diagnosis include other plants or psychoactive drugs containing atropine. The treatment is mainly symptomatic including gastrointestinal decontamination with activated charcoal. In severe cases, physostigmine can be used as an antidote. We report the case of 11 year old girl with Atropa belladonna poisoning which was administrated in a therapeutic purpose as a remedy to jaundice. The child presented essentially a central anti-cholinergic syndrome. She was admitted in the intensive care unit, the progression was favorable with symptomatic treatment.

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

PubMed

de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

2015-11-03

The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

Neurocognitive Correlates in Driving Under the Influence of Cannabis.

PubMed

Busardò, Francesco P; Pellegrini, Manuela; Klein, Julia; di Luca, Natale M

2017-01-01

Delta (9)-tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis and is frequently identified in blood samples from apprehended drivers suspected for driving under the influence of drugs. Changing social norms towards cannabis and higher acceptability towards the drug emphasize the need for in-depth understanding of the acute neurocognitive and psychomotor effects caused by cannabis and how these effects are correlated to driving skills and performance. In this review, PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar databases were used to identify and select publications up to January 2017 dealing with acute and chronic neurocognitive effects induced by cannabis and ability to drive. Thirty-six publications were selected for this review. The studies conducted were experimental, using simulators or on-road studies and brain imaging (structural and functional) to better understand the acute and chronic effects on cognitive functions comprised in the short and long-term fitness to drive after cannabis consumption. In a case-crossover self-report study a significant odds ratio increase was found for driving- related injury after combined exposure to cannabis and alcohol compared to cannabis alone (OR of 10.9 and 5.8 respectively). Both, experimental and epidemiological studies have revealed that THC affects negatively both, psychomotor skills and cognitive functions. Studies of the acute effects of cannabis on driving have shown that drivers under the influence of this substance are impaired. Indeed, driving under the influence of cannabis doubles or triples the risk of a crash. Specifically, cannabis use impairs critical-tracking tasks, increases lane weaving, decreases reaction time, and divided attention. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification and physicochemical characterization of 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1-phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF) in seized materials and post-mortem biological samples.

PubMed

Rojkiewicz, Marcin; Majchrzak, Milena; Celiński, Rafał; Kuś, Piotr; Sajewicz, Mieczysław

2017-03-01

During the last decade, a substantial growth in new psychoactive substances (NPS) has been recorded. Within this group, a considerably fast-growing sub-group is represented by the opioids, which are based on modifications of the fentanyl structure. In this study, identification and analytical characterization of a new fentanyl derivative, 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1-phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF), is described. Apart from the seized powder, 4-FBF was also identified in the e-cigarette liquid secured in Case 1. The concentration of the compound in the liquid was 35 mg/mL. The main component of the liquid was glycerol, and nicotine was also present. This substance was detected in seized material that originated from the illegal drug market in Poland. To the best of the authors' knowledge, this report presents the first two analytically confirmed cases of fatal intoxication associated with 4-FBF. Case 1 was a 26-year-old male drug user who was found dead at home. Case 2 was a 25-year-old female, occasional user of NPS and drugs, who was also found dead at home. The concentrations of 4-FBF in blood were 91 and 112 ng/mL and in urine 200 and 414 ng/mL. The concentrations of 4-FBF in liver and kidney were 902 and 411 ng/g, and 136 and 197 ng/g, for Case 1 and Case 2, respectively. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

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.

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.

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.

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".

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

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.

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.

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.

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark.

PubMed

Simonsen, K Wiese; Steentoft, A; Hels, T; Bernhoft, I M; Rasmussen, B S; Linnet, K

2012-09-10

This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Oral fluid samples (n=3002) were collected randomly from drivers using a sampling scheme stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53g/l, which is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted mainly of young men (median age 26 years). Middle aged women (median age 44.5 years) often tested positive for benzodiazepines at concentrations exceeding the legal limits. Interestingly, 0.6% of drivers tested positive for tramadol, at concentrations above the DRUID cut off; although, tramadol is not included in the Danish list of narcotic drugs. It can be concluded that driving under the influence of drugs is as serious a road safety problem as drunk driving. Copyright © 2012. Published by Elsevier Ireland Ltd.

Physical activity to overcome the adversity of widowhood: Benefits beyond physical health.

PubMed

Li, Chu-Shiu; Lee, June Han; Chang, Ly-Yun; Liu, Chwen-Chi; Chan, Yan-Lan; Wen, Christopher; Chiu, Mu-Lin; Tsai, Min Kuang; Tsai, Shan Pou; Wai, Jackson Pui Man; Tsao, Chwen Keng; Wu, Xifeng; Wen, Chi Pang

2016-08-01

Widowhood has been increasingly encountered because of increasing longevity of women, often characterized by social stigmatization and poor physical and mental health. However, applied research to overcome its adversity has been quite limited. The goal of this study is to explore the role of physical activity in improving the health of widows.A cohort of 446,582 adults in Taiwan who successively participated in a comprehensive medical screening program starting in 1994, including 232,788 women, was followed up for mortality until 2008. Each individual provided detailed health history, and extensive lab tests results.The number of widows increased with time trend. Every other woman above age 65 was a widow (44%). Widows were less active, more obese, and smoked and drank more, had sleep problems, were more depressed with taking sedatives or psychoactive drugs, leading to more suicides. In the global development of health policies by World Health Organization (WHO), physical activity is one of the main factors to reverse poor health. The poor health of inactive widow was mitigated when becoming fully active in this study. Exercise not only reduced the observed 18% increase in all-cause mortality, but also gained 4 years and as much as 14% mortality advantage over the married but inactive. More importantly, becoming physically active energized their mental status, improved sleep quality and quantity, reduced depressions and the need for psychoactive drugs, and increased socialization circles.Widows, a rapidly growing and socially stigmatized group, suffered from social and financial inequality and tended to develop poorer health. Sustained physical activity could be one of the ways for them to overcome and reverse some of the physical and mental adversities of widowhood, and improve their quality and quantity of life.

Spatial clustering of mental disorders and associated characteristics of the neighbourhood context in Malmö, Sweden, in 2001

PubMed Central

Chaix, Basile; Leyland, Alastair H; Sabel, Clive E; Chauvin, Pierre; Råstam, Lennart; Kristersson, Håkan; Merlo, Juan

2006-01-01

Study objective Previous research provides preliminary evidence of spatial variations of mental disorders and associations between neighbourhood social context and mental health. This study expands past literature by (1) using spatial techniques, rather than multilevel models, to compare the spatial distributions of two groups of mental disorders (that is, disorders due to psychoactive substance use, and neurotic, stress related, and somatoform disorders); and (2) investigating the independent impact of contextual deprivation and neighbourhood social disorganisation on mental health, while assessing both the magnitude and the spatial scale of these effects. Design Using different spatial techniques, the study investigated mental disorders due to psychoactive substance use, and neurotic disorders. Participants All 89 285 persons aged 40–69 years residing in Malmö, Sweden, in 2001, geolocated to their place of residence. Main results The spatial scan statistic identified a large cluster of increased prevalence in a similar location for the two mental disorders in the northern part of Malmö. However, hierarchical geostatistical models showed that the two groups of disorders exhibited a different spatial distribution, in terms of both magnitude and spatial scale. Mental disorders due to substance consumption showed larger neighbourhood variations, and varied in space on a larger scale, than neurotic disorders. After adjustment for individual factors, the risk of substance related disorders increased with neighbourhood deprivation and neighbourhood social disorganisation. The risk of neurotic disorders only increased with contextual deprivation. Measuring contextual factors across continuous space, it was found that these associations operated on a local scale. Conclusions Taking space into account in the analyses permitted deeper insight into the contextual determinants of mental disorders. PMID:16614334

From ecstasy to MDMA: Recreational drug use, symbolic boundaries, and drug trends.

PubMed

Edland-Gryt, Marit; Sandberg, Sveinung; Pedersen, Willy

2017-12-01

Ecstasy pills with MDMA as the main ingredient were introduced in many European countries in the 1980s, and were often linked to the rave and club scenes. However, use gradually levelled off, in part as a response to increased concerns about possible mental health consequences and fatalities. Extensive use of MDMA now seems to be re-emerging in many countries. In this study, we investigated the cultural and social meaning associated with MDMA use in Oslo, Norway, with an emphasis on how users distinguish MDMA crystals and powder from "old ecstasy pills". Qualitative in-depth interviews (n=31, 61,3% males) were conducted with young adult party-goers and recreational MDMA/ecstasy users (20-34 years old, mean age 26.2 years). Research participants emphasised three important perceived differences between the MDMA crystals and ecstasy pills: (i) The effects of MDMA were described as better than ecstasy; (ii) MDMA was regarded as a safer drug; (iii) Users of MDMA crystals were described as more distinct from and less anchored in out-of-fashion rave culture than those using ecstasy. These differences were an important part of the symbolic boundary work MDMA users engaged in when justifying their drug use. MDMA has re-emerged as an important psychoactive substance in Oslo's club scene. One important reason for this re-emergence seems to be its perceived differentiation from ecstasy pills, even though the active ingredient in both drugs is MDMA. This perceived distinction between MDMA and ecstasy reveals the importance of social and symbolic meanings in relation to psychoactive substance use. Insights from this study can be important in terms of understanding how trends in drug use develop and how certain drugs gain or lose popularity. Copyright © 2017 Elsevier B.V. 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.

Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

PubMed

Abouchedid, Rachelle; Gilks, Thea; Dargan, Paul I; Archer, John R H; Wood, David M

2018-06-01

There has been increasing interest in the availability of non-prescription benzodiazepines and their sale as new psychoactive substances. We wanted to determine UK availability from Internet suppliers and motivations for use of three benzodiazepines (diclazepam, flubromazepam, and pyrazolam). In November 2014 and March 2016, using the European Monitoring Centre for Drugs and Drug Addiction Snapshot Methodology, Internet search engines ( google.co.uk , uk. yahoo.com and ask.com.uk ) were searched using the terms 'buy diclazepam', 'buy flubromazepam' and 'buy pyrazolam'. Threads from drug-user forums ( bluelight.org , drugs-forum.com , erowid.org , legalhighsforum.com ) were analysed using a general inductive approach. Data were converted into price per gram/pellet to allow cost comparisons and to determine motivations for use. There was an increase in websites selling these benzodiazepines between 2014 and 2016: diclazepam (49 in 2014 to 55 in 2016), pyrazolam (33 to 35), and flubromazepam (39 to 45). Thirty-eight (63.3%) sites were based in the UK/Europe. Drugs were sold as pellets (49 websites, 81.7%), powder (19, 31.7%), and blotters (1, 1.7%). Pill forms were not available, and one (1.7%) website sold diclazepam/flubromazepam in liquid form. The cost reduced with increasing purchase quantities. Main motivations for use included anxiolysis, management of benzodiazepine withdrawal, sedation/sleep aid, and management of stimulant withdrawal. These three benzodiazepines are widely available online, most commonly as pellets, and are (mis)used for a number of reasons. This study could be used to support triangulation of data from other sources to inform harm minimisation strategies.

Violence behavior and factors associated among students of Central-West Brazil.

PubMed

Castro, Marta de Lima; Cunha, Sergio Souza da; Souza, Delma P Oliveira de

2011-12-01

To estimate the prevalence of violence among adolescents and young adults and to identify associated factors. Cross-sectional study carried out in 2008 with systematic random sampling of 699 elementary and high school students enrolled in urban state schools of Barra do Garças, Central-Western Brazil. A self-administered questionnaire was applied in the classrooms without the presence of the teacher. The outcome "violent behavior" was defined as (1) use of firearm or sharp instrument, and/or (2) aggression against oneself and/or others, and/or (3) suicide attempt. The analyzed independent variables were age, gender, socioeconomic status, use of alcohol, use of psychoactive drugs, sexual activity, and relationship between parents. Univariate analysis was conducted, as well as multiple regression adjusted for effect of clustering. Violence prevalence was of 18.6%, varying with age: 10.1% in the group aged 10 and 11 years; 20.2% for those aged 12-19 years; and 4.5% in the group aged 20-21 years. The factors associated with violent behavior were use of alcohol (RP = 2.51, 95%CI 1.22;5.15), use of psychoactive drugs (RP = 2.10, 95%CI 1.61;2.75), male gender (RP = 1.63, 95%CI 1.13;2.35) and unsatisfactory relationship between parents (RP = 1.64, 95%CI 1.25;2.15). Results indicate high prevalence of violence among adolescents in the age group 12-19 years, mainly among users of alcohol and drugs, of the male sex, from families whose parents do not have satisfactory relationships. Although without statistical significance in the final regression model, school result discrepancy and socioeconomic level should be considered in educational actions for prevention of violence behavior among students.

Physical activity to overcome the adversity of widowhood

PubMed Central

Li, Chu-Shiu; Lee, June Han; Chang, Ly-yun; Liu, Chwen-Chi; Chan, Yan-Lan; Wen, Christopher; Chiu, Mu-Lin; Tsai, Min Kuang; Tsai, Shan Pou; Wai, Jackson Pui Man; Tsao, Chwen Keng; Wu, Xifeng; Wen, Chi Pang

2016-01-01

Abstract Widowhood has been increasingly encountered because of increasing longevity of women, often characterized by social stigmatization and poor physical and mental health. However, applied research to overcome its adversity has been quite limited. The goal of this study is to explore the role of physical activity in improving the health of widows. A cohort of 446,582 adults in Taiwan who successively participated in a comprehensive medical screening program starting in 1994, including 232,788 women, was followed up for mortality until 2008. Each individual provided detailed health history, and extensive lab tests results. The number of widows increased with time trend. Every other woman above age 65 was a widow (44%). Widows were less active, more obese, and smoked and drank more, had sleep problems, were more depressed with taking sedatives or psychoactive drugs, leading to more suicides. In the global development of health policies by World Health Organization (WHO), physical activity is one of the main factors to reverse poor health. The poor health of inactive widow was mitigated when becoming fully active in this study. Exercise not only reduced the observed 18% increase in all-cause mortality, but also gained 4 years and as much as 14% mortality advantage over the married but inactive. More importantly, becoming physically active energized their mental status, improved sleep quality and quantity, reduced depressions and the need for psychoactive drugs, and increased socialization circles. Widows, a rapidly growing and socially stigmatized group, suffered from social and financial inequality and tended to develop poorer health. Sustained physical activity could be one of the ways for them to overcome and reverse some of the physical and mental adversities of widowhood, and improve their quality and quantity of life. PMID:27512856

Which psychoactive substances are used by patients seen in the healthcare system in French overseas territories? Results of the OPPIDUM survey.

PubMed

Daveluy, Amélie; Frauger, Elisabeth; Peyrière, Hélène; Moracchini, Christophe; Haramburu, Françoise; Micallef, Joëlle

2017-02-01

Addiction to illicit substances or medicines is influenced by cultural, religious, ethnic factors as well as local availability. The purpose of this study was to evaluate the profile of drug users and characteristics of the psychoactive substances used in French overseas territories, using data from the OPPIDUM survey. OPPIDUM is an annual, nationwide, multicentric, cross-sectional study based on specialized care centres that included subjects presenting a drug addiction or under opiate maintenance treatment. The current study includes data from the 2012 and 2013 surveys and focuses on patients included by drug addiction centres located in French overseas departments and territories: French Pacific Ocean (French Polynesia, New Caledonia), French Americas (Guadeloupe, Saint Martin, French Guiana) and Reunion Island. Data from metropolitan France (2013 survey) were included as reference. Two hundred and forty-five patients were included. The sex ratio was 3.7 for the Pacific Ocean, 3.5 for the French Americas and 3.3 for Reunion Island. Cannabis was consumed in all the territories, from 50.8% in Reunion Island to 81.7% in Pacific Ocean. Cocaine was most frequently consumed in the French Americas (61%), mainly in the 'freebase' form (91%), whereas 6.5% of cocaine users in metropolitan France did so. Problematic use of medicines was most frequent in Reunion Island. Heroin seems rarely used in all overseas territories. This study highlights the complexity of substances used in French overseas territories, which often differ from that in mainland France. The relative difference between different areas provides valuable information for future investigations and possible interventions. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Comparison of the Discriminative Stimulus Effects of Dimethyltryptamine with Different Classes of Psychoactive Compounds in Rats

PubMed Central

Gatch, Michael B.; Rutledge, Margaret A.; Carbonaro, Theresa; Forster, Michael J.

2010-01-01

Rationale There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects. Objectives The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Methods Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (±)3,4-methylenedioxymethyl-amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in discriminative stimulus effects, each of the compounds was tested for substitution in all of the other training groups. Results LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM. Conclusions DMT produces discriminative stimulus effects most similar to those of DOM, with some similarity to the discriminative stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects. PMID:19288085

Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

PubMed

Keebaugh, Erin S; Park, Jin Hong; Su, Chenchen; Yamada, Ryuichi; Ja, William W

2017-11-01

Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine. We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains. Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake. Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell death.

PubMed

Wasik, Agata M; Gandy, Michael N; McIldowie, Matthew; Holder, Michelle J; Chamba, Anita; Challa, Anita; Lewis, Katie D; Young, Stephen P; Scheel-Toellner, Dagmar; Dyer, Martin J; Barnes, Nicholas M; Piggott, Matthew J; Gordon, John

2012-08-01

While 3,4-methylenedioxymethamphetamine (MDMA/'ecstasy') is cytostatic towards lymphoma cells in vitro, the concentrations required militate against its translation directly to a therapeutic in vivo. The possibility of 'redesigning the designer drug', separating desired anti-lymphoma activity from unwanted psychoactivity and neurotoxicity, was therefore mooted. From an initial analysis of MDMA analogues synthesized with a modified α-substituent, it was found that incorporating a phenyl group increased potency against sensitive, Bcl-2-deplete, Burkitt's lymphoma (BL) cells 10-fold relative to MDMA. From this lead, related analogs were synthesized with the 'best' compounds (containing 1- and 2-naphthyl and para-biphenyl substituents) some 100-fold more potent than MDMA versus the BL target. When assessed against derived lines from a diversity of B-cell tumors MDMA analogues were seen to impact the broad spectrum of malignancy. Expressing a BCL2 transgene in BL cells afforded only scant protection against the analogues and across the malignancies no significant correlation between constitutive Bcl-2 levels and sensitivity to compounds was observed. Bcl-2-deplete cells displayed hallmarks of apoptotic death in response to the analogues while BCL2 overexpressing equivalents died in a caspase-3-independent manner. Despite lymphoma cells expressing monoamine transporters, their pharmacological blockade failed to reverse the anti-lymphoma actions of the analogues studied. Neither did reactive oxygen species account for ensuing cell death. Enhanced cytotoxic performance did however track with predicted lipophilicity amongst the designed compounds. In conclusion, MDMA analogues have been discovered with enhanced cytotoxic efficacy against lymphoma subtypes amongst which high-level Bcl-2--often a barrier to drug performance for this indication--fails to protect.

An approach to shortening the timeframe between the emergence of new compounds on the drugs market and the availability of reference standards: The microscale syntheses of nitrazolam and clonazolam for use as reference materials, utilizing polymer-supported reagents.

PubMed

Dowling, Geraldine; Kavanagh, Pierce V; Eckhardt, Hans-Georg; Twamley, Brendan; Hessman, Gary; McLaughlin, Gavin; O'Brien, John; Brandt, Simon D

2018-03-15

Nitrazolam and clonazolam are 2 designer benzodiazepines available from Internet retailers. There is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material. Variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered form. The unavailability of reference standards can impact on the ability to identify these compounds. Therefore, the need arises for exploring in-house approaches to the preparation of new psychoactive substances (NPS) that can be carried out in a timely manner. The present study was triggered when samples of clonazolam were received in powdered and tablet form at a time when reference material for this drug was commercially unavailable. Therefore, microscale syntheses of clonazolam and its deschloro analog nitrazolam were developed utilizing polymer-supported reagents starting from 2-amino-2'-chloro-5-nitrobenzophenone (clonazolam) and 2-amino-5-nitrobenzophenone (nitrazolam). The final reaction step forming the 1,2,4-triazole ring moiety was performed within a gas chromatography-mass spectrometry (GC-MS) injector. A comparison with a preparative scale synthesis of both benzodiazepine derivatives showed that microscale synthesis might be an attractive option for a forensic laboratory in terms of time and cost savings when compared with traditional methods of synthesis and when qualitative identifications are needed to direct forensic casework. The reaction by-product profiles for both the micro and the preparative scale syntheses are also presented. Copyright © 2018 John Wiley & Sons, Ltd.

Identification and analytical characterization of nine synthetic cathinone derivatives N-ethylhexedrone, 4-Cl-pentedrone, 4-Cl-α-EAPP, propylone, N-ethylnorpentylone, 6-MeO-bk-MDMA, α-PiHP, 4-Cl-α-PHP, and 4-F-α-PHP.

PubMed

Liu, Cuimei; Jia, Wei; Li, Tao; Hua, Zhendong; Qian, Zhenhua

2017-08-01

Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances (NPS) phenomenon. In this study, the analytical characterization of nine synthetic cathinones is described: 2-(ethylamino)-1-phenylhexan-1-one (N-ethylhexedrone 1), 1-(4-chlorophenyl)-2-(methylamino)pentan-1-one (4-Cl-pentedrone 2), 1-(4-chlorophenyl)-2-(ethylamino)pentan-1-one (4-Cl-α-EAPP 3), 1-(3,4-methylenedioxyphenyl)-2-propylaminopropan-1-one (propylone 4), 1-(3,4-methylenedioxyphenyl)-2-ethylaminopentan-1-one (N-ethylnorpentylone 5), 1-(6-methoxy-3,4-methylenedioxyphenyl)-2-methylaminopropan-1-one (6-MeO-bk-MDMA 6), 4-methyl-1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PiHP 7), 1-(4-chlorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-Cl-α-PHP 8), and 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-F-α-PHP 9). The identification was based on ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. The mass-spectral fragmentations of these compounds following collision-induced dissociation (CID) and electron ionization (EI) were studied to assist forensic laboratories in identifying these compounds or other substances with similar structure in their case work. To our knowledge, no analytical data about the compounds 1-4, 7, and 8 have appeared until now, making this the first report on these compounds. The GC-MS data of 5, 6 and 9 has been reported, but this study added the LC-MS, Fourier Transform Infrared (FTIR) and NMR data for additional characterization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Psychostimulants and Movement Disorders

PubMed Central

Asser, Andres; Taba, Pille

2015-01-01

Psychostimulants are a diverse group of substances with their main psychomotor effects resembling those of amphetamine, methamphetamine, cocaine, or cathinone. Due to their potential as drugs of abuse, recreational use of most of these substances is illegal since 1971 Convention on Psychotropic Substances. In recent years, new psychoactive substances have emerged mainly as synthetic cathinones with new molecules frequently complementing the list. Psychostimulant related movement disorders are a known entity often seen in emergency rooms around the world. These admissions are becoming more frequent as are fatalities associated with drug abuse. Still the legal constraints of the novel synthetic molecules are bypassed. At the same time, chronic and permanent movement disorders are much less frequently encountered. These disorders frequently manifest as a combination of movement disorders. The more common symptoms include agitation, tremor, hyperkinetic and stereotypical movements, cognitive impairment, and also hyperthermia and cardiovascular dysfunction. The pathophysiological mechanisms behind the clinical manifestations have been researched for decades. The common denominator is the monoaminergic signaling. Dopamine has received the most attention but further research has demonstrated involvement of other pathways. Common mechanisms linking psychostimulant use and several movement disorders exist. PMID:25941511

Psychostimulants and movement disorders.

PubMed

Asser, Andres; Taba, Pille

2015-01-01

Psychostimulants are a diverse group of substances with their main psychomotor effects resembling those of amphetamine, methamphetamine, cocaine, or cathinone. Due to their potential as drugs of abuse, recreational use of most of these substances is illegal since 1971 Convention on Psychotropic Substances. In recent years, new psychoactive substances have emerged mainly as synthetic cathinones with new molecules frequently complementing the list. Psychostimulant related movement disorders are a known entity often seen in emergency rooms around the world. These admissions are becoming more frequent as are fatalities associated with drug abuse. Still the legal constraints of the novel synthetic molecules are bypassed. At the same time, chronic and permanent movement disorders are much less frequently encountered. These disorders frequently manifest as a combination of movement disorders. The more common symptoms include agitation, tremor, hyperkinetic and stereotypical movements, cognitive impairment, and also hyperthermia and cardiovascular dysfunction. The pathophysiological mechanisms behind the clinical manifestations have been researched for decades. The common denominator is the monoaminergic signaling. Dopamine has received the most attention but further research has demonstrated involvement of other pathways. Common mechanisms linking psychostimulant use and several movement disorders exist.

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.

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.

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.

The psychoactive ingredient of marijuana induces behavioural sensitization.

PubMed

Rubino, T; Viganò, D; Massi, P; Parolaro, D

2001-09-01

Here we describe, for the first time, the occurrence of behavioural sensitization after chronic exposure to Delta9-tetrahydrocannabinol. Rats were treated twice a day, for five days, with increasing doses (5, 10, 20, 40, 40 mg/kg i.p.) of Delta9-tetrahydrocannabinol or its vehicle and after 20 days of withdrawal, animals were challenged with 5 mg/kg (i.p.) of the drug and their behaviour was assessed. Contrary to the motor inhibition induced in control rats, challenge with Delta9-tetrahydrocannabinol in pre-exposed animals elicited a complex behavioural syndrome mainly characterized by oral stereotyped items. Due to the relevance of behavioural sensitization in drug-seeking behaviour that persists long after discontinuation of drug use, our findings suggest that cannabinoids could trigger neurobiological alteration not dissimilar from those observed with more harmful abused drugs.

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.

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.

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.

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.

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

[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.

P-glycoprotein interactions of novel psychoactive substances - stimulation of ATP consumption and transport across Caco-2 monolayers.

PubMed

Meyer, Markus R; Wagmann, Lea; Schneider-Daum, Nicole; Loretz, Brigitta; de Souza Carvalho, Cristiane; Lehr, Claus-Michael; Maurer, Hans H

2015-04-01

In contrast to drugs for therapeutic use, there are only few data available concerning interactions between P-glycoprotein (P-gp) and drugs of abuse (DOA). In this work, interactions between structurally diverse DOA and P-gp were investigated using different strategies. First, the effect on the P-gp ATPase activity was studied by monitoring of ATP consumption after addition to recombinant, human P-gp. Second, DOA showing an increased ATP consumption were further characterized regarding their transport across filter grown Caco-2- monolayers. Analyses were performed by luminescence and liquid chromatography-mass spectrometry, respectively. Among the nine DOA initially screened, benzedrone, diclofensine, glaucine, JWH-200, MDBC, WIN-55,212-2 showed an increase of ATP consumption in the ATPase stimulation assay. In Caco-2 transport studies, Glaucine, JWH-200, mitragynine, WIN-55,212-2 could moreover be identified as non-transported substrates, but inhibitors of P-gp activity. Thus, drug-drug or drug-food interactions should be very likely for these compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Analytical characterization of three cathinone derivatives, 4-MPD, 4F-PHP and bk-EPDP, purchased as bulk powder from online vendors.

PubMed

Apirakkan, Orapan; Frinculescu, Anca; Shine, Trevor; Parkin, Mark C; Cilibrizzi, Agostino; Frascione, Nunzianda; Abbate, Vincenzo

2018-02-01

Novel emerging drugs of abuse, also referred as new psychoactive substances, constitute an ever-changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One such class, synthetic cathinones, namely β-keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them. By using complementary analytical techniques (i.e. one- and two-dimensional NMR, FT-IR, GC-MS, HRMS and HPLC-UV), this study investigates the detection, identification and full characterization of 1-(4-methylphenyl)-2-(methylamino)pentanone (4-methylpentedrone, 4-MPD), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP), three emerging cathinone derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Stibathiolanes: Synthesis, solid state structure, and solution behavior

NASA Astrophysics Data System (ADS)

Fisher, Richard A.; Nielsen, Ralph B.; Davis, William M.; Buchwald, Stephen L.

1990-06-01

Interest in organometallic compounds of the main group metals has recently grown tremendously, due in part to the wide variety of applications of these compounds in the materials sciences. Despite this new activity, the synthetic strategies for main group organometallics have remained relatively undeveloped. The majority of syntheses of these compounds involve classical metathesis reactions between a main group halide and an organometallic compound such as an organolithium or Grignard reagent and are limited by a lack of selectivity and by the availability of suitable organometallic precursors. The latter limitation is severe for main group metallacycles because of the paucity of suitable 1, n(n=3,4,5)-dianionic reagents or their equivalents, which are most often used for the synthesis of this class of molecules.

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 ...

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.

[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.

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

Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.

PubMed

Shcherbinin, Sergey; Doyle, Orla; Zelaya, Fernando O; de Simoni, Sara; Mehta, Mitul A; Schwarz, Adam J

2015-11-01

Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug response in the presence of another, have not been widely investigated using a task-free ASL approach. We assessed the effects of three psychoactive compounds (ketamine, risperidone and lamotrigine), and their interaction, on resting brain perfusion in healthy human volunteers. A multivariate Gaussian process classification (GPC) and more conventional univariate analyses were applied. The four pre-infusion conditions for each subject comprised risperidone, lamotrigine and two placebo sessions. The two placebo conditions enabled us to evaluate the classification performance in a test-retest setting, in addition to its performance in distinguishing the active oral drugs from placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion scans allowed the effect of ketamine, and its interaction with risperidone and lamotrigine, on brain perfusion to be characterised. The pseudo-continuous ASL measurements of perfusion were sensitive to the effects of ketamine infusion and risperidone. The GPC captured consistent changes in perfusion across the group and contextualised the univariate changes with a larger pattern of regions contributing to accurate discrimination of ketamine from placebo. The findings argue against perfusion changes confounding in the previously described evoked BOLD response to ketamine and emphasise the blockade of the NMDA receptor over neuronal glutamate release in determining the perfusion changes induced by ketamine.

The syntheses, characterization and in vitro metabolism of nitracaine, methoxypiperamide and mephtetramine.

PubMed

Power, John D; Scott, Kenneth R; Gardner, Elizabeth A; Curran McAteer, Bronagh M; O'Brien, John E; Brehon, Margaret; Talbot, Brian; Kavanagh, Pierce V

2014-01-01

Three legal highs; nitracaine (3-(diethylamino)-2,2-dimethylpropyl 4-nitrobenzoate), methoxypiperamide (MEOP, (4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone) and mephtetramine (MTTA, 2-((methylamino)methyl)-3,4-dihydronaphthalen-1(2H)-one) appeared in 2013 as new psychoactive substances (NPS) on Internet websites selling 'research chemicals'. These compounds were synthesized and analyzed via our synthesize, analyze, and metabolize (SAM) protocol. Nitracaine was synthesized by the transesterification of methyl 4-nitrobenzoate with 3-(diethylamino)-2,2-dimethylpropan-1-ol. Methoxypiperamide was synthesized by the reaction of 4-methoxybenzoyl chloride with 1-methylpiperazine, and mephtetramine through the Mannich reaction of 1-tetralone with paraformaldehyde and methylamine hydrochloride. Each compound was characterized by nuclear magnetic resonance (NMR), gas chromatography with electron impact mass spectrometry (GC-EIMS), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and high resolution electrospray ionization mass spectrometry (HR-ESI-MS). A sample of nitracaine was also test-purchased from an Internet vendor and its structure confirmed by GC-EIMS and LC-ESI-MS. Finally, the in vitro metabolism of the nitracaine, mephtetramine, and methoxypiperamide was investigated, using a human microsomal liver extract, in order to tentatively identify potential metabolites that may be encountered in the analysis of biological samples in clinical or toxicology labs. The use of our SAM protocol highlights the ability of academic research labs to quickly respond to and disseminate information about emerging NPS. Copyright © 2014 John Wiley & Sons, Ltd.

Spicing thing up: Synthetic cannabinoids

PubMed Central

Spaderna, Max; Addy, Peter H; D’Souza, Deepak Cyril

2013-01-01

Rationale Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. Objectives The availability, acute subjective effects—including self-reports posted on Erowid—laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Results Spice is sold under the guise of potpourri or incense. Unlike THC, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid-receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned. Conclusions There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug-detection tests for synthetic cannabinoids need to become clinically available. PMID:23836028

Therapeutic potential of cannabinoids in schizophrenia.

PubMed

Kucerova, Jana; Tabiova, Katarina; Drago, Filippo; Micale, Vincenzo

2014-04-01

Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia. The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana's psychoactive principle Δ(9)-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation. It has been suggested to be a pro-homeostatic and pleiotropic signalling system activated in a time- and tissue-specific manner during pathophysiological conditions. In the brain, activation of this system impacts the release of numerous neurotransmitters in various systems and cytokines from glial cells. Hence, the endocannabinoid system is strongly involved in neuropsychiatric disorders, such as schizophrenia. Therefore, adolescence use of Cannabis may alter the endocannabinoid signalling and pose a potential environmental risk to develop psychosis. Consistently, preclinical and clinical studies have found a dysregulation in the endocannabinoid system such as changed expression of CB1 and CB2 receptors or altered levels of AEA and 2-AG . Thus, due to the partial efficacy of actual antipsychotics, compounds which modulate this system may provide a novel therapeutic target for the treatment of schizophrenia. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology. Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.

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.

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.

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 ...

[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.

[The relationship between the family structure and characteristics of the stress reaction in adolescent addicts].

PubMed

Ovchinnikov, A A; Sultanova, A N; Sycheva, T Yu; Mamedov, T N

2018-01-01

To study the relationship between the family structure and characteristics of the response to stress in adolescent addicts. The study included 65 patients who used psychoactive substances and 42 healthy controls. A set of psychological methods was used. In the group of adolescent addicts, a low result was revealed on the scale 'family cohesion'. A high level of development of such mechanisms of psychological defense as denial, suppression, repression, compensation, substitution, intellectualization and reactive education was diagnosed in both groups. Significant differences were revealed only in repression. Such stress coping strategies as self-control, escape-avoidance and problem-solving were more often used in the main group while confrontational coping, distancing, seeking social support, accepting responsibility and positive reassessment were used in the control group. Lower indices of resilience in adolescent addicts compared to the control group.

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

PubMed

Volkow, N D; Gillespie, H; Mullani, N; Tancredi, L; Grant, C; Valentine, A; Hollister, L

1996-05-31

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

[IMSS in numbers. Consumption of alcohol and psyhoactive substances].

PubMed

2005-01-01

One of the main public health problems in the world are alcohol and drug abuse. Health impact of addictions is clearly evidenced by the increasing numbers of suicides, depression, domestic violence, accidents and injuries. The mental and behavioral problems derived by the abuse of alcohol and psychoactive drugs are under reported. From 1991 to 2003 around 13,000 cases for problems due to alcohol abuse were reported annually in Family Medicine services, nearly 4000 cases in specialized services and an average of 20,000 cases were attended in the emergency areas of the social security system in Mexico (IMSS). The data indicates that this health problems are becoming evident in young populations under 25 years old and the trend is increasing. Professional resources that are specialized in the treatment of such behavioral problems are not sufficient and the institution faces an upcoming health threat that demands prevention programs and a more integrated health care programs.

Behavior and neuropsychiatric manifestations in Angelman syndrome

PubMed Central

Pelc, Karine; Cheron, Guy; Dan, Bernard

2008-01-01

Angelman syndrome has been suggested as a disease model of neurogenetic developmental condition with a specific behavioral phenotype. It is due to lack of expression of the UBE3A gene, an imprinted gene located on chromosome 15q. Here we review the main features of this phenotype, characterized by happy demeanor with prominent smiling, poorly specific laughing and general exuberance, associated with hypermotor behavior, stereotypies, and reduced behavioral adaptive skills despite proactive social contact. All these phenotypic characteristics are currently difficult to quantify and have been subject to some differences in interpretation. For example, prevalence of autistic disorder is still debated. Many of these features may occur in other syndromic or nonsyndromic forms of severe intellectual disability, but their combination, with particularly prominent laughter and smiling may be specific of Angelman syndrome. Management of problematic behaviors is primarily based on behavioral approaches, though psychoactive medication (eg, neuroleptics or antidepressants) may be required. PMID:18830393

Observations on the therapeutic practices of riverine communities of the Unini River, AM, Brazil.

PubMed

Santos, Juliana de Faria Lima; Pagani, Eduardo; Ramos, José; Rodrigues, Eliana

2012-07-13

Parts and products of animals and plants, like exudates, have been used for medicinal and/or toxic purposes by various human groups throughout history. However, few ethnopharmacological studies have engaged their rescue. To perform a broad ethnopharmacological survey of the local medicine practiced by traditional healing experts living in relative isolation at seven communities within the Amazon rainforest, in order to provide the basis for further pharmacological studies of the most promising findings. The field work was conducted using an ethnographic approach with the assistance of a doctor. Plants and animals, as well as their products and derivatives, reported by the practitioners as being involved in healing practices were collected, identified and deposited in scientific collections. A total of 33 traditional healing experts were selected and interviewed; they described themselves as: healer, midwife, knowledgeable of natural drugs or 'desmintidor' (an expert in massage techniques for the treatment of muscle contractures and joint sprains). In this therapeutic practice, 122 plant species, belonging to 60 botanical families, were indicated and collected; the most frequently mentioned families were: Fabaceae s.l. (10%), Arecaceae (6%), Zingiberaceae (5%) and Lamiaceae (5%). Plant exudates from 14 of those plant species were also indicated and collected, with those from the Burseraceae family being the most common. Furthermore, 57 animals belonging to 35 taxonomic families were indicated. They most frequently belonged to 2 families of bony fishes: Cichlidae (14%) and Characidae (9%). Plants and animals were indicated for 67 therapeutic uses and grouped into 21 usage categories; the psychoactive category was associated with the greatest number of used resources (17%), followed by the cultural syndromes category (16.7%). The geographic isolation and limited access to medical care in these communities resulted in unique, rich and consistent therapeutic system. There was a high degree of agreement among interviewees regarding the use of the same resources especially in the categories: psychoactive, cultural syndromes, pregnancy and childbirth, and inflammatory processes, suggesting a high degree of repetition and intercommunication. Further pharmacological and phytochemical investigations may search for new bioactive compounds among the described resources. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Determination of 74 new psychoactive substances in serum using automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry.

PubMed

Lehmann, Sabrina; Kieliba, Tobias; Beike, Justus; Thevis, Mario; Mercer-Chalmers-Bender, Katja

2017-10-01

A detailed description is given of the development and validation of a fully automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method capable of detecting 90 central-stimulating new psychoactive substances (NPS) and 5 conventional amphetamine-type stimulants (amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-N-ethyl-amphetamine (MDEA), methamphetamine) in serum. The aim was to apply the validated method to forensic samples. The preparation of 150μL of serum was performed by an Instrument Top Sample Preparation (ITSP)-SPE with mixed mode cation exchanger cartridges. The extracts were directly injected into an LC-MS/MS system, using a biphenyl column and gradient elution with 2mM ammonium formate/0.1% formic acid and acetonitrile/0.1% formic acid as mobile phases. The chromatographic run time amounts to 9.3min (including re-equilibration). The total cycle time is 11min, due to the interlacing between sample preparation and analysis. The method was fully validated using 69 NPS and five conventional amphetamine-type stimulants, according to the guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh). The guidelines were fully achieved for 62 analytes (with a limit of detection (LOD) between 0.2 and 4μg/L), whilst full validation was not feasible for the remaining 12 analytes. For the fully validated analytes, the method achieved linearity in the 5μg/L (lower limit of quantification, LLOQ) to 250μg/L range (coefficients of determination>0.99). Recoveries for 69 of these compounds were greater than 50%, with relative standard deviations≤15%. The validated method was then tested for its capability in detecting a further 21 NPS, thus totalling 95 tested substances. An LOD between 0.4 and 1.6μg/L was obtained for these 21 additional qualitatively-measured substances. The method was subsequently successfully applied to 28 specimens from routine forensic case work, of which 7 samples were determined to be positive for NPS consumption. Copyright © 2017 Elsevier B.V. All rights reserved.

Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species.

PubMed

Hatipoglu, Seda Damla; Yalcinkaya, Burhanettin; Akgoz, Muslum; Ozturk, Turan; Goren, Ahmet C; Topcu, Gulacti

2017-11-01

Salvia, an important and widely available member of Lamiaceae family. Although comparative analysis on secondary metabolites in several Salvia species from Turkey has been reported, their hallucinogenic chemicals have not been screened thoroughly. This study provides LC-MS/MS analysis of 40 Salvia species for screening their psychoactive constituents of salvinorin A and salvinorin B. 5S-rRNA gene non-coding region of Salvia plants was sequenced, aligned and compared with that sequence of Salvia divinorum plant. Targeted molecules of salvinorin A and salvinorin B were quantified, using LC-MS/MS, from all aerial parts of 40 Salvia species, collected from different parts of Turkey. Regions of 5S-rRNA gene from different species were amplified by polymerase chain reaction and DNA sequences were aligned with Salvia divinorum DNA sequences. Very few of the Salvia species (S. recognita, S. cryptantha and S. glutinosa) contained relatively high levels of salvinorin A (212.86 ± 20.46 μg/g, 51.50 ± 4.95 μg/g and 38.92 ± 3.74 μg/g, respectively). Salvinorin B was also found in Salvia species of S. potentillifolia, S. adenocaulon and S. cryptantha as 2351.99 ± 232.22 μg/g, 768.78 ± 75.90 μg/g and 402.24 ± 39.71 μg/g, respectively. The sequences of 5S-rRNA gene of 40 different Salvia species were presented and it was found that none of the Salvia species in Turkey had similar DNA sequence to Salvia divinorum plant. This is the first report of screening 40 Salvia species in Turkey according to their psychoactive constituents, salvinorin A and salvinorin B and their genomic structures. It is possible that some of these Salvia species may exhibit some psycho activity. Thus, they need to be screened further. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

PubMed Central

PACHER, PÁL; BÁTKAI, SÁNDOR; KUNOS, GEORGE

2008-01-01

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients’ need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy. PMID:16968947

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

[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.

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.

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.

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

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.