Classic hallucinogens in the treatment of addictions.

PubMed

Bogenschutz, Michael P; Johnson, Matthew W

2016-01-04

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic compounds.

PubMed

Neelkantan, Nikhil; Mikhaylova, Alina; Stewart, Adam Michael; Arnold, Raymond; Gjeloshi, Visar; Kondaveeti, Divya; Poudel, Manoj K; Kalueff, Allan V

2013-08-21

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish ( Danio rerio ) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans.

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

PubMed Central

2013-01-01

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs’ action. The utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans. PMID:23883191

Clinical applications of hallucinogens: A review.

PubMed

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H

2016-08-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Clinical Applications of Hallucinogens: A Review

PubMed Central

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H.

2016-01-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. PMID:27454674

Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines.

PubMed

Winter, J C

2009-04-01

Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species. The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine. The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT(2A) receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT(2C) and 5-HT(1A) receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities. Hallucinogen-induced stimulus control provides a unique behavioral tool for the

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.

The hallucinogenic world of tryptamines: an updated review.

PubMed

Araújo, Ana Margarida; Carvalho, Félix; Bastos, Maria de Lourdes; Guedes de Pinho, Paula; Carvalho, Márcia

2015-08-01

In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT), present in South American psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. However, with the discovery of hallucinogenic properties of lysergic acid diethylamide (LSD) in mid-1900s, tryptamines began to be used recreationally among young people. More recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (AMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace LSD ('legal' alternatives to LSD). Tryptamine derivatives are widely accessible over the Internet through companies selling them as 'research chemicals', but can also be sold in 'headshops' and street dealers. Reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. However, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. This review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.

The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

PubMed

Butelman, Eduardo R; Rus, Szymon; Prisinzano, Thomas E; Kreek, Mary Jeanne

2010-06-01

The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives

PubMed Central

Martinotti, Giovanni; Spano, Maria Chiara; Lorusso, Marco; di Giannantonio, Massimo; Lerner, Arturo G.

2018-01-01

Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD. PMID:29547576

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

Hallucinogenic plant poisoning in children.

PubMed

Al-Shaikh, Adnan M; Sablay, Zakira M

2005-01-01

Datura is a hallucinogenic plant found in urban or rural areas in the Kingdom of Saudi Arabia KSA. It grows wildly in many parts of the country. Its taste and shape makes it unattractive to both man and animals, though deliberate use by young adults for its hallucinogenic effects have been widely reported for the past 30 years. Datura contains 3 main toxic alkaloids: atropine, scopolamine and hyoscamine. Consumption of any part of the plant can result in severe anticholinergic toxicity. Clinical symptoms are those seen in atropine poisoning, particularly mydriasis and hallucinations. Children have a special susceptibility to atropine toxicity; even small amount may produce central nervous system manifestations. Hospitalization is required for agitation and combative behavior although symptomatic treatment is usually sufficient. We report a case of acute Datura stramonium intoxication in a 6-year-old boy from Khamis Mushayt, KSA, who presented with restlessness, hallucinations and mydriasis 8 hours after ingesting the seeds of Datura plant.

PCP and hallucinogens.

PubMed

Carroll, M E

1990-01-01

In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

Hallucinogen persisting perception disorder after psilocybin consumption: a case study.

PubMed

Espiard, Marie-Laure; Lecardeur, Laurent; Abadie, Pascale; Halbecq, Isabelle; Dollfus, Sonia

2005-08-01

The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described.

[Hallucinogenic fungi (psilocybe). Part II. Identification of Psilocybe semilanceata by PCR].

PubMed

Adamczyk, Aldona; Sadakierska-Chudy, Anna; Janoszka, Jerzy; Rymkiewicz, Apoloniusz; Dobosz, Tadeusz

2007-01-01

Psilocybe semilanceata belongs to the genus of Psilocybe; it is a hallucinogenic fungus, frequently found in regions with high rainfall, in the grass and moss. There are estimated to be as many as eight Psilocybe hallucinogenic species containing psychoactive alkaloids, such as psilocybin and psilocin, which may cause visual, auditory and other hallucinations, as well as profound changes in the perception of time and space. Since identification of P semilanceata in a form different than a fresh mushroom is almost impossible, the authors made an attempt at developing a method of fungi identification based on the PCR technique, which could be helpful in a fight against dangerous consumption of these hallucinogens by the youth. Detection of the specific DNA sequence for P semilanceata brought good results; the test may be commonly employed in forensic practice in the future.

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens.

PubMed

Goda, Sailaja A; Piasecka, Joanna; Olszewski, Maciej; Kasicki, Stefan; Hunt, Mark J

2013-07-01

The nucleus accumbens (NAc) is a site critical for the actions of many drugs of abuse. Psychoactive compounds, such as N-methyl-D-aspartate receptor (NMDAR) antagonists, modify gamma (40-90) and high frequency oscillations (HFO, 130-180 Hz) in local field potentials (LFPs) recorded in the NAc. Lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI) are serotonergic hallucinogens and activation of 5HT2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear. This study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed. LFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally. LSD (0.03-0.3 mg/kg) and DOI (0.5-2.0 mg/kg) increased the power and reduced the frequency of HFO. In contrast, the hallucinogens produced a robust reduction in the power of low (40-60 Hz), but not high gamma oscillations (70-90 Hz). MDL 11939 (1.0 mg/kg), a 5HT2A receptor antagonist, fully reversed the changes induced by DOI on HFO but only partially for the low gamma band. Equivalent increases in HFO power were observed after TCB-2 (5HT2A receptor agonist, 0.1-1.5 mg/kg), but not CP 809101 (5H2C receptor agonist, 0.1-3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg). Serotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.

[The ethnopharmacology of hallucinogens: from "primitive rites" to their "presence" on TV. Proposals for the year 2000].

PubMed

Cugurra, F

1996-11-01

Hallucinogens are the chemicals which in nontoxic doses produce changes in perception, mental confusion, memory loss, or disorientation for person, place and time, with organic brain reactions. Mescaline and LSD are historically the most interesting hallucinogens. Today the cannabis is very important, socially. Traditional hallucinogens survive everywhere in the world. A dramatic increase in use of cartoons in drug education and prevention programs prove great damages: in comics and films often have stimulated the appetite for drug experimentation (seduction of innocent, R. K. Siegel). Cartoons and comics are instruments for correcting perceptions and behaviour of youth and youthful drug abusers. As the hallucinogens.

Researchers Explore New Visions for Hallucinogens

ERIC Educational Resources Information Center

Brown, Susan

2006-01-01

Recently, 36 people who had never taken hallucinogens before gave them a try. The pill they took launched a daylong psychedelic journey, sometimes fantastic, sometimes frightening. When it was over, a few who took the drug said it was the most meaningful experience of their lives, as momentous as the birth of a first child or the death of a…

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

North American Indian rock art and hallucinogenic drugs.

PubMed

Wellmann, K F

1978-04-14

It is proposed that the aboriginal rock paintings in two areas of North America may have been produced by shamans while they were under the influence of hallucinogenic agents derived from plants. The first of these areas is the Chumash and Yokuts Indian region of California, where polychrome paintings show designs similar to those visualized during the trance induced by decoctions of jimsonweed (Datura species). The second area is the lower Pecos River region of Texas, where shamanistic figures display traits considered to be conceptual analogues of the mescal bean (Sophora secundiflora) cult as practiced during historic times by Great Plains Indians. Although the evidence is only circumstantial, the proposed connections between these rock drawings and mind-expanding pharmacologic compounds fit well into the documented relationship that encompasses hallucinogenic drugs and certain movable objects of pre-Columbian American art.

An item response theory analysis of DSM-IV criteria for hallucinogen abuse and dependence in adolescents

PubMed Central

Wu, Li-Tzy; Pan, Jeng-Jong; Yang, Chongming; Reeve, Bryce B.; Blazer, Dan G.

2009-01-01

Aim This study applied both item response theory (IRT) and multiple indicators–multiple causes (MIMIC) methods to evaluate item-level psychometric properties of diagnostic questions for hallucinogen use disorders (HUDs), differential item functioning (DIF), and predictors of latent HUD. Methods Data were drawn from 2004–2006 National Surveys on Drug Use and Health. Analyses were based on 1548 past-year hallucinogen users aged 12–17 years. Substance use and symptoms were assessed by audio computer-assisted self-interviewing methods. Results Abuse and dependence criteria empirically were arrayed along a single continuum of severity. All abuse criteria indicated middle-to-high severity on the IRT-defined HUD continuum, while dependence criteria captured a wider range from the lowest (tolerance and time spent) to the highest (taking larger amounts and inability to cut down) severity levels. There was indication of DIF by hallucinogen users’ age, gender, race/ethnicity, and ecstasy use status. Adjusting for DIF, ecstasy users (vs. non-ecstasy hallucinogen users), females (vs. males), and whites (vs. Hispanics) exhibited increased odds of HUD. Conclusions Symptoms of hallucinogen abuse and dependence empirically do not reflect two discrete conditions in adolescents. Trends and problems related to hallucinogen use among girls and whites should be examined further to inform the designs of effective gender-appropriate and culturally sensitive prevention programs. PMID:19896773

A proposal to evaluate mechanistic efficacy of hallucinogens in addiction treatment.

PubMed

Burdick, Brittany Vasae; Adinoff, Bryon

2013-09-01

Current treatments for addiction are frequently ineffective. Hallucinogenic therapy has been indicated as helpful for a range of substance use disorders, yet this approach remains understudied and publicly unavailable. It is nonetheless a promising treatment, which has significant, long-term beneficial effects with single doses and a profile characterized by general safety, low toxicity, and non-addictiveness. However, pharmacological interventions, such as hallucinogens, should not be offered if the same effects (e.g. psychological insights/mystical experiences) and outcomes (e.g. decreased drug use) could be achieved absent pharmacological intervention. To date, there have been no clinical comparisons of drug-induced altered states with non-drug-induced states for addiction treatment. We propose and then outline a clinical trial to address this gap in knowledge. The proposed design would evaluate abstinence outcomes in a population of prescription opioid abusers after exposure to one of three conditions: a drug-induced altered state using psilocybin, a non-drug-induced altered state via hyperventilation (Holotropic Breathwork), and an active placebo with niacin. The outcomes of such a study would reveal important differences in therapeutic potential by discriminating hallucinogen-dependent effects from those psychological effects resulting from altered states.

Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses.

PubMed

Bogenschutz, Michael P; Pommy, Jessica M

2012-01-01

Alcohol and drug addiction are major public health problems, and existing treatments are only moderately effective. Although there has been interest for over half a century in the therapeutic use of classic hallucinogens to treat addictions, clinical research with these drugs was halted at an early stage in the early 1970s, leaving many fundamental questions unanswered. In the past two decades, clinical research on classic hallucinogens has resumed, although addiction treatment trials are only now beginning. The purpose of this paper is to provide a targeted review of the research most relevant to the therapeutic potential of hallucinogens, and to integrate this information with current thinking about addiction and recovery. On the basis of this information, we present a heuristic model which organizes a number of hypotheses that may be tested in future research. We conclude that existing evidence provides a convincing rationale for further research on the effects of classic hallucinogens in the treatment of addiction. Copyright © 2012 John Wiley & Sons, Ltd.

Hallucinogenic Drug Research: Impact on Science and Society.

ERIC Educational Resources Information Center

Gamage, James R.; Zerkin, Edmund L., Ed.

This book, authored by experienced researchers in the hallucinogenic drug field, is intended to fill the gap created by most previously published work, which tends to be either highly technical or emotional and partisan. The authors range from ardent proponents to skeptics, but they share a commitment to scientific evidence and the clear…

Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use.

PubMed

Walsh, Zach; Hendricks, Peter S; Smith, Stephanie; Kosson, David S; Thiessen, Michelle S; Lucas, Philippe; Swogger, Marc T

2016-07-01

Evidence suggests that hallucinogens may have therapeutic potential for addressing a variety of problem behaviors related to the externalizing spectrum of psychopathology, such as substance misuse and criminality. Intimate partner violence (IPV) is a prevalent form of criminal violence that is related to externalizing pathology. However, the association between hallucinogen use and IPV has not been comprehensively examined. In this prospective study, we examined the association between IPV and naturalistic hallucinogen use among 302 inmates at a US county jail. Cox regression analyses indicated that hallucinogen use predicted reduced arrest for IPV independently (β=-0.54, SE=0.20, χ(2)=7.19, exp(B)=0.58, p<0.01) and after accounting for covariates (β=-0.48, SE=0.23, χ(2)=4.44, exp(B)=0.62, p<0.05). These results add to a growing literature suggesting distinct therapeutic potential for hallucinogens to assist in the attenuation of problematic behavior. © The Author(s) 2016.

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

PubMed

Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

2013-03-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

PubMed Central

Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

2013-01-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey.

PubMed

Schindler, Emmanuelle A D; Gottschalk, Christopher H; Weil, Marsha J; Shapiro, Robert E; Wright, Douglas A; Sewell, Richard Andrew

2015-01-01

Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.

A regulatory perspective on the evaluation of hallucinogen drugs for human use.

PubMed

Calderon, Silvia N; Hunt, Joshua; Klein, Michael

2017-11-24

In recent years, there is renewed interest in the study of various hallucinogens for their potential therapeutic effects. In the United States of America (USA), the abuse potential assessment of a drug is carried out as part of the general safety and efficacy evaluation of a drug. Additionally, the abuse potential assessment is taken under consideration in determining if a drug needs to be subject to controls to minimize the abuse of the drug once on the market. This assessment is conducted for all new drugs with central nervous system (CNS) activity, that are chemically or pharmacologically similar to other drugs with known abuse potential, or drugs that produce psychoactive effects predictive of abuse, such as euphoria and hallucinations. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, with emphasis on hallucinogens. The paper discusses the role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs and its role in drug control, and provides an overview of the controlled status of hallucinogens and the requirements to conduct research with Schedule I substances in the USA. Published by Elsevier Ltd.

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens.

PubMed

Canal, Clinton E; Murnane, Kevin S

2017-01-01

Classic hallucinogens share pharmacology as serotonin 5-HT 2A , 5-HT 2B , and 5-HT 2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT 2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT 2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area-nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT 2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT 2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens.

Quantitative Phosphoproteomics Unravels Biased Phosphorylation of Serotonin 2A Receptor at Ser280 by Hallucinogenic versus Nonhallucinogenic Agonists*

PubMed Central

Karaki, Samah; Becamel, Carine; Murat, Samy; Mannoury la Cour, Clotilde; Millan, Mark J.; Prézeau, Laurent; Bockaert, Joël; Marin, Philippe; Vandermoere, Franck

2014-01-01

The serotonin 5-HT2A receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. An incompletely resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and activity lack such a psychoactive activity. Using a strategy combining stable isotope labeling by amino acids in cell culture with enrichment in phosphorylated peptides by means of hydrophilic interaction liquid chromatography followed by immobilized metal affinity chromatography, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor and exposed to either vehicle or the synthetic hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) or the nonhallucinogenic 5-HT2A agonist lisuride. Among the 5995 identified phosphorylated peptides, 16 sites were differentially phosphorylated upon exposure of cells to DOI versus lisuride. These include a serine (Ser280) located in the third intracellular loop of the 5-HT2A receptor, a region important for its desensitization. The specific phosphorylation of Ser280 by hallucinogens was further validated by quantitative mass spectrometry analysis of immunopurified receptor digests and by Western blotting using a phosphosite specific antibody. The administration of DOI, but not of lisuride, to mice, enhanced the phosphorylation of 5-HT2A receptors at Ser280 in the prefrontal cortex. Moreover, hallucinogens induced a less pronounced desensitization of receptor-operated signaling in HEK-293 cells and neurons than did nonhallucinogenic agonists. The mutation of Ser280 to aspartic acid (to mimic phosphorylation) reduced receptor desensitization by nonhallucinogenic agonists, whereas its mutation to alanine increased the ability of hallucinogens to desensitize the receptor. This study reveals a biased phosphorylation of

Identification of hallucinogenic fungi from the genera Psilocybe and Panaeolus by amplified fragment length polymorphism.

PubMed

Lee, J C; Cole, M; Linacre, A

2000-05-01

Unambiguous identification of the hallucinogenic fungi of the genera Psilocybe and Panaeolus is required by national and international drug control legislation. We report on a DNA-based test using the technique of amplified fragment length polymorphism (AFLP). AFLP can differentiate species of the two genera Psilocybe and Panaeolus by using different primer sets. The identification of hallucinogenic fungi using a DNA-based test, which can be used in conjunction with morphological features, will assist in forensic investigations.

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

PubMed Central

Canal, Clinton E; Murnane, Kevin S

2017-01-01

Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area—nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens. PMID:27903793

High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

PubMed Central

Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

2013-01-01

Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

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.

Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.

PubMed

Halberstadt, Adam L; Powell, Susan B; Geyer, Mark A

2013-07-01

The 5-HT₂A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT₂A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT₂A/₂C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT₂A knockout mice, indicating the effect is a consequence of 5-HT₂A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT₂A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT₂A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT₂A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT₂A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT₂A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5

[Microscopic study of powders of hallucinogenic mushrooms--Psilocybe sp].

PubMed

Schäfer, A T

2000-01-01

The paper presents simple methods for microscopic examination and basic microchemical testing for the identification of suspect mushroom powders. The microscopic features of the most commonly cultivated and trafficked hallucinogenic genus Psilocybin are described and may serve for the decision whether any suspect material consists of such mushroom powder (and is therefore to be subjected to further analysis) or not.

Factor Analysis of the Mystical Experience Questionnaire: A Study of Experiences Occasioned by the Hallucinogen Psilocybin

PubMed Central

Maclean, Katherine A.; Leoutsakos, Jeannie-Marie S.; Johnson, Matthew W.; Griffiths, Roland R.

2012-01-01

A large body of historical evidence describes the use of hallucinogenic compounds, such as psilocybin mushrooms, for religious purposes. But few scientific studies have attempted to measure or characterize hallucinogen-occasioned spiritual experiences. The present study examined the factor structure of the Mystical Experience Questionnaire (MEQ), a self-report measure that has been used to assess the effects of hallucinogens in laboratory studies. Participants (N=1602) completed the 43-item MEQ in reference to a mystical or profound experience they had had after ingesting psilocybin. Exploratory factor analysis of the MEQ retained 30 items and revealed a 4-factor structure covering the dimensions of classic mystical experience: unity, noetic quality, sacredness (F1); positive mood (F2); transcendence of time/space (F3); and ineffability (F4). MEQ factor scores showed good internal reliability and correlated with the Hood Mysticism Scale, indicating convergent validity. Participants who endorsed having had a mystical experience on psilocybin, compared to those who did not, had significantly higher factor scores, indicating construct validity. The 4-factor structure was confirmed in a second sample (N=440) and demonstrated superior fit compared to alternative models. The results provide initial evidence of the validity, reliability, and factor structure of a 30-item scale for measuring single, hallucinogen-occasioned mystical experiences, which may be a useful tool in the scientific study of mysticism. PMID:23316089

Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin.

PubMed

Bogenschutz, Michael P

2013-03-01

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists

PubMed Central

Moreno, José L.; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C.; González-Maeso, Javier

2011-01-01

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [3H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. PMID:21276828

Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

PubMed Central

Halberstadt, Adam L.; Powell, Susan B.; Geyer, Mark A.

2014-01-01

The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and

Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor.

PubMed

Benekareddy, Madhurima; Nair, Amrita R; Dias, Brian G; Suri, Deepika; Autry, Anita E; Monteggia, Lisa M; Vaidya, Vidita A

2013-03-01

Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity. We sought to examine whether trophic factor signalling through brain-derived neurotrophic factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response to distinct stimuli such as immobilization stress and the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the neocortex led to a robust up-regulation of local Arc transcript expression. Further, baseline Arc mRNA expression in the neocortex was significantly decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific BDNF loss. The induction of Arc mRNA levels in response to both acute immobilization stress or a single administration of DOI was significantly attenuated in the inducible BDNF knockout mice. Taken together, our results implicate trophic factor signalling through BDNF in the regulation of cortical Arc mRNA expression, both under baseline conditions and following stress and hallucinogen exposure. These findings suggest the possibility that the regulation of Arc expression via BDNF provides a molecular substrate for the structural and synaptic plasticity observed following stimuli such as stress and hallucinogens.

Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.

PubMed

Smith, Douglas A; Bailey, Jessica M; Williams, Diarria; Fantegrossi, William E

2014-12-01

The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

PubMed Central

Smith, Douglas A.; Bailey, Jessica M.; Williams, Diarria

2014-01-01

The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. PMID:25271256

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.

PubMed

Moreno, José L; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C; González-Maeso, Javier

2011-04-15

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [(3)H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A survey of hallucinogenic mushroom use, factors related to usage, and perceptions of use among college students.

PubMed

Hallock, Robert M; Dean, Andrew; Knecht, Zachary A; Spencer, Jared; Taverna, Elise C

2013-06-01

Recreational usage and attitudes toward psilocybin-containing hallucinogenic mushrooms among college students are seldom explored. We surveyed 882 randomly selected undergraduates at Skidmore College in upstate New York and quantified whether participants had ever used psilocybin mushrooms, their attitudes toward the drug, and polydrug use. There were 409 responses and 29.5% of the sample reported psilocybin use. Among users, the mean number of times they reported using mushrooms was 3.4 (mode=1). The top factors cited that influenced their decisions to try hallucinogenic mushrooms for the first time were 'curiosity', 'to achieve a mystical experience', and 'introspection'. Users and non-users had significantly different perceptions of mushrooms: non-users were more likely to say that hallucinogenic mushrooms were addictive and had the potential for abuse than users. Users did not believe that psilocybin negatively impacts their academics, mental health, or physical health, while non-users did. Both users and non-users of psilocybin reported high life-time use of alcohol (97% vs 96%, respectively), marijuana (98% vs 73%, respectively) and tobacco (82% vs 54%, respectively). Psilocybin users were significantly more likely to use other drugs such as cocaine, ecstasy, opiates, non-prescribed prescription drugs, opiates, and lysergic acid diethylamide (LSD) than non-users of psilocybin. This study uncovers important insights into hallucinogenic mushroom use by college students. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money and Finance REGULATIONS GOVERNING CONDUCT IN OR ON THE BUREAU OF THE MINT BUILDINGS AND GROUNDS § 91.8...

Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model

PubMed Central

Canal, Clint E.; Morgan, Drake

2013-01-01

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals. PMID:22517680

Personality Characteristics of Adolescents with Hallucinogen, Methamphetamine, and Cannabis Dependence: A Comparative Study

ERIC Educational Resources Information Center

Palmer, Glen A.; Daiss, Doyle D.

2005-01-01

A comparison of personality factors on scales of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) was conducted with a sample of adolescents referred to a residential substance abuse treatment program. A total of sixty adolescents identified with hallucinogen (n = 20), cannabis (n = 20), or methamphetamine (n = 20) as their drug…

Forensic analysis of hallucinogenic mushrooms and khat (Catha edulis Forsk) using cation-exchange liquid chromatography.

PubMed

Laussmann, Tim; Meier-Giebing, Sigrid

2010-02-25

Hallucinogenic mushrooms (e.g. Psilocybe and Panaeolus species) as well as leaves and young shoots of the khat tree (Catha edulis Forsk) are illicit drugs in many countries. The exact concentration of the hallucinogenic alkaloids psilocin and psilocybin in mushrooms and the sympathomimetic alkaloids cathinone and cathine in khat is usually essential for jurisdiction. Facing an increasing number of mushroom and khat seizures by German customs authorities, a convenient comprehensive quantitative HPLC method based on cation-exchange liquid chromatography for these rather "exotic" drugs has been developed which avoids time-consuming multi-step sample preparation or chemical derivatization procedures. Using this method a number of different hallucinogenic fungi species and products that are mainly distributed via the internet have been analysed (dried and fresh Psilocybe cubensis Singer as well as P. cubensis collected from "grow boxes", Panaeolus cyanescens Berkeley and Broome and so-called "philosopher stones" (sclerotia of Psilocybe species)). Highest total amounts of psilocin have been detected in dried P. cyanescens reaching up to 3.00+/-0.24 mg per 100 mg. The distribution of khat alkaloids in different parts of the khat shoots has been studied. High concentrations of cathinone have not only been detected in leaves but also in green parts and barks of stalks. Additionally, the sample treatment for fresh mushroom and khat samples has been optimised. Highest amounts of alkaloids were found when fresh material was freeze-dried. 2009 Elsevier Ireland Ltd. All rights reserved.

Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens.

PubMed

Bouso, José Carlos; Pedrero-Pérez, Eduardo José; Gandy, Sam; Alcázar-Córcoles, Miguel Ángel

2016-09-01

In the present study we explored the psychometric properties of three widely used questionnaires to assess the subjective effects of hallucinogens: the Hallucinogen Rating Scale (HRS), the Mystical Experience Questionnaire (MEQ), and the Addiction Research Center Inventory (ARCI). These three questionnaires were administered to a sample of 158 subjects (100 men) after taking ayahuasca, a hallucinogen whose main active component is N,N-dimethyltryptamine (DMT). A confirmatory factorial study was conducted to check the adjustment of previous data obtained via theoretical proposals. When this was not possible, we used an exploratory factor analysis without restrictions, based on tetrachoric and polychoric matrices and correlations. Our results sparsely match the theoretical proposals of the authors, perhaps because previous studies have not always employed psychometric methods appropriate to the data obtained. However, these data should be considered preliminary, pending larger samples to confirm or reject the proposed structures obtained. It is crucial that instruments of sufficiently precise measurement are utilized to make sense of the information obtained in the study of the subjective effects of psychedelic drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Aeruginascin, a trimethylammonium analogue of psilocybin from the hallucinogenic mushroom Inocybe aeruginascens.

PubMed

Jensen, Niels; Gartz, Jochen; Laatsch, Hartmut

2006-06-01

The hallucinogenic mushroom Inocybe aeruginascens contains several typical Psilocybe alkaloids including psilocybin. We have now elucidated the structure of a further indole derivative named aeruginascin as the quaternary ammonium compound N, N, N-trimethyl-4-phosphoryloxytryptamine. Aeruginascin is closely related to the frog skin toxin bufotenidine (5-HTQ), a potent 5-HT3 receptor agonist, and has been found exclusively in Inocybe aeruginascens so far.

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents.

PubMed

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

2017-08-01

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74-78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

PubMed

Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R

2011-05-01

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.

PubMed

Carbonaro, Theresa M; Johnson, Matthew W; Hurwitz, Ethan; Griffiths, Roland R

2018-02-01

Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness

PubMed Central

MacLean, Katherine A.; Johnson, Matthew W.; Griffiths, Roland R.

2012-01-01

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than one year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change. PMID:21956378

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.

PubMed

MacLean, Katherine A; Johnson, Matthew W; Griffiths, Roland R

2011-11-01

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

Hallucinogenic mushrooms on the German market - simple instructions for examination and identification.

PubMed

Musshoff, F; Madea, B; Beike, J

2000-09-11

'Magic mushrooms' is the name most commonly given to psychoactive fungi containing the hallucinogenic components psilocybin and psilocin. Material confiscated by local authorities was examined using morphologic, microscopic, microchemical, and toxicological methods. Psilocybe cubensis was the most popular mushroom in the sample collective, followed by Psilocybe semilanceata, Panaeolus cyanescens and Psilocybe tampanensis. The alkaloid content was determined with <0.003-1.15% of psilocybin and 0.01-0.90% psilocin. Panaeolus cyanescens was the mushroom with highest levels of psilocybin and psilocin.

Classification and Short-Term Course of DSM-IV Cannabis, Hallucinogen, Cocaine, and Opioid Disorders in Treated Adolescents

ERIC Educational Resources Information Center

Chung, Tammy; Martin, Christoper S.

2005-01-01

This study examined the latent class structure of Diagnostic and Statistical Manual of Mental Disorders (text rev.; DSM-IV; American Psychiatric Association, 2000) symptoms used to diagnose cannabis, hallucinogen, cocaine, and opiate disorders among 501 adolescents recruited from addictions treatment. Latent class results were compared with the…

IS THE U.S. EXPERIENCING AN INCIPIENT EPIDEMIC OF HALLUCINOGEN USE?

PubMed Central

Golub, Andrew; Johnson, Bruce D.; Sifaneck, Stephen J.; Chesluk, Benjamin; Parker, Howard

2008-01-01

NHSDA and MTF survey data indicate “epidemic”-like growth in hallucinogen use from 1992-1996 and associated increases in cocaine, crack, heroin and amphetamine use. These trends might have resulted from a proliferation of raves and dance clubs in the U.S. as occurred in Europe and elsewhere, although in contrast to evidence regarding European experiences the American epidemic involves primarily teens as opposed to persons in their twenties and involves primarily use of LSD as opposed to MDMA. This analysis highlights the need for further research into the context, significance, and consequences of these recently popular American drug use practices. PMID:11758819

Dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria: implications for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

PubMed

Kerridge, Bradley T; Saha, Tulshi D; Smith, Sharon; Chou, Patricia S; Pickering, Roger P; Huang, Boji; Ruan, June W; Pulay, Attila J

2011-09-01

Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM-IV currently lacking empirical justification. Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse

Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement.

PubMed

Halberstadt, Adam L; Geyer, Mark A

2013-06-01

The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT2A agonists. The HTR is widely used as a behavioral assay for 5-HT2A activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice. Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response. Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean head movement frequency of 90.3 Hz). Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response. The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25, 0.5, and 1.0 mg/kg, i.p.) and lysergic acid diethylamide (LSD; 0.05, 0.1, 0.2, and 0.4 mg/kg, i.p.) with extremely high sensitivity and specificity. Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2.5 and 5.0 mg/kg, i.p.) and lisuride (0.8, 1.6, and 3.2 mg/kg, i.p.) did not induce the HTR. These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens. The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods.

Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement

PubMed Central

Halberstadt, Adam L.; Geyer, Mark A.

2013-01-01

Rationale The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT2A agonists. The HTR is widely used as a behavioral assay for 5-HT2A activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. Objective High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice. Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response. Results Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean reciprocation frequency of 90.3 Hz). Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response. The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25, 0.5, and 1.0 mg/kg, IP) and lysergic acid diethylamide (LSD; 0.05, 0.1, 0.2, and 0.4 mg/kg, IP) with extremely high sensitivity and specificity. Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2.5 and 5.0 mg/kg, IP) and lisuride (0.8, 1.6, and 3.2 mg/kg, IP) did not induce the HTR. Conclusions These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens. The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods. PMID:23407781

Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies.

PubMed

Ross, Stephen

2012-06-01

Only time will tell if serotonergic hallucinogen-assisted psychotherapy treatment paradigms for SUDs will prove to be safe and effective in double-blind, placebo-controlled clinical trials. If they are, they would truly constitute a novel psychopharmacologic-psychosocial treatment paradigm to treat addictive disorders, although the risk of adverse psychological events would have to be controlled through a careful screening process and the risk of misuse of the substances or developing use syndromes would have to be considered, although the overall risk would be low because, as mentioned, SHs are unlike all other drugs of abuse in that they do not appear to produce dependence syndromes. There effects on the NA and DA range from inhibition to slight activation, all this without producing addiction. The ability of these medicinal tools to treat a range of addictive, psychiatric, and existential disorders is remarkable in scope and possibility. They truly represent a potential paradigmatic shift within the field of psychiatry, too interesting to not explore further.

Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey.

PubMed

Schneider, Ricardo; Ottoni, Gustavo L; de Carvalho, Hudson W; Elisabetsky, Elaine; Lara, Diogo R

2015-01-01

To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. The sample consisted of 8,646 individuals (24.7% men and 75.3% women) who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Temperament and Character Inventory - Revised (TCI-R), respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

Prefrontal cortical network activity: Opposite effects of psychedelic hallucinogens and D1/D5 dopamine receptor activation

PubMed Central

Lambe, Evelyn K.; Aghajanian, George K.

2007-01-01

The fine-tuning of network activity provides a modulating influence on how information is processed and interpreted in the brain. Here, we use brain slices of rat prefrontal cortex to study how recurrent network activity is affected by neuromodulators known to alter normal cortical function. We previously determined that glutamate spillover and stimulation of extrasynaptic NMDA receptors are required to support hallucinogen-induced cortical network activity. Since microdialysis studies suggest that psychedelic hallucinogens and dopamine D1/D5 receptor agonists have opposite effects on extracellular glutamate in prefrontal cortex, we hypothesized that these two families of psychoactive drugs would have opposite effects on cortical network activity. We found that network activity can be enhanced by DOI (a psychedelic hallucinogen that is a partial agonist of serotonin 5-HT2A/2C receptors) and suppressed by the selective D1/D5 agonist SKF 38393. This suppression could be mimicked by direct activation of adenylyl cyclase with forskolin or by addition of a cAMP analog. These findings are consistent with previous work showing that activation of adenylyl cyclase can upregulate neuronal glutamate transporters, thereby decreasing synaptic spillover of glutamate. Consistent with this hypothesis, a low concentration of the glutamate transporter inhibitor TBOA restored electrically-evoked recurrent activity in the presence of a selective D1/D5 agonist, whereas recurrent activity in the presence of a low level of the GABAA antagonist bicuculline was not resistant to suppression by the D1/D5 agonist. The tempering of network UP states by D1/D5 receptor activation may have implications for the proposed use of D1/D5 agonists in the treatment of schizophrenia. PMID:17293055

Hallucinogens and Dissociative Drugs, Including LSD, PCP, Ketamine, Dextromethorphan. National Institute on Drug Abuse Research Report Series.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

Research is developing a clearer picture of the dangers of mind-altering drugs. The goal of this report is to present the latest information to providers to help them strengthen their prevention and treatment efforts. A description is presented of dissociative drugs, and consideration is given as to why people take hallucinogens. The physical…

The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample.

PubMed

Lawn, Will; Barratt, Monica; Williams, Martin; Horne, Abi; Winstock, Adam

2014-08-01

The NBOMe compounds are a novel series of hallucinogenic drugs that are potent agonists of the 5-HT2A receptor, have a short history of human consumption and are available to buy online, in most countries. In this study, we sought to investigate the patterns of use, characteristics of users and self-reported effects. A cross-sectional anonymous online survey exploring the patterns of drug use was conducted in 2012 (n = 22,289), including questions about the use of 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of respondents (n = 582) reported having ever tried one of the three NBOMe drugs and that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and 81.2% of this group administered the drug orally or sublingually/buccally. Subjective effects were similar to comparison serotonergic hallucinogens, though higher 'negative effects while high' and greater 'value for money' were reported. The most common (41.7%) drug source was via a website. The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet. © The Author(s) 2014.

The effect of central nervous system depressant, stimulant and hallucinogenic drugs on injury severity in patients admitted for trauma.

PubMed

Cordovilla-Guardia, Sergio; Lardelli-Claret, Pablo; Vilar-López, Raquel; López-Espuela, Fidel; Guerrero-López, Francisco; Fernández-Mondéjar, Enrique

2017-08-04

The effect of drugs other than alcohol on severity of trauma remains unclear. Pooled data analyses in previous studies that grouped substances with opposite effects on the central nervous system (CNS) may have masked the influence of substances on injury severity. The aim was to analyze the effect of stimulant, hallucinogenic and depressant drugs other than alcohol on injury severity in trauma patients. The presence of alcohol, stimulant drugs (cocaine, amphetamines and methamphetamines), depressant drugs (benzodiazepines, opiates, methadone and barbiturates) and hallucinogenic drugs (THC and PCP) was analyzed in 1187 patients between 16 and 70 years old admitted to a trauma hospital between November 2012 and June 2015. Injury severity was determined prospectively as the Injury Severity Score. A multivariate analysis was used to quantify the strength of association between exposure to substances and trauma severity, using the presence of alcohol as a stratification variable. Drugs other than alcohol were found in 371 patients (31.3%): 32 (2.7%) stimulants, 186 (15.3%) depressants, 78 (6.6%) hallucinogenics and 75 (5.6%) polydrug use. The presence of CNS depressant substances was associated with increased injury severity only in patients also exposed to alcohol, with an adjusted odds ratio of 4.63 (1.37-15.60) for moderate injuries and 7.83 (2.53-24.21) for severe. CNS depressant drugs had a strong influence on injury severity in patients who screened positive for alcohol consumption. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Toxicities associated with NBOMe ingestion, a novel class of potent hallucinogens: A review of the literature

PubMed Central

Suzuki, Joji; Dekker, Michael A.; Valenti, Erin S.; Arbelo Cruz, Fabiola A.; Correa, Ady M.; Poklis, Justin L.; Poklis, Alphonse

2014-01-01

Objective A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion. Methods We searched the PubMed for relevant English language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted. Results Ten citations met criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analog identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Seven (35%) were discharged after a period of observation, while 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common laboratory abnormalities were elevated creatine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%). Conclusion NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens. PMID:25659919

Dimensionality of Hallucinogen and Inhalant/Solvent Abuse and Dependence Criteria: Implications for the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition

PubMed Central

Kerridge, Bradley T.; Saha, Tulshi D.; Smith, Sharon; Chou, Patricia S.; Pickering, Roger P.; Huang, Boji; Ruan, June W.; Pulay, Attila J.

2012-01-01

Background Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM- IV currently lacking empirical justification. Methods Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. Results Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. Conclusion Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria

Novel psychoactive substances: the pharmacology of stimulants and hallucinogens.

PubMed

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

2016-07-01

There are increasing levels of concern relating to the rapidly evolving novel psychoactive substances/NPS and web markets' scenarios. The paper aims at providing an overview of the clinical pharmacological issues related to some of the most popular NPS categories, e.g. stimulants and hallucinogens. NPS intake is typically associated with the imbalance of a complex range of neurotransmitter pathways/receptors, namely: dopamine; cannabinoid/CB1; and 5-HT2A. The intake is almost invariably undetectable with standard screening tests. Hence, it may frequently occur that the acute management of NPS misusers will need to focus on decreasing levels of both self/outward-directed aggression and agitation. Benzodiazepines may be considered as first line treatment. Alternatively, propofol and/or antipsychotics can be administered. Focus will be as well on treatment of possible rhabdomyolysis and hyperthermia. Indeed, future studies should inform better tailored management/treatment strategies.

Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

PubMed Central

Halberstadt, Adam L; Koedood, Liselore; Powell, Susan B; Geyer, Mark A

2012-01-01

Psilocin (4-hydroxy-N,N-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. Psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. In the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-HT) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (HTR) and the behavioral pattern monitor (BPM) in C57BL/6J mice. We also compared the effects of psilocin with those of the putative 5-HT2C receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Psilocin, 1-methylpsilocin, and 5-MeO-DMT induced the HTR, effects that were absent in mice lacking the 5-HT2A receptor gene. When tested in the BPM, psilocin decreased locomotor activity, holepoking, and time spent in the center of the chamber, effects that were blocked by the selective 5-HT1A antagonist WAY-100635 but were not altered by the selective 5-HT2C antagonist SB 242,084 or by 5-HT2A receptor gene deletion. 5-MeO-DMT produced similar effects when tested in the BPM, and the action of 5-MeO-DMT was significantly attenuated by WAY-100635. Psilocin and 5-MeO-DMT also decreased the linearity of locomotor paths, effects that were mediated by 5-HT2C and 5-HT1A receptors, respectively. In contrast to psilocin and 5-MeO-DMT, 1-methylpsilocin (0.6–9.6 mg/kg) was completely inactive in the BPM. These findings confirm that psilocin acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at 5-HT2A sites but is inactive at the 5-HT1A receptor. The fact that 1-methylpsilocin displays greater pharmacological selectivity than psilocin indicates that 1-methylpsilocin represents a potentially useful

Toxicities associated with NBOMe ingestion-a novel class of potent hallucinogens: a review of the literature.

PubMed

Suzuki, Joji; Dekker, Michael A; Valenti, Erin S; Arbelo Cruz, Fabiola A; Correa, Ady M; Poklis, Justin L; Poklis, Alphonse

2015-01-01

A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion. We searched PubMed for relevant English-language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted. A total of 10 citations met the criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analogue identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Of all the patients, 7 (35%) were discharged after a period of observation, whereas 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common abnormalities reported on laboratory tests were elevated level of creatinine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%). NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

The determination of psilocin and psilocybin in hallucinogenic mushrooms by HPLC utilizing a dual reagent acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection system.

PubMed

Anastos, Nicole; Lewis, Simon W; Barnett, Neil W; Sims, D Noel

2006-01-01

This paper describes a procedure for the determination of psilocin and psilocybin in mushroom extracts using high-performance liquid chromatography with postcolumn chemiluminescence detection. A number of extraction methods for psilocin and psilocybin in hallucinogenic mushrooms were investigated, with a simple methanolic extraction being found to be most effective. Psilocin and psilocybin were extracted from a variety of hallucinogenic mushrooms using methanol. The analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was realized through a dual reagent chemiluminescence detection system of acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The chemiluminescence detection system gave improved detectability when compared with UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9) mol/L being obtained for psilocin and psilocybin, respectively. The procedure was applied to the determination of psilocin and psilocybin in three Australian species of hallucinogenic mushroom.

Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features.

PubMed

Lerner, Arturo G; Gelkopf, Marc; Skladman, Irena; Rudinski, Dmitri; Nachshon, Hanna; Bleich, Avi

2003-03-01

An unique and intriguing characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appear during the intoxication, in the absence of recent intake of hallucinogens. Hallucinogen persisting perception disorder (HPPD) is a condition in which the re-experiencing of one or more perceptual symptoms causes significant distress or impairment in social, occupational or other important areas of functioning and may be extremely debilitating. Benzodiazepines are one of the recommended agents for the treatment of HPPD but it is unclear which of them may be more helpful. The goal of our investigation was to assess the efficacy of clonazepam in the treatment of LSD-induced HPPD. Sixteen patients fulfilled entrance criteria. All complained of HPPD with anxiety features for at least 3 months and were drug free at least 3 months. They received clonazepam 2 mg/day for 2 months. Follow-up was continued for 6 months. They were weekly evaluated during the 2 months of clonazepam administration and monthly during the follow-up period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Patients reported a significant relief and the presence of only mild symptomatology during the clonazepam administration. This improvement was clearly sustained and persisted during a 6-month follow-up period. This study suggests that high potency benzodiazepines like clonazepam, which has serotonergic properties, may be more effective than low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD.

When the endogenous hallucinogenic trace amine N,N-dimethyltryptamine meets the sigma-1 receptor.

PubMed

Su, Tsung-Ping; Hayashi, Teruo; Vaupel, D Bruce

2009-03-10

N,N-dimethyltryptamine (DMT) is a hallucinogen found endogenously in human brain that is commonly recognized to target the 5-hydroxytryptamine 2A receptor or the trace amine-associated receptor to exert its psychedelic effect. DMT has been recently shown to bind sigma-1 receptors, which are ligand-regulated molecular chaperones whose function includes inhibiting various voltage-sensitive ion channels. Thus, it is possible that the psychedelic action of DMT might be mediated in part through sigma-1 receptors. Here, we present a hypothetical signaling scheme that might be triggered by the binding of DMT to sigma-1 receptors.

When the Endogenous Hallucinogenic Trace Amine N,N-Dimethyltryptamine Meets the Sigma-1 Receptor

PubMed Central

Su, Tsung-Ping; Hayashi, Teruo; Vaupel, D. Bruce

2011-01-01

N,N-dimethyltryptamine (DMT) is a hallucinogen found endogenously in human brain that is commonly recognized to target the 5-hydroxytryptamine 2A receptor or the trace amine–associated receptor to exert its psychedelic effect. DMT has been recently shown to bind sigma-1 receptors, which are ligand-regulated molecular chaperones whose function includes inhibiting various voltage-sensitive ion channels. Thus, it is possible that the psychedelic action of DMT might be mediated in part through sigma-1 receptors. Here, we present a hypothetical signaling scheme that might be triggered by the binding of DMT to sigma-1 receptors. PMID:19278957

Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.

PubMed

Cozzi, Nicholas V; Gopalakrishnan, Anupama; Anderson, Lyndsey L; Feih, Joel T; Shulgin, Alexander T; Daley, Paul F; Ruoho, Arnold E

2009-12-01

N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N-methyl-N-isopropyltryptamine (MIPT), N,N-dipropyltryptamine (DPT), and N,N-diisopropyltryptamine. We then tested the abilities of these N,N-dialkyltryptamines to inhibit [(3)H]5-HT uptake via the plasma membrane serotonin transporter (SERT) in human platelets and via the vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The tryptamines were also tested as inhibitors of [(3)H]paroxetine binding to the SERT and [(3)H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT, MIPT, DPT, and DIPT inhibit [(3)H]5-HT transport at the SERT with K ( I ) values of 4.00 +/- 0.70, 8.88 +/- 4.7, 0.594 +/- 0.12, and 2.32 +/- 0.46 microM, respectively. At VMAT2, the tryptamines inhibited [(3)H]5-HT transport with K ( I ) values of 93 +/- 6.8, 20 +/- 4.3, 19 +/- 2.3, and 19 +/- 3.1 muM, respectively. On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters.

The Effects of Hallucinogens on Gene Expression.

PubMed

Martin, David A; Nichols, Charles D

2018-01-01

The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.

β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

PubMed Central

Marek, Gerard J.; Ramos, Brian P.

2018-01-01

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears

LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

PubMed

Barker, Steven A; Borjigin, Jimo; Lomnicka, Izabela; Strassman, Rick

2013-12-01

We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat. Copyright © 2013 John Wiley & Sons, Ltd.

Two Cases of Non-fatal Intoxication with a Novel Street Hallucinogen: 3-Methoxy-Phencyclidine.

PubMed

Zidkova, Monika; Hlozek, Tomas; Balik, Martin; Kopecky, Ondrej; Tesinsky, Pavel; Svanda, Jan; Balikova, Marie Anna

2017-05-01

3-Methoxy-phencyclidine (3-MeO-PCP) is a structural derivative of the dissociative hallucinogen phencyclidine (PCP). Although PCP toxicity is well documented, little is known about this new psychoactive substance despite being available on the black market even in central Europe. The objective of this case report is to present clinical and laboratory data of analytically confirmed non-fatal intoxication of two subjects with 3-MeO-PCP. A preliminary assessment of potential metabolites excreted into urine was enabled using the liquid chromatography high resolution mass spectrometric method. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

PubMed

Halberstadt, Adam L

2016-04-01

Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by

Behavioral and Pharmacokinetic Interactions Between Monoamine Oxidase Inhibitors and the Hallucinogen 5-Methoxy-N,N-dimethyltryptamine

PubMed Central

Halberstadt, Adam L.

2016-01-01

Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography–electrospray ionization–selective reaction monitoring–tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions.

PubMed

Beck, O; Helander, A; Karlson-Stiber, C; Stephansson, N

1998-01-01

The use of mushrooms containing the hallucinogenic substance psilocybin for intentional intoxication is relatively common. Occasionally, this results in adverse reactions with typical tachycardia that is not evidently caused by psilocybin. This study demonstrates the presence of phenylethylamine in the species Psilocybe semilanceata using gas chromatography-mass spectrometry and shows that the amount of this substance may vary much more than that of psilocybin. The highest amount of phenylethylamine (146 microg/g wet weight) was observed in mushrooms from a case of three young men hospitalized because of adverse reactions. Comparison of the symptoms observed in clinical cases of magic mushroom intoxication with those after intake of pure psilocybin or phenylethylamine suggests that phenylethylamine might have a role in the development of adverse reactions to Psilocybe mushroom intake.

An intravenous self-administration procedure for assessing the reinforcing effects of hallucinogens in nonhuman primates.

PubMed

Goodwin, Amy K

Self-administration procedures are the gold standard for investigating the reinforcing effects of drugs. The notable exception to good correspondence between laboratory self-administration studies and human drug taking behavior has historically been the classic hallucinogens. The present study used a well-established daily access procedure, followed by a novel intermittent access procedure, to investigate the reinforcing effects of LSD in baboons. Rates of self-injection in the daily access procedure were minimal. One baboon self-administered 0.001mg/kg and a second baboon self-administered 0.0032mg/kg above vehicle levels, though rates of self-injection were clearly low and neither of the two remaining baboons self-administered any LSD dose tested in the daily access procedure. Rates of self-injection using an intermittent access procedure with discriminative stimuli resulted in two doses of LSD being self-administered above vehicle levels in two of three baboons tested (0.01 and 0.032mg/kg in one baboon; 0.0032 and 0.01mg/kg in a second). In addition, the number of self-injections at these doses was higher (range=3-6 injections) in the intermittent access procedure than in the daily access procedure (range=1-2 injections). The present study is the first to demonstrate LSD self-administration in a laboratory animal, and though the results are limited, they indicate intermittent access procedures with discriminative stimuli may provide a reliable and valid method for investigating the reinforcing effects of IV self-administered hallucinogens in laboratory animals. The usefulness of such procedures should be further evaluated in a larger number of subjects. Copyright © 2016. Published by Elsevier Inc.

Hallucinogenic drugs and plants in psychotherapy and shamanism.

PubMed

Metzner, R

1998-01-01

Western psychotherapy and indigenous shamanic healing systems have both used psychoactive drugs or plants for healing and obtaining knowledge (called "diagnosis" or "divination" respectively). While there are superficial similarities between psychedelic-assisted psychotherapy and shamanic healing with hallucinogenic plants, there are profound differences in the underlying worldview and conceptions of reality. Four paradigms are reviewed: (1) psychedelic psychotherapy within the standard Western paradigm--here the drug is used to amplify and intensify the processes of internal self-analysis and self-understanding; (2) shamanic rituals of healing and divination, which involve primarily the shaman or healer taking the medicine in order to be able to "see" the causes of illness and know what kind of remedy to apply; (3) syncretic folk religious ceremonies, in which the focus seems to be a kind of community bonding and celebratory worship; and (4) the "hybrid shamanic therapeutic rituals," which incorporate some features of the first two traditions. There are two points in which the worldview of the shamanic and hybrid shamanic ceremonies differs radically from the accepted Western worldview: (1) the belief and assumption (really, perception) that there are multiple realities ("worlds") that can be explored in expanded states of consciousness; and (2) the belief that "spirits," the beings one encounters in dreams and visions, are just as real as the physical organism.

The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.

PubMed

Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R; Cozzi, Nicholas V; Jackson, Meyer B; Ruoho, Arnold E

2009-02-13

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.

The "Endless Trip" among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review.

PubMed

Orsolini, Laura; Papanti, Gabriele Duccio; De Berardis, Domenico; Guirguis, Amira; Corkery, John Martin; Schifano, Fabrizio

2017-01-01

Hallucinogen-persisting perception disorder (HPPD) is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. HPPD was associated with a broader range of LSD (lysergic acid diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (MDMA), psilocybin, mescaline, and psychostimulants. The recent emergence of novel psychoactive substances (NPS) posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. Although HPPD was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). HPPD neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. A critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward HPPD, including the association with some novel substances, are provided here, by means of a literature search on PubMed/Medline, Google Scholar, and Scopus databases without time restrictions, by using a specific set of keywords. Pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.

The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

PubMed Central

Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R.; Cozzi, Nicholas V.; Jackson, Meyer B.; Ruoho, Arnold E.

2010-01-01

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. PMID:19213917

The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research.

PubMed

Langlitz, Nicolas

2010-01-01

The elimination of subjectivity through brain research and the replacement of so-called "folk psychology" by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the "Decade of the Brain," this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs' flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the "psychedelic experience" draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology.

Use, indications and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO.

PubMed

Keup, W

1986-06-01

Information is presented on legal manufacture, distribution, medical uses and in various countries of the stimulants and hallucinogens under consideration by the World Health Organization (WHO). Data are reported from the Substance Abuse Warning System (SAWS) in the F.R.G. and other surveillance systems regarding illicit manufacture, trafficking and abuse of these compounds internationally. In addition, it is pointed out that assessment of the liability of these compounds for abuse must consider not only the substance itself but also its potential metabolic products. These data, collectively, indicate that the substances currently of most concern with respect to abuse are fenetylline and norpseudoephedrine.

Identification of members of the genera Panaeolus and Psilocybe by a DNA test. A preliminary test for hallucinogenic fungi.

PubMed

Lee, J C; Cole, M; Linacre, A

2000-08-14

Abuse of hallucinogens produced by the fungal genera Psilocybe and Panaeolus are a growing problem. Five species from each of the two genera were examined in this preliminary research and a method that will unambiguously identify fungal samples as being of one of these two genera has been developed. The method uses genus specific DNA sequences within the Internal Transcribed Spacer of the ribosomal gene complex. Amplification of a common DNA product and a genus specific product results in two identifiable products, which facilitates the unambiguous identification of material from these two fungi to generic level.

[Poisoning with selected mushrooms with neurotropic and hallucinogenic effect].

PubMed

Marciniak, Beata; Ferenc, Tomasz; Kusowska, Joanna; Ciećwierz, Julita; Kowalczyk, Edward

2010-01-01

Picking mushrooms, especially in summer and autumn, is still very popular in Poland. Despite raising awareness of poisonous mushrooms in the Polish society, year after year hospitals treat many patients diagnosed with poisoning with the most common toxic species of mushroom found in our country. Furthermore, growing interest in hallucinogenic mushrooms among young people has become a serious medical problem of our time. Websites make it incredibly easy for people to obtain information on the morphology and appearance of mushrooms with psychoactive properties, which leads inexperienced pickers to misidentification, resulting frequently in a fatal outcome. The article explores the subject of poisoning with the most common mushrooms with neurotropic effects, these are: Amanita muscaria, Amanita pantherina, Inocybe rubescens, Clitocybe dealbata, Clitocybe rivulosa and Psilocybe semilanceata. Toxins found in these species show symptoms that affect the central nervous system, parasympathetic system as well as the gastro-intestinal system. The effects of poisoning in the mushroom species mentioned above are mild in general, liver and kidney damage occur rarely, but the symptoms depend on both the dosage of the consumed toxins and individual susceptibility. In most cases the treatment is of symptomatic nature. There is no specific treatment. Medical procedures mainly involve induced gastrolavage--stomach pumping (providing that the patient is conscious), prescription of active carbon as well as replacement of lost body fluids and electrolytes. If the muscarinic symptoms prevail it is generally advised to dose atropine. Patients showing the signs of hyperactivity receive tranquilizers or narcoleptics to eliminate psychotic symptoms.

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

PubMed

Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

2014-08-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports.

PubMed

Sanz, Camila; Tagliazucchi, Enzo

2018-01-01

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

Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor.

PubMed

Kayano, Tomohiko; Kitamura, Naoki; Miyazaki, Shunsuke; Ichiyanagi, Tsuyoshi; Shimomura, Norihiro; Shibuya, Izumi; Aimi, Tadanori

2014-04-01

Gymnopilins are substances produced in fruiting bodies of the hallucinogenic mushroom, Gymnopilus junonius. Although, only a few biological effects of gymnopilins on animal tissues have been reported, it is believed that gymnopilins are a key factor of the G. junonius poisoning. In the present study, we found that gymnopilins inhibited ACh-evoked responses in neuronal cell line, PC12 cell, and determine the underlying mechanism. Gymnopilins were purified from wild fruiting bodies of G. junonius collected in Japan. Ca(2+)-imaging revealed that gymnopilins reduced the amplitude of ACh-evoked [Ca(2+)]i rises by about 50% and abolished the ACh responses remaining in the presence of atropine. Gymnopilins greatly reduced the amplitude of [Ca(2+)]i rises evoked by nicotinic ACh receptor agonists, 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP) and nicotine. In the whole-cell voltage clamp recording, gymnopilins inhibited the DMPP-evoked currents, but did not affect the voltage-gated Ca(2+) channel currents. These results indicate that gymnopilins directly act on nicotinic ACh receptors and inhibit their activity. This biological action of gymnopilins may be one of the causes of the G. junonius poisoning. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Japanese hallucinogenic mushrooms Psilocybe and a new synonym of P. subcaerulipes with three asiatic species belong to section Zapotecorum (Higher Basidiomycetes).

PubMed

Guzman, Gaston; Cortes-Perez, Alonso; Ramirez-Guillen, Florencia

2013-01-01

The subtropical Japanese bluing mushroom Psilocybe subcaerulipes, described by Hongo, has several synonyms: P. argentipes by Yokoyama (also from Japan), P. taiwanensis by Guzman and Yang (from Taiwan), and P. thaizapoteca by Guzman, Ramirez-Guillen, and Karunaratna (from Thailand). The study of the holotypes and others specimens of these mushrooms shows that they have basidiospores, pleurocystidia, cheilocystidia, and several other important taxonomic features in common, as well as habitat. Recent discussions of all Japanese hallucinogenic species of Psilocybe and their neurotropic effects are also considered.

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.

PubMed

McKenna, Dennis; Riba, Jordi

2018-01-01

New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain. Using complementary neurophysiological and neuroimaging techniques, we have identified brain areas involved in the cognitive effects induced by this complex botanical preparation. Initial SPECT data showed that ayahuasca modulated activity in higher order association areas of the brain. Increased blood perfusion was observed mainly in anterior brain regions encompassing the frontomedial and anterior cingulate cortices of the frontal lobes, and in the medial regions of the temporal lobes. On the other hand, applying spectral analysis and source location techniques to cortical electrical signals, we found changes in neuronal activity that predominated in more posterior sensory-selective areas of the brain. Now, using functional connectivity analysis of brain oscillations we have been able to reconcile these seemingly contradictory findings. By measuring transfer entropy, a metric based on information theory, we have shown that ayahuasca temporarily modifies the ordinary flow of information within the brain. We propose a model in which ayahuasca reduces top-down constraints and facilitates bottom-up information transfer. By simultaneously enhancing endogenous cortical excitability and reducing higher-order cognitive control, ayahuasca temporarily disrupts neural hierarchies allowing inner exploration and a new outlook on reality.

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

PubMed Central

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

2018-01-01

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

Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-Methylenedioxymethamphetamine (MDMA) and R(−)-MDMA Trained Mice

PubMed Central

Murnane, K. S.; Murai, N.; Howell, L. L.

2009-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse “ecstasy.” The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(−)-enantiomers tend to have hallucinogen-like effects, whereas S(+)-enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(−)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine/norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-hydroxytryptamine (5-HT)2A agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT2A agonist/monoamine reuptake inhibitor N,N-dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA-treated animals but did not substitute for the R(−)-MDMA cue. 2C-T-7 fully substituted in the R(−)-MDMA-trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but whereas cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(−)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further our understanding of the complex nature of the interoceptive effects of MDMA. PMID:19684254

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

PubMed

Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

25C-NBOMe--new potent hallucinogenic substance identified on the drug market.

PubMed

Zuba, Dariusz; Sekuła, Karolina; Buczek, Agnieszka

2013-04-10

This publication reports analytical properties of a new hallucinogenic substance identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine]. The identification was based on results of comprehensive study including several analytical methods, i.e., GC-EI-MS (without derivatization and after derivatization with TFAA), LC-ESI-QTOF-MS, FTIR and NMR. The GC-MS spectrum of 25C-NBOMe was similar to those obtained for other representatives of the 25-NBOMe series, with dominant ions observed at m/z=150, 121 and 91. Fragment ions analogic to those in 2C-C (4-chloro-2,5-dimethoxy-β-phenylethanamine) were also observed, but their intensities were low. Derivatization allowed the determination of molecular mass of the investigated substance. The exact molecular mass and chemical formula were confirmed by LC-QTOF-MS experiments and fragmentation pattern under electrospray ionization was determined. The MS/MS experiments confirmed that the investigated substance was N-(2-methoxy)benzyl derivative of 2C-C. The substance was also characterized by FTIR spectroscopy to corroborate its identity. Final elucidation of the structure was performed by NMR spectroscopy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hallucinogens and dissociative agents naturally growing in the United States.

PubMed

Halpern, John H

2004-05-01

It is usually believed that drugs of abuse are smuggled into the United States or are clandestinely produced for illicit distribution. Less well known is that many hallucinogens and dissociative agents can be obtained from plants and fungi growing wild or in gardens. Some of these botanical sources can be located throughout the United States; others have a more narrow distribution. This article reviews plants containing N,N-dimethyltryptamine, reversible type A monoamine oxidase inhibitors (MAOI), lysergic acid amide, the anticholinergic drugs atropine and scopolamine, or the diterpene salvinorin-A (Salvia divinorum). Also reviewed are mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, and the Amanita muscaria and Amanita pantherina mushrooms that contain muscimol and ibotenic acid. Dangerous misidentification is most common with the mushrooms, but even a novice forager can quickly learn how to properly identify and prepare for ingestion many of these plants. Moreover, through the ever-expanding dissemination of information via the Internet, this knowledge is being obtained and acted upon by more and more individuals. This general overview includes information on the geographical range, drug content, preparation, intoxication, and the special health risks associated with some of these plants. Information is also offered on the unique issue of when bona fide religions use such plants as sacraments in the United States. In addition to the Native American Church's (NAC) longstanding right to peyote, two religions of Brazilian origin, the Santo Daime and the Uniao do Vegetal (UDV), are seeking legal protection in the United States for their use of sacramental dimethyltryptamine-containing "ayahuasca."

Evaluation of the Transport, In Vitro Metabolism and Pharmacokinetics of Salvinorin A, a Potent Hallucinogen

PubMed Central

Teksin, Zeynep S.; Lee, Insong J.; Nemieboka, Noble N.; Othman, Ahmed A.; Upreti, Vijay V.; Hassan, Hazem E.; Syed, Shariq S.; Prisinzano, Thomas E.; Eddington, Natalie D.

2009-01-01

Salvinorin A is an unregulated potent hallucinogen isolated from the leaves of Salvia divinorum. It is the only known non-nitrogenous kappa-opioid selective agonist and rivals synthetic lysergic acid diethylamide (LSD) in potency. This objective of this study was to characterize the in vitro transport, in vitro metabolism, and pharmacokinetic properties of Salvinorin A. The transport characteristics of Salvinorin A were assessed using MDCK-MDR1 cell monolayers. The P-glycoprotein (P-gp) affinity status was assessed by the P-gp ATPase assay. In vitro metabolism studies were performed with various specific human CYP450 isoforms and UGT2B7 to assess the metabolic characteristics of Salvinorin A. Cohorts (n=3) of male Sprague Dawley rats were used to evaluate the pharmacokinetics and brain distribution of Salvinorin A (10 mg/kg, intraperitonal (i.p.) over a 240 min period. A validated UV-HPLC and LC/MS/MS method was used to quantify the hallucinogen concentrations obtained from the in vitro and in vivo studies, respectively. Salvinorin A displayed a high secretory transport in the MDCK-MDR1 cells (4.07±1.34 × 10-5 cm/s). Salvinorin A also stimulated the P-gp ATPase activity in a concentration (5-10 μm) dependent manner, suggesting that it may be a substrate of P-gp. A significant decrease in Salvinorin A concentration ranging from 14.7±0.80 % to 31.1±1.20 % was observed after incubation with CYP2D6, CYP1A1, CYP2C18, and CYP2E1, respectively. A significant decrease was also observed after incubation with UGT2B7. These results suggest that Salvinorin A may be a substrate of UGT2B7, CYP2D6, CYP1A1, CYP2E1 and CYP2C18. The in vivo pharmacokinetic study showed a relatively fast elimination with a half-life (t1/2) of 75 min and a clearance (Cl/F) of 26 L/h/kg. The distribution was extensive (Vd of 47.1 L/kg), however the brain to plasma ratio was 0.050. Accordingly, the brain half life was relatively short, 36 min. Salvinorin A is rapidly eliminated after i.p. dosing

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability.

PubMed

Carhart-Harris, Robin L; Williams, Tim M; Sessa, Ben; Tyacke, Robin J; Rich, Ann S; Feilding, Amanda; Nutt, David J

2011-11-01

This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research.

PubMed

Cachat, Jonathan; Kyzar, Evan J; Collins, Christopher; Gaikwad, Siddharth; Green, Jeremy; Roth, Andrew; El-Ounsi, Mohamed; Davis, Ari; Pham, Mimi; Landsman, Samuel; Stewart, Adam Michael; Kalueff, Allan V

2013-01-01

An indole alkaloid, ibogaine is the principal psychoactive component of the iboga plant, used by indigenous peoples in West Africa for centuries. Modulating multiple neurotransmitter systems, the drug is a potent hallucinogen in humans, although its psychotropic effects remain poorly understood. Expanding the range of model species is an important strategy for translational neuroscience research. Here we exposed adult zebrafish (Danio rerio) to 10 and 20mg/L of ibogaine, testing them in the novel tank, light-dark box, open field, mirror stimulation, social preference and shoaling tests. In the novel tank test, the zebrafish natural diving response (geotaxis) was reversed by ibogaine, inducing initial top swimming followed by bottom dwelling. Ibogaine also attenuated the innate preference for dark environments (scototaxis) in the light-dark box test. While it did not exert overt locomotor or thigmotaxic responses in the open field test, the drug altered spatiotemporal exploration of novel environment, inducing clear preference of some areas over others. Ibogaine also promoted 'mirror' exploration in the mirror stimulation test, disrupted group cohesion in the shoaling test, and evoked strong coloration responses due to melanophore aggregation, but did not alter brain c-fos expression or whole-body cortisol levels. Overall, our results support the complex pharmacological profile of ibogaine and its high sensitivity in zebrafish models, dose-dependently affecting multiple behavioral domains. While future investigations in zebrafish may help elucidate the mechanisms underlying these unique behavioral effects, our study strongly supports the developing utility of aquatic models in hallucinogenic drug research. High sensitivity of three-dimensional phenotyping approaches applied here to behavioral effects of ibogaine in zebrafish provides further evidence of how 3D reconstructions of zebrafish swimming paths may be useful for high-throughput pharmacological screening

NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review.

PubMed

Kyriakou, C; Marinelli, E; Frati, P; Santurro, A; Afxentiou, M; Zaami, S; Busardo, F P

2015-09-01

NBOMe is a class of emerging new psychoactive substances that has recently gained prominence in the drug abuse market. NBOMes are N-2-methoxy-benzyl substituted 2C class of hallucinogens, currently being marked online as "research chemicals" under various names: N-bomb, Smiles, Solaris, and Cimbi. This article reviews available literature on the pharmacology; the analytical methods currently used for the detection and quantification of NBOMe in biological matrices and blotters, together with intoxication cases and NBOMe-related fatalities. Relevant scientific articles were identified from Medline, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar, through June 2015 using the following keywords: "NBOMe", "Nbomb", "Smiles", "intoxication", "toxicity" "fatalities", "death", "pharmacology", "5-HT2A receptor", "analysis" and "analytical methods". The main key word "NBOMe" was individually searched in association to each of the others. The review of the literature allowed us to identify 43 citations on pharmacology, analytical methods and NBOMe-related toxicities and fatalities. The high potency of NBOMes (potent agonists of 5-HT2A receptor) has led to several severe intoxications, overdose and traumatic fatalities; thus, their increase raises significant public health concerns. Moreover, due to the high potency and ease of synthesis, it is likely that their recreational use will become more widespread in the future. The publication of new data, case reports and evaluation of the NBOMes metabolites is necessary in order to improve knowledge and awareness within the forensic community.

Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

PubMed

Kärkkäinen, J; Forsström, T; Tornaeus, J; Wähälä, K; Kiuru, P; Honkanen, A; Stenman, U H; Turpeinen, U; Hesso, A

2005-01-01

Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues.

The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT(1A) and 5-HT(2A) receptors.

PubMed

Riga, Maurizio S; Bortolozzi, Analia; Campa, Letizia; Artigas, Francesc; Celada, Pau

2016-02-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT(1A)/5-HT(2A)-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT(1A)-R and 5-HT(2A)-R, using wild type (WT) and 5-HT(2A)-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT(1A)-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT(1A)-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT(1A)-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT(1A)-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT(2A)-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hunting and hallucinogens: The use psychoactive and other plants to improve the hunting ability of dogs.

PubMed

Bennett, Bradley C; Alarcón, Rocío

2015-08-02

Cultures throughout the world give plants to their dogs in order to improve hunting success. These practices are best developed in lowland Ecuador and Peru. There is no experimental evidence for the efficacy of these practices nor critical reviews that consider possible pharmacological effects on dogs based on the chemistry of the ethnoverterinary plants. This review has three specific aims: (1) determine what plants the Ecuadorian Shuar and Quichua give to dogs to improve their hunting abilities, (2) determine what plants other cultures give to dogs for the same purpose, and (3) assess the possible pharmacological basis for the use of these plants, particularly the psychoactive ones. We gathered Shuar (Province of Morona-Santiago) and Quichua (Napo and Orellano Provinces) data from our previous publications and field notes. All specimens were vouchered and deposited in QCNE with duplicates sent to NY and MO. Data presented from other cultures derived from published studies on ethnoveterinary medicine. Species names were updated, when necessary, and family assignments follow APG III (Angiosperm Phylogeny Group, 2009. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG III. Bot. J. Linn. Soc. 161, 105-121). Chemical data were found using PubMed and SciFinder. The Shuar and Quichua of Ecuador use at least 22 species for ethnoveterinary purposes, including all but one of their principal hallucinogens. Literature surveys identified 43 species used in other cultures to improve hunting ability. No published studies have examined the pharmacological active of these plant species in dogs. We, thus, combined phytochemical data with the ethnobotanical reports of each plant and then classified each species into a likely pharmacological category: depuratives/deodorant, olfactory sensitizer, ophthalmic, or psychoactive. The use of psychoactive substances to improve a dog׳s hunting ability seems counterintuitive, yet

Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice

PubMed Central

Gray, Bradley W.; Bailey, Jessica M.; Smith, Douglas; Hansen, Martin; Kristensen, Jesper L.

2014-01-01

Rationale 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized. Objective 25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(−)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination. Methods Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization. Results 25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55%) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. Conclusions 25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo. PMID:25224567

The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

PubMed Central

Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

2014-01-01

Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

PubMed

Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

2015-01-01

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Practical aspects of genetic identification of hallucinogenic and other poisonous mushrooms for clinical and forensic purposes

PubMed Central

Kowalczyk, Marek; Sekuła, Andrzej; Mleczko, Piotr; Olszowy, Zofia; Kujawa, Anna; Zubek, Szymon; Kupiec, Tomasz

2015-01-01

Aim To assess the usefulness of a DNA-based method for identifying mushroom species for application in forensic laboratory practice. Methods Two hundred twenty-one samples of clinical forensic material (dried mushrooms, food remains, stomach contents, feces, etc) were analyzed. ITS2 region of nuclear ribosomal DNA (nrDNA) was sequenced and the sequences were compared with reference sequences collected from the National Center for Biotechnology Information gene bank (GenBank). Sporological identification of mushrooms was also performed for 57 samples of clinical material. Results Of 221 samples, positive sequencing results were obtained for 152 (69%). The highest percentage of positive results was obtained for samples of dried mushrooms (96%) and food remains (91%). Comparison with GenBank sequences enabled identification of all samples at least at the genus level. Most samples (90%) were identified at the level of species or a group of closely related species. Sporological and molecular identification were consistent at the level of species or genus for 30% of analyzed samples. Conclusion Molecular analysis identified a larger number of species than sporological method. It proved to be suitable for analysis of evidential material (dried hallucinogenic mushrooms) in forensic genetic laboratories as well as to complement classical methods in the analysis of clinical material. PMID:25727040

Practical aspects of genetic identification of hallucinogenic and other poisonous mushrooms for clinical and forensic purposes.

PubMed

Kowalczyk, Marek; Sekuła, Andrzej; Mleczko, Piotr; Olszowy, Zofia; Kujawa, Anna; Zubek, Szymon; Kupiec, Tomasz

2015-02-01

To assess the usefulness of a DNA-based method for identifying mushroom species for application in forensic laboratory practice. Two hundred twenty-one samples of clinical forensic material (dried mushrooms, food remains, stomach contents, feces, etc) were analyzed. ITS2 region of nuclear ribosomal DNA (nrDNA) was sequenced and the sequen-ces were compared with reference sequences collected from the National Center for Biotechnology Information gene bank (GenBank). Sporological identification of mushrooms was also performed for 57 samples of clinical material. Of 221 samples, positive sequencing results were obtained for 152 (69%). The highest percentage of positive results was obtained for samples of dried mushrooms (96%) and food remains (91%). Comparison with GenBank sequences enabled identification of all samples at least at the genus level. Most samples (90%) were identified at the level of species or a group of closely related species. Sporological and molecular identification were consistent at the level of species or genus for 30% of analyzed samples. Molecular analysis identified a larger number of species than sporological method. It proved to be suitable for analysis of evidential material (dried hallucinogenic mushrooms) in forensic genetic laboratories as well as to complement classical methods in the analysis of clinical material.

A novel hemagglutinin with antiproliferative activity against tumor cells from the hallucinogenic mushroom Boletus speciosus.

PubMed

Sun, Jian; Ng, Tzi-Bun; Wang, Hexiang; Zhang, Guoqing

2014-01-01

Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin) was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg(2+) and slightly inhibited by Fe(2+), Ca(2+), and Pb(2+). None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210) in vitro, with IC50 of 4.7 μ M and 7.0 μ M, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μ M.

The hallucinogenic diterpene salvinorin A inhibits leukotriene synthesis in experimental models of inflammation.

PubMed

Rossi, Antonietta; Pace, Simona; Tedesco, Federica; Pagano, Ester; Guerra, Germano; Troisi, Fabiana; Werner, Markus; Roviezzo, Fiorentina; Zjawiony, Jordan K; Werz, Oliver; Izzo, Angelo A; Capasso, Raffaele

2016-04-01

Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Novel Hemagglutinin with Antiproliferative Activity against Tumor Cells from the Hallucinogenic Mushroom Boletus speciosus

PubMed Central

Ng, Tzi-Bun; Wang, Hexiang; Zhang, Guoqing

2014-01-01

Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin) was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg2+ and slightly inhibited by Fe2+, Ca2+, and Pb2+. None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210) in vitro, with IC50 of 4.7 μM and 7.0 μM, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μM. PMID:24977148

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.

Gymnopilin--a substance produced by the hallucinogenic mushroom, Gymnopilus junonius--mobilizes intracellular Ca(2+) in dorsal root ganglion cells.

PubMed

Miyazaki, Shunsuke; Kitamura, Naoki; Nishio, Aiko; Tanaka, Saki; Kayano, Tomohiko; Moriya, Taiki; Ichiyanagi, Tsuyoshi; Shimomura, Norihiro; Shibuya, Izumi; Aimi, Tadanori

2012-04-01

Gymnopilus junonius is a widely spread mushroom in Japan and well known as a hallucinogenic mushroom. Gymnopilin was purified from the fruiting body of G. junonius and was reported to act on the spinal cord and depolarize motoneurons. This is the only evidence that gymnopilin has a biological effect on animals and no mechanism of the action has been determined at all. In this study, we examined effects of gymnopilin on intracellular Ca(2+) concentrations ([Ca(2+)](i)) of cultured cells isolated from the dorsal root ganglion (DRG) of the rat. The cell culture consisted of neurons and non-neuronal cells. Gymnopilin increased [Ca(2+)](i) in both the types of cells. The gymnopilinevoked [Ca(2+)](i) rise in the non-neuronal cells was inhibited by cyclopiazonic acid and U-73122, inhibitors of Ca(2+)-ATPase of the intracellular Ca(2+) store and phospholipase C, respectively, but not by removal of extracellular Ca(2+). These results indicate that gymnopilin activated phospholipase C and mobilize Ca(2+) from the intracellular Ca(2+) store in non-neuronal cells from the DRG. This is the first report to show that gymnopilin directly acts on cells isolated from the mammalian nervous system.

The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain.

PubMed

Frankel, Paul S; Cunningham, Kathryn A

2002-12-27

The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (P<0.05) in the number of c-Fos-positive cells detected in the anterior cingulate cortex at 1 h, the shell of the nucleus accumbens at 1 and 2 h, the bed nucleus of stria terminalis lateral at 2 h and the paraventricular hypothalamic nucleus at 1, 2 and 4 h following systemic d-LSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD. Copyright 2002 Elsevier Science B.V.

Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

PubMed Central

Spain, Aisling; Howarth, Clare; Khrapitchev, Alexandre A.; Sharp, Trevor; Sibson, Nicola R.; Martin, Chris

2015-01-01

The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N = 6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data. PMID:26192543

The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors.

PubMed

Riga, Maurizio S; Lladó-Pelfort, Laia; Artigas, Francesc; Celada, Pau

2017-12-06

5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT 1A /5-HT 2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT 1A and 5-HT 2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT 2A -R knockout (KO2A) mice. We performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. We also examined the prevention of 5-MeO-DMT effects by the 5-HT 1A -R antagonist WAY-100635. 5-MeO-DMT affected oscillatory activity more in cortical than in thalamic areas. More marked effects were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5-MeO-DMT effects on oscillatory activity. The present results indicate that hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration of prefrontal and visual activities. The prevention of these effects by WAY-100635 in KO2A mice supports the potential usefulness of 5-HT 1A receptor antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta activity and cortico-thalamic coherence may be related to its antidepressant activity. Copyright © 2017. Published by Elsevier Ltd.

Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway.

PubMed

Ibarra-Lecue, Inés; Mollinedo-Gajate, Irene; Meana, J Javier; Callado, Luis F; Diez-Alarcia, Rebeca; Urigüen, Leyre

2018-04-27

Long-term use of potent cannabis during adolescence increases the risk of developing schizophrenia later in life, but to date, the mechanisms involved remain unknown. Several findings suggest that the functional selectivity of serotonin 2A receptor (5-HT2AR) through inhibitory G-proteins is involved in the molecular mechanisms responsible for psychotic symptoms. Moreover, this receptor is dysregulated in the frontal cortex of schizophrenia patients. In this context, studies involving cannabis exposure and 5-HT2AR are scarce. Here, we tested in mice the effect of an early chronic Δ 9 -tetrahydrocannabinol (THC) exposure on cortical 5-HT2AR expression, as well as on its in vivo and in vitro functionality. Long-term exposure to THC induced a pro-hallucinogenic molecular conformation of the 5-HT2AR and exacerbated schizophrenia-like responses, such as prepulse inhibition disruption. Supersensitive coupling of 5-HT2AR toward inhibitory Gαi1-, Gαi3-, Gαo-, and Gαz-proteins after chronic THC exposure was observed, without changes in the canonical Gαq/11-protein pathway. In addition, we found that inhibition of Akt/mTOR pathway by rapamycin blocks the changes in 5-HT2AR signaling pattern and the supersensitivity to schizophrenia-like effects induced by chronic THC. The present study provides the first evidence of a mechanistic explanation for the relationship between chronic cannabis exposure in early life and increased risk of developing psychosis-like behaviors in adulthood.

DNA-based taxonomic identification of basidiospores in hallucinogenic mushrooms cultivated in "grow-kits" seized by the police: LC-UV quali-quantitative determination of psilocybin and psilocin.

PubMed

Gambaro, Veniero; Roda, Gabriella; Visconti, Giacomo Luca; Arnoldi, Sebastiano; Casagni, Eleonora; Dell'Acqua, Lucia; Farè, Fiorenza; Paladino, Eleonora; Rusconi, Chiara; Arioli, Stefania; Mora, Diego

2016-06-05

The taxonomic identification of the biological material contained in the hallucinogenic mushrooms culture media, was carried out using a DNA-based approach, thus highlighting the usefulness of this approach in the forensic identification of illegal samples also when they are present as basidiospores mixed in culture media and spore-bearing fruiting body are not present. This approach is very useful as it allows the unequivocal identification of potentially illicit material before the cultivation and it enables to stop the material to the Customs and to destroy it due to its dangerousness without cultivating the "grow-kits" and without instructing a criminal case. In fact, even if psilocin and psilocybin and the whole mushrooms are illegal in many countries, there is no specific indication in the law about the so called "grow-kits", containing the spores. To confirm the data obtained by the taxonomic identification, a simple, reliable, efficient LC-UV method, using tryptamine as internal standard, suitable for the forensic quali-quantitative determination of psilocin and psilocybin in hallucinogenic mushroom was optimized, validated and applied to the mushrooms grown after the cultivation of the grow-kits seized by the judicial authority, with the authorization of the Ministry of Health. A cation exchange column was used in a gradient elution mode (Phase A: 50mMK2HPO4; 100mM NaCl pH=3 Phase B: methanol). The developed method was linear over the calibration range with a R(2)>0.9992 for both the analytes. The detection and quantification limits were respectively 0.01 and 0.1μg/mL for psilocybin and 0.05μg/mL and 0.1μg/mL for psilocin and the intra- and inter-day precision was satisfactory (coefficients of variation <2.0% for both the analytes). The content of psilocybin in the mushrooms grown from the seized "grow-kits" ranged from 1.02 to 7.60mg/g of dry vegetable material, while the content of psilocin from 0.415 to 8.36mg/g. Copyright © 2016 Elsevier B.V. All

Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.

PubMed

Barker, S A; Littlefield-Chabaud, M A; David, C

2001-02-10

A method for the solid-phase extraction (SPE) and liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric-isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat brain tissue is reported. Rats were administered DMT or OMB by the intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment. Brains were dissected into discrete areas and analyzed by the methods described as a demonstration of the procedure's applicability. The synthesis and use of two new deuterated internal standards for these purposes are also reported.

Characterization of hallucinogenic phenethylamines using high-resolution mass spectrometry for non-targeted screening purposes.

PubMed

Pasin, Daniel; Cawley, Adam; Bidny, Sergei; Fu, Shanlin

2017-10-01

Hallucinogenic phenethylamines such as 2,5-dimethoxyphenethylamines (2C-X) and their N-(2-methoxybenzyl) derivatives (25X-NBOMe) have seen an increase in novel analogues in recent years. These rapidly changing analogues make it difficult for laboratories to rely on traditional targeted screening methods to detect unknown new psychoactive substances (NPS). In this study, twelve 2C-X, six 2,5-dimethoxyamphetamines (DOX), and fourteen 25X-NBOMe derivatives, including two deuterated derivatives (2C-B-d 6 and 25I-NBOMe-d 9 ), were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Collision-induced dissociation (CID) experiments were performed using collision energies set at 10, 20, and 40 eV. For 2C-X and DOX derivatives, common losses were observed including neutral and radical losses such as NH 3 (17.0265 Da), •CH 6 N (32.0500 Da), C 2 H 7 N (45.0578 Da) and C 2 H 9 N (47.0735 Da). 2C-X derivatives displayed common product ions at m/z 164.0837 ([C 10 H 12 O 2 ] +• ), 149.0603 ([C 9 H 9 O 2 ] + ), and 134.0732 ([C 9 H 10 O] +• ) while DOX derivatives had common product ions at m/z 178.0994 ([C 11 H 14 O 2 ] +• ), 163.0754 ([C 10 H 11 O 2 ] + ), 147.0804 ([C 10 H 11 O] + ), and 135.0810 ([C 9 H 11 O] + ). 25X-NBOMe had characteristic product ions at m/z 121.0654 ([C 8 H 9 O] + ) and 91.0548 ([C 7 H 7 ] + ) with minor common losses corresponding to 2-methylanisole (C 8 H 10 O, 122.0732 Da), 2-methoxybenzylamine (C 8 H 11 NO, 137.0847 Da), and •C 9 H 14 NO (152.1074 Da). Novel analogues of the selected classes can be detected by applying neutral loss filters (NLFs) and extracting the common product ions. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine.

PubMed

Rangel-Barajas, Claudia; Estrada-Sánchez, Ana María; Barton, Scott J; Luedtke, Robert R; Rebec, George V

2017-02-01

The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration. In addition, DOI increased coincident firing between simultaneously recorded neuron pairs within the striatum and between M1 and dorsal striatum. Local field potential (LFP) activity also increased in coherence between M1 and dorsal striatum after DOI in the low frequency gamma band (30-50 Hz), while corticostriatal coherence in delta, theta, alpha, and beta activity decreased. We also assessed corticostriatal LFP activity in relation to the DOI-induced head-twitch response (HTR), a readily identifiable behavior used to assess potential treatments for the conditions it models. The HTR was associated with increased delta and decreased theta power in both M1 and dorsal striatum. Together, our results suggest that DOI dysregulates corticostriatal communication and that the HTR is associated with this dysregulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Performance Liquid Chromatography with Tandem Mass Spectrometry for the Determination of Nine Hallucinogenic 25-NBOMe Designer Drugs in Urine Specimens

PubMed Central

Poklis, Justin L.; Clay, Deborah J.; Poklis, Alphonse

2014-01-01

We present a high-performance liquid chromatography triple quadrupole mass spectrometry (HPLC–MS-MS) method for the identification and quantification of nine serotonin 5-HT2A receptor agonist hallucinogenic substances from a new class of N-methoxybenzyl derivatives of methoxyphenylethylamine (NBOMe) designer drugs in human urine: 25H-NBOMe, 2CC-NBOMe, 25I-NBF, 25D-NBOMe, 25B-NBOMe, 2CT-NBOMe, 25I-NBMD, 25G-NBOMe and 25I-NBOMe. This assay was developed for the Virginia Commonwealth University Clinical and Forensic Toxicology laboratory to screen emergency department specimens in response to an outbreak of N-benzyl-phenethylamine derivative abuse and overdose cases in Virginia. The NBOMe derivatives were rapidly extracted from the urine specimens by use of FASt™ solid-phase extraction columns. Assay performance was determined as recommended for validation by the Scientific Working Group for Forensic Toxicology (SWGTOX) for linearity, lower limit of quantification, lower limit of detection, accuracy/bias, precision, dilution integrity, carryover, selectivity, absolute recovery, ion suppression and stability. Linearity was verified to be from 1 to 100 ng/mL for each of the nine analytes. The bias determined for the NBOMe derivatives was 86–116% with a <14% coefficient of variation over the linear range of the assay. Four different NBOMe derivatives were detected using the presented method in patient urine specimens. PMID:24535338

38 CFR 1.218 - Security and law enforcement at VA facilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by a...

38 CFR 1.218 - Security and law enforcement at VA facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by a...

38 CFR 1.218 - Security and law enforcement at VA facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by a...

38 CFR 1.218 - Security and law enforcement at VA facilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by a...

38 CFR 1.218 - Security and law enforcement at VA facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by a...

44 CFR 15.9 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2012 CFR

2012-10-01

... beverages, narcotic drugs, hallucinogens, marijuana, barbiturates or amphetamines as defined in Title 21 of... property being under the influence of or using or possessing any narcotic drug, marijuana, hallucinogen... influence of alcoholic beverages; (d) Bringing alcoholic beverages, narcotic drugs, hallucinogens, marijuana...

44 CFR 15.9 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2014 CFR

2014-10-01

... beverages, narcotic drugs, hallucinogens, marijuana, barbiturates or amphetamines as defined in Title 21 of... property being under the influence of or using or possessing any narcotic drug, marijuana, hallucinogen... influence of alcoholic beverages; (d) Bringing alcoholic beverages, narcotic drugs, hallucinogens, marijuana...

44 CFR 15.9 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2013 CFR

2013-10-01

... beverages, narcotic drugs, hallucinogens, marijuana, barbiturates or amphetamines as defined in Title 21 of... property being under the influence of or using or possessing any narcotic drug, marijuana, hallucinogen... influence of alcoholic beverages; (d) Bringing alcoholic beverages, narcotic drugs, hallucinogens, marijuana...

44 CFR 15.9 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2011 CFR

2011-10-01

... beverages, narcotic drugs, hallucinogens, marijuana, barbiturates or amphetamines as defined in Title 21 of... property being under the influence of or using or possessing any narcotic drug, marijuana, hallucinogen... influence of alcoholic beverages; (d) Bringing alcoholic beverages, narcotic drugs, hallucinogens, marijuana...

44 CFR 15.9 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2010 CFR

2010-10-01

... beverages, narcotic drugs, hallucinogens, marijuana, barbiturates or amphetamines as defined in Title 21 of... property being under the influence of or using or possessing any narcotic drug, marijuana, hallucinogen... influence of alcoholic beverages; (d) Bringing alcoholic beverages, narcotic drugs, hallucinogens, marijuana...

Mushroom Use by College Students.

ERIC Educational Resources Information Center

Thompson, John P.; And Others

1985-01-01

Surveyed 1,507 college students to investigate the extent of hallucinogenic mushroom use and compared mushroom users to nonusers. Results showed that among the respondents who reported use of hallucinogenic drugs (17 percent), over 85 percent had used hallucinogenic (psilocybin) mushrooms and over half had used mushrooms but no other…

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

PubMed

Strassman, R J; Qualls, C R; Berg, L M

1996-05-01

Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis.

PubMed

Heekeren, K; Neukirch, A; Daumann, J; Stoll, M; Obradovic, M; Kovar, K-A; Geyer, M A; Gouzoulis-Mayfrank, E

2007-05-01

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Code of Federal Regulations, 2012 CFR

2012-01-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic...

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Code of Federal Regulations, 2010 CFR

2010-07-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic...

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Code of Federal Regulations, 2014 CFR

2014-01-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic...

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Code of Federal Regulations, 2013 CFR

2013-07-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic...

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Code of Federal Regulations, 2011 CFR

2011-01-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic...

Human psychopharmacology of N,N-dimethyltryptamine.

PubMed

Strassman, R J

1996-01-01

We generated dose-response data for the endogenous and ultra-short-acting hallucinogen, N,N-dimethyltryptamine (DMT), in a cohort of experienced hallucinogen users, measuring multiple biological and psychological outcome measures. Subjective responses were quantified with a new rating scale, the HRS, which provided better resolution of dose effects than did the biological variables. A tolerance study then was performed, in which volunteers received four closely spaced hallucinogenic doses of DMT. Subjective responses demonstrated no tolerance, while biological measures were inconsistently reduced over the course of the sessions. Thus, DMT remains unique among classic hallucinogens in its inability to induce tolerance to its psychological effects. To assess the role of the 5-HT1A site in mediating DMT's effects, a pindolol pre-treatment study was performed. Pindolol significantly increased psychological responses to DMT, suggesting a buffering effect of 5-HT1A agonism on 5-HT2-mediated psychedelic effects. These data are opposite to those described in lower animal models of hallucinogens' mechanisms of action.

Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial infarction.

PubMed

Borowiak, K S; Ciechanowski, K; Waloszczyk, P

1998-01-01

Intentional intoxication with natural hallucinogenic substances such as hallucinogenic mushrooms continues to be a major problem in the US and Europe, particularly in the harbor complex of northwest Poland (Pomerania). A case is described of Psilocybe intoxication in an 18-year-old man resulting in Wolff-Parkinson-White syndrome, arrhythmia, and myocardial infarction. The indole concentrations of hallucinogenic mushrooms may predict the risk for adverse central nervous system and cardiac toxicity.

Behavioral characterization of 2-O-desmethyl and 5-O-desmethyl metabolites of the phenylethylamine hallucinogen DOM.

PubMed

Eckler, J R; Chang-Fong, J; Rabin, R A; Smith, C; Teitler, M; Glennon, R A; Winter, J C

2003-07-01

The present investigation was undertaken to test the hypothesis that known metabolites of the phenylethylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) are pharmacologically active. This hypothesis was tested by evaluating the ability of racemic DOM metabolites 2-O-desmethyl DOM (2-DM-DOM) and 5-O-desmethyl DOM (5-DM-DOM) to substitute for the stimulus properties of (+)lysergic acid diethylamide (LSD). The data indicate that both metabolites are active in LSD-trained subjects and are significantly inhibited by the selective 5-HT(2A) receptor antagonist M100907. Full generalization of LSD to both 2-DM-DOM and 5-DM-DOM occurred, and 5-DM-DOM was slightly more potent than 2-DM-DOM. Similarly, 5-DM-DOM had a slightly higher affinity than 2-DM-DOM for both 5-HT(2A) and 5-HT(2C) receptors. Additionally, it was of interest to determine if the formation of active metabolite(s) resulted in a temporal delay associated with maximal stimulus effects of DOM. We postulated that if metabolite formation resulted in the aforementioned delay, direct administration of the metabolites might result in maximally stable stimulus effects at an earlier pretreatment time. This hypothesis was tested by evaluating (1) the time point at which DOM produces the greatest degree of LSD-appropriate responding, (2) the involvement of 5-HT(2A) receptor in the stimulus effects of DOM at various pretreatment times by administration of M100907 and (3) the ability of 2-DM-DOM and 5-DM-DOM to substitute for the stimulus properties of LSD using either 15- or 75-min pretreatment time. The data indicate that (a) the DOM stimulus produces the greatest degree of LSD-appropriate responding at the 75-min time point in comparison with earlier pretreatment times and (b) the stimulus effects of DOM are differentially antagonized by M100907 and this effect is a function of DOM pretreatment time prior to testing. Both 2-DM-DOM and 5-DM-DOM were found to be most active, at all doses tested

32 CFR 228.9 - Prohibition on narcotics and illegal substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply in...

32 CFR 228.9 - Prohibition on narcotics and illegal substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply in...

32 CFR 228.9 - Prohibition on narcotics and illegal substances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply in...

32 CFR 228.9 - Prohibition on narcotics and illegal substances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply in...

32 CFR 228.9 - Prohibition on narcotics and illegal substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply in...

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

PubMed

De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.

PubMed

Strassman, R J; Qualls, C R

1994-02-01

To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.

PubMed

van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally; Risbrough, Victoria B; Halberstadt, Adam L

2011-01-01

Serotonin-1A (5-HT(1A)) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT(1A) receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT(1A) receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modeling NMDA receptor hypoactivity, was unchanged in the knockouts. The effect of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) was markedly reduced in 5-HT(1A) receptor knockout mice. There were no changes in apomorphine-induced disruption of PPI, a model of sensory gating deficits seen in schizophrenia. Similarly, there were no major changes in density of dopamine transporters (DAT) or dopamine D(1) or D(2) receptors which could explain the behavioural changes observed in 5-HT(1A) receptor knockout mice. These results extend our insight into the possible role of these receptors in aspects of schizophrenia. As also suggested by previous studies using agonist and antagonist drugs, 5-HT(1A) receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ergot and Its Alkaloids

PubMed Central

Schiff, Paul L.

2006-01-01

This manuscript reviews the history and pharmacognosy of ergot, and describes the isolation/preparation, chemistry, pharmacodynamics, and pharmacotherapeutics of the major ergot alkaloids and their derivatives. A brief discussion of the hallucinogenic properties of lysergic acid diethylamide is also featured. An abbreviated form of the material found in this paper is presented in a 4-hour didactic format to third-professional year PharmD students as part of their study of vascular migraine headaches, Parkinson's disease, and naturally occurring hallucinogens/hallucinogen derivatives in the modular course offering Neurology/Psychiatry. PMID:17149427

Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

PubMed Central

Fantegrossi, William E.; Reissig, Chad J.; Katz, Elyse B.; Yarosh, Haley L.; Rice, Kenner C.; Winter, Jerrold C.

2008-01-01

N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin), or 3,4-methylenedioxymethamphetamine (MDMA). A separate group of rats was also trained to recognize DPT itself as a discriminative stimulus, and in all cases, the behavioral effects of DPT were challenged with the selective serotonin (5-HT)2A antagonist M100907, the 5-HT1A selective antagonist WAY-100635, or their combination. In the head twitch assay, DPT elicited dose-dependent effects, producing a biphasic dose-effect curve. WAY-100635 produced a parallel rightward shift in the dose-effect curve for head twitches, indicative of surmountable antagonism, but the antagonist effects of M100907 were functionally insurmountable. DPT produced partial to full substitution when tested in rats trained to discriminate LSD, psilocybin or MDMA, and served as a discriminative stimulus. In all cases, the antagonist effects of M100907 were more profound than were those of WAY-100635. DPT is thus active in two rodent models relevant to 5-HT2 agonist activity. The effectiveness with which M100907 antagonizes the behavioral actions of this compound strongly suggests that the 5-HT2A receptor is an important site of action for DPT, but the modulatory actions of WAY-100635 also imply a 5-HT1A-mediated component to the actions of this compound. PMID:17905422

Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.

PubMed

Muschamp, John W; Regina, Meredith J; Hull, Elaine M; Winter, Jerrold C; Rabin, Richard A

2004-10-08

The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine.

PubMed

Blair, J B; Marona-Lewicka, D; Kanthasamy, A; Lucaites, V L; Nelson, D L; Nichols, D E

1999-03-25

The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b substituted for LSD or DOI up to doses of 50 micromol/kg. By comparison, 1a fully substituted in LSD-trained rats. However, 3a and 3b fully substituted for the 5-HT1A agonist LY293284 ((-)-(4R)-6-acetyl-4-(di-n-propylamino)-1,3,4, 5-tetrahydrobenz[c,d]indole). Both 3a and 3b induced a brief "serotonin syndrome" and salivation, an indication of 5-HT1A receptor activation. At the cloned human 5-HT2A receptor 3b had about twice the affinity of 3a. At the cloned human 5-HT2B and 5-HT2C receptors, however, 3a had about twice the affinity of 3b. Therefore, thiophene lacks equivalence as a replacement for the phenyl ring in the indole nucleus of tryptamines that bind to 5-HT2 receptor subtypes and possess LSD-like behavioral effects. Whereas both of the thienopyrroles had lower affinity than the corresponding 1a at 5-HT2 receptors, 3a and 3b had significantly greater affinity than 1a at the 5-HT1A receptor. Thus, thienopyrrole does appear to serve as a potent bioisostere for the indole nucleus in compounds that bind to the serotonin 5-HT1A receptor. These differences in biological activity suggest that serotonin receptor isoforms are very sensitive to subtle changes in the electronic character of the aromatic systems of indole compounds.

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms.

PubMed

Barrett, Frederick S; Bradstreet, Matthew P; Leoutsakos, Jeannie-Marie S; Johnson, Matthew W; Griffiths, Roland R

2016-12-01

Acute adverse psychological reactions to classic hallucinogens ("bad trips" or "challenging experiences"), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens. © The Author(s) 2016.

Is Shame Hallucinogenic?

PubMed Central

McCarthy-Jones, Simon

2017-01-01

Research into the causes of “hearing voices,” formally termed auditory verbal hallucinations (AVH), has primarily focused on cognitive mechanisms. A potentially causative role for emotion has been relatively neglected. This paper uses historical and contemporary case studies of AVH to tentatively generate the hypothesis that shame can be a causal factor in the onset of AVH. Other sources of support for the generation of this hypothesis are then sought. First, evidence is examined for a role of shame in the etiology of post-traumatic stress disorder, a condition that is characterized by phenomena related to AVH (intrusions and dissociation) and in which a substantial minority of sufferers report AVH. Second, the effect on AVH of a psychological therapy specifically designed to counteract shame (Compassion Focused Therapy) is noted. The hypothesis generation process is then expanded to propose mechanisms that could mediate a relation between shame and AVH. It is proposed that employing absorbed or avoidant strategies to deal with shame may lead to AVH through mediating mechanisms such as rumination, suppression, and dissociation. Evolutionary reasons for a relation between shame and AVH are also proposed, including that AVH may be an evolved mechanism to encourage self-protective behaviors in the wake of trauma. It is concluded that existing research supports the generation of this paper's hypothesis, which is now worthy of dedicated empirical testing. PMID:28824494

Parental, Personality, and Peer Correlates of Psychoactive Mushroom Use.

ERIC Educational Resources Information Center

Anglin, M. Douglas; And Others

1986-01-01

College undergraduates (N=53) reporting use of a hallucinogenic mushroom (Psilocybe) were matched to nonusers. Hallucinogenic mushroom use by men was most associated with peers' mushroom use, whereas mushroom use by women was most associated with parental drug use, especially fathers' marijuana use. Personality measures were secondary in…

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

PubMed Central

Barrett, Frederick S.; Bradstreet, Matthew P.; Leoutsakos, Jeannie-Marie S.; Johnson, Matthew W.; Griffiths, Roland R.

2017-01-01

Acute adverse psychological reactions to classic hallucinogens (“bad trips”, or “challenging experiences”), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the 5-Dimensional Altered States of Consciousness questionnaire) in an internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire (CEQ). The stand-alone CEQ was then validated in a separate sample. Seven CEQ factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with the difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The CEQ provides a basis for future investigation of predictors and outcomes of challenging experiences with psilocybin, and should be explored as a measure of challenging experiences with the broad class of classic hallucinogens. PMID:27856683

Hyphenated GC-FTIR and GC-MS techniques applied in the analysis of bioactive compounds

NASA Astrophysics Data System (ADS)

Gosav, Steluta; Paduraru, Nicoleta; Praisler, Mirela

2014-08-01

The drugs of abuse, which affect human nature and cause numerous crimes, have become a serious problem throughout the world. There are hundreds of amphetamine analogues on the black market. They consist of various alterations of the basic amphetamine molecular structure, which are yet not yet included in the lists of forbidden compounds although they retain or slightly modify the hallucinogenic effects of their parent compound. It is their important variety that makes their identification quite a challenge. A number of analytical procedures for the identification of amphetamines and their analogues have recently been reported. We are presenting the profile of the main hallucinogenic amphetamines obtained with the hyphenated techniques that are recommended for the identification of illicit amphetamines, i. e. gas chromatography combined with mass spectrometry (GC-MS) and gas chromatography coupled with Fourier transform infrared spectrometry (GC-FTIR). The infrared spectra of the analyzed hallucinogenic amphetamines present some absorption bands (1490 cm-1, 1440 cm-1, 1245 cm-1, 1050 cm-1 and 940 cm-1) that are very stable as position and shape, while their intensity depends of the side-chain substitution. The specific ionic fragment of the studied hallucinogenic compounds is the 3,4-methylenedioxybenzyl cation (m/e = 135) which has a small relative abundance (lesser than 20%). The complementarity of the above mentioned techniques for the identification of hallucinogenic compounds is discussed.

Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

PubMed

Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

2013-01-23

The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

Occurrence of psilocybin and psilocin in Psilocybe pseudobullacea (Petch) Pegler from the Venezuelan Andes.

PubMed

Marcano, V; Morales Méndez, A; Castellano, F; Salazar, F J; Martinez, L

1994-07-08

Using thin-layer chromatographic and spectroscopic (UV) methods two Psilocybe species from the Venezuelan Andes were analysed for the hallucinogens psilocybin and psilocin. These species are: P. montana (Pers. ex Fr.) Kumm and P. pseudobullacea (Petch) Pegler. Both hallucinogens were found in P. pseudobullacea, while P. montana was found to be exempt of these compounds.

Adverse consequences of lysergic acid diethylamide.

PubMed

Abraham, H D; Aldridge, A M

1993-10-01

The continued endemic use of hallucinogenic drugs, and of LSD in particular, raises concern regarding their short and long term adverse consequences. The epidemiology of LSD abuse is reviewed suggesting an increase in LSD use among the young as the prevalence rates for other substances continues to fall. Evidence supports the association of LSD use with panic reactions, prolonged schizoaffective psychoses and post-hallucinogen perceptual disorder, the latter being present continually for as long as 5 years. Evidence does not support claims of genetic disorders arising from hallucinogens. In light of the foregoing, current data confirm earlier findings of long lasting psychopathology arising in vulnerable individuals from the use of LSD. A hypothetical long term molecular mechanism of adverse effects is proposed.

JPRS Report, Science & Technology, USSR: Life Sciences.

DTIC Science & Technology

1987-08-12

between the structure and effect of hallucinogens is beyond the scope of this article. It should be noted though that in the phenylethylamine series...The majority of derivatives of alpha-methyl- phenylethylamine (amphetamine) surpass mescaline with respect to their hallucinogenic effect . Thus...Metlitskiy (deceased), Yu. T. Dyakov, et al. ZHURNAL OBSHCHEY BIOLOGII, No 6, Nov-Dec 86) Effect of Dehydration and Heating on Bioelectrical

LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex.

PubMed

Arvanov, V L; Liang, X; Russo, A; Wang, R Y

1999-09-01

Both the phenethylamine hallucinogen (-)-1-2, 5-dimethoxy-4-bromophenyl-2-aminopropane (DOB), a selective serotonin 5-HT2A,2C receptor agonist, and the indoleamine hallucinogen D-lysergic acid diethylamide (LSD, which binds to 5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and alpha1 and alpha2 adrenergic receptors), but not their non-hallucinogenic congeners, inhibited N-methyl-D-aspartate (NMDA)-induced inward current and NMDA receptor-mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5-HT in the presence of selective 5-HT1A and 5-HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5-HT on the NMDA transmission was blocked by the 5-HT2A receptor antagonists R-(+)-alpha-(2, 3-dimethoxyphenil)-1-[4-fluorophenylethyl]-4-piperidineme thanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5-HT, suggesting a partial agonist action. Whereas N-(4-aminobutyl)-5-chloro-2-naphthalenesulphonamide (W-7, a calmodulin antagonist) and N-[2-[[[3-(4'-chlorophenyl)- 2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxy-b enzenesulphonamide phosphate (KN-93, a Ca2+/CaM-KII inhibitor), but not the negative control 2-[N-4'methoxybenzenesulphonyl]amino-N-(4'-chlorophenyl)-2-propeny l-N -methylbenzylamine phosphate (KN-92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5-HT2A receptors via a Ca2+/CaM-KII-dependent signal transduction pathway as partial agonists and modulating the NMDA receptors-mediated sensory, perceptual, affective and cognitive processes.

[Concentration of selected microelements in blood serum of rats exposed to the action of psilocin and phenylethylamine].

PubMed

Majdanik, Sławomir; Borowiak, Krzysztof; Brzezńska, Maria; Machoy-Mokrzyńska, Anna

2007-01-01

Natural hallucinogens (including Psilocybe mushrooms) became popular in Europe since the nineties. They have been in the focus of clinicians interest for years because of their biological effects. Mechanism of action of these hallucinogens, both Psilocin and Psilocibin, is based on the physiological structure similarity to human neurotransmitters as serotonin and catecholamines. One of the previous works indicated the possibility of the cardiotoxic action of the Psilocibin mushroom, effecting in anoxemic heart laesure. To verify the hypothesis of the Psilocibin-like myocardial damage wide experimental programme was designed. In the present work we introduce some results concerning magnesium, calcium, natrium, kalium and chloride plasma concentration in rats subjected subchronicly to psilocin and phenylethylamine. Basing on the obtained results, it can be stated that subchronic intoxication with natural hallucinogens may disturb magnesium balance without significantly effecting other microelements.

Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

PubMed

Strassman, R J; Qualls, C R; Uhlenhuth, E H; Kellner, R

1994-02-01

Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects

[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.

Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

PubMed

Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

2017-12-01

It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT 2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.

PubMed

Nichols, Charles D; Sanders-Bush, Elaine

2002-05-01

Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including hallucinations and detachment from reality. These remarkable behavioral effects have many similarities to the debilitating symptoms of neuropsychiatric disorders such as schizophrenia. The effects of hallucinogens are thought to be mediated by serotonin receptor activation; however, how these drugs elicit the unusual behavioral effects remains largely a mystery, despite much research. We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain. These studies represent a novel approach to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.

Clinical toxicology of newer recreational drugs.

PubMed

Hill, Simon L; Thomas, Simon H L

2011-10-01

Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may

The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells

PubMed Central

Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

2016-01-01

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain. PMID:27683542

The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.

PubMed

Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

2016-01-01

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

PubMed

Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Altered consciousness states and endogenous psychoses: a common molecular pathway?

PubMed

Ciprian-Ollivier, J; Cetkovich-Bakmas, M G

1997-12-19

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats.

PubMed

Krebs-Thomson, Kirsten; Ruiz, Erbert M; Masten, Virginia; Buell, Mahalah; Geyer, Mark A

2006-12-01

The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is structurally similar to other indoleamine hallucinogens such as LSD. The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm. A series of interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg), the 5-HT(2A) antagonist M100907 (1.0 mg/kg), and the 5-HT(2C) antagonist SER-082 (0.5 mg/kg) were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) in the BPM and PPI paradigms. 5-MeO-DMT decreased locomotor activity, investigatory behavior, the time spent in the center of the BPM chamber, and disrupted PPI. All of these effects were antagonized by WAY-100635 pretreatment. M100907 pretreatment failed to attenuate any of these effects, while SER-082 pretreatment only antagonized the PPI disruption produced by 5-MeO-DMT. While the prevailing view was that the activation of 5-HT(2) receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT(1A) receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.

Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC–MS

PubMed Central

Duffau, Boris; Camargo, Cristian; Kogan, Marcelo; Fuentes, Edwar; Cassels, Bruce Kennedy

2016-01-01

Use of unauthorized synthetic drugs is a serious, forensic, regulatory and public health issue. In this scenario, consumption of drug-impregnated blotters is very frequent. For decades, blotters have been generally impregnated with the potent hallucinogen known as lysergic acid diethylamide (LSD); however, since 2013 blotter stamps with N-2 methoxybenzyl-substituted phenylethylamine hallucinogen designated as “NBOMes” have been seized in Chile. To address this issue with readily accessible laboratory equipment, we have developed and validated a new HPTLC method for the identification and quantitation of 25-C-NBOMe in seized blotters and its confirmation by GC–MS. The proposed method was validated according to SWGTOX recommendations and is suitable for routine analysis of seized blotters containing 25-C-NBOMe. With the validated method, we analyzed 15 real samples, in all cases finding 25-C-NBOMe in a wide dosage range (701.0–1943.5 µg per blotter). In this situation, we can assume that NBOMes are replacing LSD as the main hallucinogenic drug consumed in blotters in Chile. PMID:27406128

Fluorescent Random Amplified Microsatellites (F-RAMS) analysis of mushrooms as a forensic investigative tool.

PubMed

Kallifatidis, Beatrice; Borovička, Jan; Stránská, Jana; Drábek, Jiří; Mills, Deetta K

2014-03-01

The capability of Fluorescent Random Amplified Microsatellites (F-RAMS) to profile hallucinogenic mushrooms to species and sub-species level was assessed. Fifteen samples of Amanita rubescens and 22 samples of other hallucinogenic and non-hallucinogenic mushrooms of the genera Amanita and Psilocybe were profiled using two fluorescently-labeled, 5'degenerate primers, 5'-6FAM-SpC3-DD (CCA)5 and 5'-6FAM-SpC3-DHB (CGA)5, which target different microsatellite repeat regions. Among the two primers, 5'-6FAM-SpC3-DHB (CGA)5 provided more reliable data for identification purposes, by grouping samples of the same species and clustering closely related species together in a dendrogram based on amplicon similarities. A high degree of intra-specific variation between the 15 A. rubescens samples was shown with both primers and the amplicons generated for all A. rubescens samples were organized into three classes of amplicons (discriminant, private, and marker) based on their individualizing potential. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories.

PubMed

Skrinska, Victor A; Gock, Susan B

2005-01-01

The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported.

Reasons for recent marijuana use in relation to use of other illicit drugs among high school seniors in the United States.

PubMed

Palamar, Joseph J; Griffin-Tomas, Marybec; Kamboukos, Dimitra

2015-01-01

Studies show that illicit cannabis (marijuana) use is related to use of other illicit drugs and that reasons for use are related to frequency of marijuana use. However, research is needed to examine whether specific reasons for marijuana use are associated with use of other illicit drugs. Data from recent marijuana-using high school seniors were examined from 12 cohorts of Monitoring the Future (Weighted n = 6481) to examine whether reasons for recent marijuana use are associated with use of eight other illicit drugs. Using "to experiment" decreased odds of reporting use of each drug and using to decrease effects of other drugs increased odds of reporting use of each drug. In multivariable models, using marijuana "to experiment" decreased the odds for reporting use of hallucinogens other than LSD and narcotics other than heroin. Using marijuana for "insight" increased the odds for use of hallucinogens other than LSD, and use due to "boredom" increased the odds for reporting use of powder cocaine and hallucinogens other than LSD. Using marijuana to increase effects of other drugs increased odds of reporting use of each of the eight drugs, and using it to decrease other drug effects increased odds of reporting use of crack, hallucinogens other than LSD, and amphetamine/stimulants. This study helped identify illicit marijuana users who are more likely to report use of other illicit drugs. Prevention efforts need to focus on students who report certain reasons for marijuana use as they may be at risk for use of other illicit drugs.

I like the old stuff better than the new stuff? Subjective experiences of new psychoactive substances.

PubMed

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

2017-02-01

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

Reasons for Recent Marijuana Use in Relation to Use of Other Illicit Drugs among High School Seniors in the United States

PubMed Central

Palamar, Joseph J.; Griffin-Tomas, Marybec; Kamboukos, Dimita

2015-01-01

Objectives Studies show that illicit cannabis (marijuana) use is related to use of other illicit drugs and that reasons for use are related to frequency of marijuana use. However, research is needed to examine whether specific reasons for marijuana use are associated with use of other illicit drugs. Methods Data from recent-marijuana-using high school seniors were examined from 12 cohorts of Monitoring the Future (Weighted N=6,481) to examine whether reasons for recent marijuana use are associated with use of eight other illicit drugs. Results Using “to experiment” decreased odds of reporting use of each drug and using to decrease effects of other drugs increased odds of reporting use of each drug. In multivariable models, using marijuana “to experiment” decreased the odds for reporting use of hallucinogens other than LSD and narcotics other than heroin. Using marijuana for “insight” increased the odds for use of hallucinogens other than LSD, and use due to “boredom” increased the odds for reporting use of powder cocaine and hallucinogens other than LSD. Using marijuana to increase effects of other drugs increased odds of reporting each of the eight drugs, and using it to decrease other drug effects increased odds of reporting use of crack, hallucinogens other than LSD, and amphetamine/stimulants. Conclusions This study helped identify illicit marijuana users who are more likely to report use of other illicit drugs. Prevention efforts need to focus on students who report certain reasons for marijuana use as they may be at risk for use of other illicit drugs. PMID:26115351

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.

Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies

PubMed Central

dos Santos, Rafael G.; Bouso, José Carlos; Hallak, Jaime E. C.

2017-01-01

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake. PMID:28540034

Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies.

PubMed

Dos Santos, Rafael G; Bouso, José Carlos; Hallak, Jaime E C

2017-04-01

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT 2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT2A and mGlu2 receptors in the adult offspring

PubMed Central

Moreno, José L.; Kurita, Mitsumasa; Holloway, Terrell; López, Javier; Cadagan, Richard; Martínez-Sobrido, Luis; García-Sastre, Adolfo; González-Maeso, Javier

2011-01-01

Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT2A receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu2/3 agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT2A and mGlu2 receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT2A receptor is up-regulated and the mGlu2 receptor is down-regulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT2A receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1 and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia. PMID:21289196

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

Snuff synergy: preparation, use and pharmacology of yopo and Banisteriopsis caapi among the Piaroa of southern Venezuela.

PubMed

Rodd, Robin

2002-01-01

Current understanding of the preparation and use of yopo, a hallucinogenic snuff made from the ground seeds of the Anadenanthera peregrina tree, has departed little from the accounts of scientists and travelers made over a century ago. Schultes and others have made refinements to these early accounts. While several scholars have drawn attention to the fact that little ethnographic work has been conducted to assess the ethnobotanical diversity and cultural framework of the snuff hallucinogen complex, few subsequent studies deal with botanical variations in preparation and use. This article contrasts historical accounts of yopo preparation with ethnographic data I have recently collected among the Piaroa of southern Venezuela to demonstrate one way in which yopo preparation and use deviates from the basic model established by Humboldt, Spruce and Safford. Piaroa shamans include B. caapi cuttings in the preparation of yopo and consume doses of B. caapi prior to snuff inhalation concomitant with the strength of visions desired for particular tasks. I argue that the combined use of yopo and B. caapi by Piaroa shamans is pharmacologically and ethnobotanically significant, and substantiates claims of the use of admixtures in snuff; further ethnographic investigation of the snuff hallucinogen complex is necessary.

Developments in harmine pharmacology--implications for ayahuasca use and drug-dependence treatment.

PubMed

Brierley, Daniel I; Davidson, Colin

2012-12-03

Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT(2A) and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

[Flashback following use of cannabis--a review].

PubMed

Fischer, J; Täschner, K L

1991-11-01

The present study tries to find an answer to the question, whether the consumption of cannabis can cause flashbacks, and, if so, under what circumstances they occur. This is of interest for the treatment, prognosis and also from the legal viewpoint. The definition of a flashback is often unclear. Empirical investigations are often not sufficiently comparable, the supplementary data are very often missing, making the evaluation of the results difficult. Self-diagnosis by the consumer is usually unsuitable for estimating the frequency and phenomenology of flashbacks. Cannabis may trigger flashbacks after consuming hallucinogenes; the probability of the occurrence of a flashback seems to increase with the amount of hallucinogenes a person has consumed. A definite correlation between the amount of hashish consumed and the occurrence of flashback does not exist. Flashbacks have also been reported after consuming cannabis alone. However, data vary regarding the frequency of such flashbacks. According to the available data they occur rarely and require a thorough differential diagnostic evaluation in each individual case. As a rule, the occurrence of a flashback may take place in cases where there is an intake of hallucinogenic drugs in the recent case history.

Stereoselective effects of MDMA on inhibition of monoamine uptake

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

Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

1986-03-05

The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of /sup 3/H-norepinephrine (NE) into hypothalamic synaptosomes and /sup 3/H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent thanmore » AMPH in inhibiting uptake of /sup 3/H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC/sub 50/ > 10/sup -5/M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM.« less

Acute Intoxication following Dimethyltryptamine Ingestion

PubMed Central

Higgs, Kristan V.; Wiegand, Timothy J.; Gorodetsky, Rachel M.

2018-01-01

Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT), a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented. PMID:29682363

The content of Psilocybin in Norwegian Psilocybe semilanceata.

PubMed

Christiansen, A L; Rasmussen, K E; Høiland, K

1981-07-01

Psilocybe semilanceata contains hallucinogenic indole alkaloids and has been used as a narcotic drug in Norway. The content of psilocybin, the major constituent in Norwegian P. semilanceata, has been investigated as well as its habitats and its distribution throughout the country. The mushroom is growing on grassy sites in most parts of Norway from the middle of August to the middle of October. The psilocybin content in dried mushrooms varied considerably, from 0.17 to 1.96%. The highest concentrations in percent was found among the smaller mushrooms whereas the content in mg was highest in larger mushrooms. The content of psilocybin makes P. semilanceata to a potent hallucinogenic drug.

Muscarinic Antagonists Free of Hallucinogenic Properties.

DTIC Science & Technology

1984-12-01

catatonic response again decreased to control levels. QNB, QNX and QNA were all potent stimulators of the limb flick response in rats. All three compounds...tested, 5.0 mg/Kg. QNA QNA interferes with the catatonic response in a manner quite similar to QNXFig. 1). The dose-response curve for QNA overlays that

Research Reports: Hallucinogens and Dissociative Drugs

MedlinePlus

... 2001;54(1):27-29. Halpern JH, Sherwood AR, Hudson JI, Yurgelun-Todd D, Pope HG Jr. ... SMA) 14-4887. NSDUH Series H-49. Winstock AR, Kaar S, Borschmann R. Dimethyltryptamine (DMT): prevalence, user characteristics ...

Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).

PubMed

Schindler, Emmanuelle A D; Dave, Kuldip D; Smolock, Elaine M; Aloyo, Vincent J; Harvey, John A

2012-03-01

After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however. Two commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model. Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection. Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor. Although DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens. Copyright © 2011 Elsevier Inc. All rights reserved.

The effect of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), pentobarbital and methaqualone on punished responding in control and 5,7-dihydroxytryptamine-treated rats.

PubMed

Commissaris, R L; Lyness, W H; Rech, R H

1981-05-01

The purpose of the present study was to determine the role of central 5-hydroxytryptamine (5-HT) neuronal systems in the effects of d-lysergic acid diethylamide (LSD), 2,5-methoxy-4-methylamphetamine (DOM), pentobarbital (PB) and methaqualone (MQ) on punished responding in rats. Water-deprived rats were trained to drink from a tube that was electrified at intervals (variable interval 21 sec; 0.03 mA current intensity), electrification being signalled by a tone. In daily 10-min control sessions, these animals accepted a relatively constant number of shocks; water consumption was also quite stable. At maximally effective doses PB, and to a lesser extent MQ, produced large (400-600 percent of control) increases in punished responding with little decrease in water intake. Higher doses of these agents produced a significant depression of unpunished responding (water intake). The hallucinogens, on the other hand, produced only moderate (125-175 percent of control) increases in the number of shock received, yet a similar depression of unpunished responding. Selective destruction of 5-HT neurons by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine per se produced little change in the number of shocks received or water consumed in controls sessions. This destruction of 5-HT neurons failed to alter the effects of PB or MQ on punished or unpunished responding. The increase in punished responding produced by the hallucinogens, however, was blocked by this destruction of 5-HT neurons. Furthermore, the capacity of the hallucinogens to decrease water intake was significantly potentiated by the neurotoxin pretreatment. These data demonstrate that the effects of the hallucinogens LSD and DOM on conditioned suppression are quite different from those of PB and MQ, and that this difference may be due to the extent of 5-HT involvement in the effects of these agents.

Psilocybin--summary of knowledge and new perspectives.

PubMed

Tylš, Filip; Páleníček, Tomáš; Horáček, Jiří

2014-03-01

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

4 CFR 25.8 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2014 CFR

2014-01-01

... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is being...

4 CFR 25.8 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2011 CFR

2011-01-01

... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is being...

4 CFR 25.8 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2012 CFR

2012-01-01

... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is being...

4 CFR 25.8 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2010 CFR

2010-01-01

... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is being...

4 CFR 25.8 - Alcoholic beverages and narcotics.

Code of Federal Regulations, 2013 CFR

2013-01-01

... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is being...

Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase-1, C/EBP-beta and ILAD-1, a novel gene with homology to arrestins.

PubMed

Nichols, Charles D; Sanders-Bush, Elaine

2004-08-01

We recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression patterns of a new collection of three genes increased in expression by acute LSD administration. These genes were identified through additional screens of Affymetrix DNA microarrays and examined in experiments to assess dose-response, time course and the receptor mediating the expression changes. The first induced gene, C/EBP-beta, is a transcription factor. The second gene, MKP-1, suggests that LSD activates the MAP (mitogen activated protein) kinase pathway. The third gene, ILAD-1, demonstrates sequence similarity to the arrestins. The increase in expression of each gene was partially mediated through LSD interactions at 5-HT2A (serotonin) receptors. There is evidence of alternative splicing at the ILAD-1 locus. Furthermore, data suggests that various splice isoforms of ILAD-1 respond differently at the transcriptional level to LSD. The genes thus far found to be responsive to LSD are beginning to give a more complete picture of the complex intracellular events initiated by hallucinogens.

21 CFR 862.3870 - Cannabinoid test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma... cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use. (b...

Mushrooms

MedlinePlus

... high potential for abuse and serve no legitimate medical purpose. Possession or use of hallucinogenic mushrooms is punishable by fines and jail time. Reviewed by: Steven Dowshen, ... (Ecstasy) View more ...

A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation.

PubMed

Sklerov, Jason; Levine, Barry; Moore, Karla A; King, Theodore; Fowler, David

2005-01-01

A case of a 25-year-old white male who was found dead the morning after consuming herbal extracts containing beta-carbolines and hallucinogenic tryptamines is presented. No anatomic cause of death was found at autopsy. Toxicologic analysis of the heart blood identified N,N-dimethyltryptamine (0.02 mg/L), 5-methoxy-N,N-dimethyltryptamine (1.88 mg/L), tetrahydroharmine (0.38 mg/L), harmaline (0.07 mg/L), and harmine (0.17 mg/L). All substances were extracted by a single-step n-butyl chloride extraction following alkalinization with borate buffer. Detection and quantitation was performed using liquid chromatography-electrospray mass spectrometry. The medical examiner ruled that the cause of death was hallucinogenic amine intoxication, and the manner of death was undetermined.

Family Checkup: Positive Parenting Prevents Drug Abuse

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Comorbidity

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Code of Federal Regulations, 2013 CFR

2013-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited...

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Code of Federal Regulations, 2012 CFR

2012-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited...

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Code of Federal Regulations, 2011 CFR

2011-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited...

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Code of Federal Regulations, 2010 CFR

2010-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited...

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Code of Federal Regulations, 2014 CFR

2014-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited...

The Changing Drug Culture: Emerging Drugs of Abuse and Legal Highs.

PubMed

Albertson, Timothy E; Chenoweth, James A; Colby, Daniel K; Sutter, Mark E

2016-02-01

In recent years, there has been a large increase in the number of synthetic drugs used recreationally. One class of drugs is synthetic cannabinoids, which are sprayed onto herbal preparations and marketed under names such as K2 and spice. Others include amphetaminelike compounds, such as cathinones (eg, bath salts) and methylenedioxymethamphetamine (MDMA) (eg, ecstasy, Molly). New hallucinogens, such as Bromo-Dragonfly, and hallucinogens that have been used for centuries, such as Salvia divinorum, also are gaining popularity. Because these substances are sold labeled as not for human consumption and because the chemicals in them frequently change, they often are unregulated, and many users consider them legal, although they are not. Their use often goes undetected because testing for them is not included in routine drug screening. Nonetheless, these substances can be associated with significant toxicities, often because their concentrations are unpredictable. Adverse effects of synthetic cannabinoids include psychosis and other effects. Amphetaminelike drugs have stimulant effects and can cause hyponatremia and seizures. The new hallucinogens can cause serious vasoconstriction with ischemia. Clinicians, especially those working with adolescents and young adults (ie, the main users of these drugs), should be aware of these new substances and counsel patients about their adverse effects. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

[Non-delirious toxic psychoses in children (author's transl)].

PubMed

Eggers, C

1975-01-01

There is an increasing occurrence of drug-intoxications in infancy, thus psychopathological changes due to intoxication also occur more frequently in children. 6 children were described with cases of acute and reversible toxic psychoses whose--mainly visual--hallucinations together with conditions of excitation and hyperactivity were the most striking features of the psychopathological picture; in contrast to the more frequent delirious confusion (delirium) disturbances of consciousness and orientation were missing. The phenomenological characteristics of halucinosis in children-a condition so far not specified in the case of infants and children-have been elaborated with regard to other psychotic phenomena during infancy and adult age. Relevant neurophysiological and psychodevelopmental findings lead to the following four theorems: 1. Drugs with hallucinotic effects facilitate the occurrence of "internal" pictures independent of external perceptions which are described phenomenologically as hallucinations. This theory is based on the fact that hallucinogenic drugs intensify the electrical potentials which are evoked by optic stimulation in the visual area, while an intracortical impulse propagation is inhibited. 2. A change in emotion either caused by situation or by exogenous or endogenous factors facilitates the development of hallucinations, especially if emotions dominate to such a degree that rational control of reality is being suppressed. Since hallucinogenic drugs exert their effects not only on the sensory system but also on brain structures which influence directly or indirectly emotional functions, hallucinations might also be evoked via this mechanism. 3. Brain stem has-apart from its importance in emotional processes-a filter effect and a controlling function of sensoric stimuli originating in the periphery. Hallucinogenic drugs can influence this screening function and have a disinhibitory effect which cause an inundation of the brain cortex by

MDMA (Ecstasy/Molly)

MedlinePlus

... and e-Cigarettes Will Protect Public Health Research Report MDMA (Ecstasy) Abuse Describes the science behind MDMA ( ... prevention and treatment of MDMA. Read more Research Report Hallucinogens and Dissociative Drugs Offers the latest research ...

Research Reports: Inhalants

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... are appropriately concerned about illicit drugs such as marijuana, cocaine, and LSD, they often ignore the dangers ...

Inhalants

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

NIDA Notes

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... were more likely to misuse opioid analgesics. Why Marijuana Displeases Basic Science , Published March 2018 This study ...

Cocaine

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... The Brain & the Actions of Cocaine, Opioids and Marijuana The first in a 5-part series, offers ...

Drugged Driving

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... in the past year. Middle Figure: Driving after marijuana use is more common than driving after alcohol ...

Teens Mix Prescription Opioids with Other Substances

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... least one other substance in the past year. Marijuana and alcohol were the most common (58.5% ...

Substance Use in Women and Men

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Text Description of Infographic Figure 1: Differences in Marijuana Use Disorder Women: develop disorder more quickly 1 ...

How Can Prescription Drug Addiction Be Treated?

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Principles of Substance Abuse Prevention for Early Chil... Marijuana: Facts Parents Need to Know Marijuana: Facts for ...

Brief Intervention Helps Adolescents Curb Substance Use

MedlinePlus

... Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines ... Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the-Counter ...

Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the- ...

Expanded HIV Screening Projected to Decrease Spread of the Virus

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the- ...

Although Relatively Few, "Doctor Shoppers" Skew Opioid Prescribing

MedlinePlus

... Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine and E- ... Fentanyl GHB Hallucinogens Heroin Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids ...

Prenatal Methamphetamine Exposure Linked with Problems

MedlinePlus

... Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine and E- ... Fentanyl GHB Hallucinogens Heroin Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids ...

Plant toxins that affect nicotinic acetylcholine receptors: A review

USDA-ARS?s Scientific Manuscript database

Plants produce wide variety of chemical compounds termed secondary metabolites that are not involved in basic metabolism, photosynthesis or reproduction. These compounds are used as flavors, fragrances, insecticides, dyes, hallucinogens, nutritional supplements, poisons, and pharmaceutical agents. ...

Drug abuse first aid

MedlinePlus

... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

PubMed

Frecska, Ede; Szabo, Attila; Winkelman, Michael J; Luna, Luis E; McKenna, Dennis J

2013-09-01

N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.

Serotonin research: contributions to understanding psychoses.

PubMed

Geyer, Mark A; Vollenweider, Franz X

2008-09-01

The history of serotonin research is closely related to the study of hallucinogenic drugs that function as agonists at serotonin-2A receptors. The fundamental idea that psychotic states seen in psychiatric disorders such as schizophrenia might be attributable, in part, to abnormalities in serotonergic systems began with the almost simultaneous discovery of lysergic acid diethylamide (LSD), psilocybin and serotonin. Sixty years of study have confirmed early speculations regarding the important relationship between serotonin and both drug-induced and disorder-based psychotic states. Now, modern biochemical, pharmacological, behavioral, neuroimaging, genetic and molecular biological sciences are converging to understand how serotonergic systems interact with other monoaminergic and glutamatergic systems to modulate states of consciousness and contribute to psychotic disorders such as the group of schizophrenias. This review summarizes experimental assessments of the serotonergic hallucinogen model psychosis in relation to the serotonin hypothesis of schizophrenia.

Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives.

PubMed

Nakagawasai, Osamu; Arai, Yuichiro; Satoh, Shin-etsu; Satoh, Nobunori; Neda, Mitsuro; Hozumi, Masato; Oka, Ryusho; Hiraga, Hajime; Tadano, Takeshi

2004-01-01

It is well known that head-twitch response (HTR) in mice represents hallucinations, since administration of lysergic acid diethylamide (LSD) produces hallucinations in humans, and the HTR in mice is induced by administration of LSD as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5-HT)2A receptors. In this paper, we review the mechanisms of HTR induced by various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser, hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by HTR-inducers is significantly enhanced by combined treatment with a non-selective form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO activity and HTR caused by these drugs (especially, alpha-methylated analogous compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine and p-hydroxyamphetamine) is presented in detail.

The Psychedelic Experience: High Adolescence

ERIC Educational Resources Information Center

Chunko, John A.

1972-01-01

The purpose of this study is to present a progressive understanding of the use of hallucinogenic drugs, particularly LSD, including a brief physiological tangent, in order to elucidate the ramifications of tripping,'' as it is colloquially referred to. (Author)

Unmanned Aircraft Pilot Medical Certification Requirements

DTIC Science & Technology

2007-02-01

Security Classif. (of this page) 21. No. of Pages 22. Price Unclassified Unclassified 14 Form DOT F 1700.7 (8-72) Reproduction of completed...and hypnotics , anxiolytics, marijuana, cocaine, opiods, amphetamines, hallucinogens, and other psychoactive drugs or chemicals.) Disqualifying

Project CHECO Southeast Asia Report. Drug Abuse in Southeast Asia

DTIC Science & Technology

1975-01-01

lysergic acid diethylamide (LSD), mescaline, demethoxy- amphetamine (STP), and psilocybin . c. Narcotics - Any opiates or cocaine, including their synthetic...8217.amine hailuciL,ogen senses Mescalin Mesc 3, 4, 5 trineth Hallucinogen Swallowed Exhilaration; oxyphenethylamine distortion of senses Psilocybin 8 (2

Substance use - LSD

MedlinePlus

Substance abuse - LSD; Drug abuse - LSD; Drug use - LSD; Lysergic acid diethylamide; Hallucinogen - LSD ... LSD is a mind-altering drug. This means it acts on your brain (central nervous system) and changes your mood, behavior, and the way you relate to ...

Medicinal Mushrooms in Guatemala.

PubMed

Sommerkamp, Yvonne; Paz, Ana Margarita; Guzmán, Gastón

2016-01-01

Guatemala, located in Central America, has a long and rich history in the traditional use of edible, medicinal, and hallucinogenic mushrooms. This article describes the use of these mushrooms and presents studies on the scientific validation of native and foreign species.

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

Personnel Security Research - Prescreening and Background Investigations

DTIC Science & Technology

1986-06-01

military unit, base, station, ship, or aircraft nf a controlled substance with the intent to distribute. Hallucinogens/ Psychedelics . A group of...and psychedelic amphetamine variants (STP, MDA). Although a unique drug, for purposes of this certificate phencyclidine (PCP) will be labeled in this

Medical Readings on Drug Abuse.

ERIC Educational Resources Information Center

Byrd, Oliver E.

Summaries are presented of over 150 articles in the recent medical and psychiatric literature. Topics covered are: effects of drugs, tobacco, alcohol, drugs used in medicine, vapor sniffing, marijuana, barbiturates, tranquilizers, amphetamines, methamphetamine, lysergic acid diethylamide, other hallucinogens, heroin and the opiates, psychiatric…

Drug and Substance Abuse

MedlinePlus

... Some older adults also abuse illegal drugs, including marijuana, cocaine, hallucinogens, and injected narcotics. Some people misuse more than one substance. Many older adults who become addicted to drugs also have another serious medical condition, such as chronic pain or a mental ...

Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

PubMed

Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

2015-04-01

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. 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.

Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers.

PubMed

Gouzoulis-Mayfrank, E; Heekeren, K; Neukirch, A; Stoll, M; Stock, C; Obradovic, M; Kovar, K-A

2005-11-01

Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and N,N-dimethyltryptamine (DMT). However, so far, the psychological profiles of the two types of hallucinogenic drugs have never been studied directly in an experimental within-subject design. Fifteen healthy volunteers were included in a double-blind, cross-over study with two doses of the serotonin 5-HT2A agonist DMT and the glutamate N-methyl-D-aspartate (NMDA) antagonist (S)-ketamine. Data are reported for nine subjects who completed both experimental days with both doses of the two drugs. The intensity of global psychological effects was similar for DMT and (S)-ketamine. However, phenomena resembling positive symptoms of schizophrenia, particularly positive formal thought disorder and inappropriate affect, were stronger after DMT. Phenomena resembling negative symptoms of schizophrenia, attention deficits, body perception disturbances and catatonia-like motor phenomena were stronger after (S)-ketamine. The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.

[Selected Readings for the Professional Working with Drug Related Problems.

ERIC Educational Resources Information Center

Wisconsin Univ., Madison.

A bibliography of selected readings compiled at the University of Wisconsin for the National Drug Education Training Program. These selected readings include information on narcotics, amphetamines, mescaline, psilogybin, hallucinogens, LSD, barbiturates, alcohol, and other stimulants. The intended user of this bibliography is the professional…

Development of Computer-Supported Assessment and Treatment Consultation for Emotional Crises (CATCEC) for a Submarine Environment.

DTIC Science & Technology

1986-03-01

SCHIZOPHRENIC DISORDER Amphetamine Delusional Disorder PARANOID DISORDER Cannabis Delusional Disorder Hallucinogen Delusional Disorder BRIEF REACTIVE...Intoxication Borderline Personality Disorder Cocaine Intoxication Histrionic Personality Disorder Caffeine Intoxication Narcissistic Personality Disorder... Cannabis Intoxication Dependent Personality Disorder ON, Inhalant Intoxication Schizoid Personality Disorder Minor Tranquilizer Intoxication Compulsive

Family Medicine Curriculum Guide to Substance Abuse.

ERIC Educational Resources Information Center

Liepman, Michael R., Ed.; And Others

This curriculum guide on substance abuse is intended for teachers of family medicine. Comments, learning objectives, teaching hints, and evaluations of knowledge are provided for each area in all chapters. Chapter 1 focuses on the pharmacology of commonly abused drugs including depressants, opioids, stimulants, hallucinogens, inhalants, and…

Emotional and Behavioral Disturbances in Adolescents Involved in Witchcraft and Satanism.

ERIC Educational Resources Information Center

Burket, Roger C.; And Others

1994-01-01

Examined inpatient medical records of 157 consecutive adolescent admissions to private psychiatric hospital. Ten patients with interest in witchcraft and Satanism had significantly more diagnoses of identity disorder, alcohol abuse, and hallucinogen abuse. One-half reported history of self-mutilation. Found no significant difference in criminal…

Substance Use of Creatively Talented Adults.

ERIC Educational Resources Information Center

Kerr, Barbara; And Others

1991-01-01

A survey of 22 writers, 27 artists, and 12 musicians compared their substance use (caffeine, nicotine, alcohol, marijuana, hallucinogens, cocaine, tranquilizers, stimulants, and narcotics) with that of a control group. In general, no significant intergroup differences were found. Older participants used marijuana less than younger participants.…

Attributions for Abstinence from Illicit Drugs by University Students

ERIC Educational Resources Information Center

Rosenberg, Harold; Baylen, Chelsea; Murray, Shanna; Phillips, Kristina; Tisak, Marie S.; Versland, Amelia; Pristas, Erica

2008-01-01

Aim: To assess college students' attributions for abstinence from alcohol and illicit drugs. Method: We recruited 125 undergraduates to rate the degree to which each of 41 listed reasons influenced their abstention from six specific substances (alcohol, MDMA/ecstasy, inhalants, cocaine, marijuana, and hallucinogens). Findings: Internal consistency…

Virtual Reality and Cellular Phones as a Complementary Intervention for Veterans with PTSD and Substance Use Disorders

DTIC Science & Technology

2013-12-01

met criteria for primary alcohol dependence (9 in PE, and 10 in PE-VR), 6 (15.0%) met criteria for primary cannabis dependence (3 in each...Sedative 0% 0% Cannabis 20% 10% Stimulant 0% 0% Opioid 0% 5% Cocaine 5% 20% Hallucinogen 0% 0% Other 25

Psychedelic Research: Obstacles and Values

ERIC Educational Resources Information Center

Clark, Walter Houston

1975-01-01

Author considered the proper use of the LSD-type drugs, variously called hallucinogenic, mind-altering, mind-revealing, or psychedelic, and sampled the views of responsible researchers on the use of these drugs for mental health and for the study of the human mind and development. (Author/RK)

76 FR 17778 - Control of Ergocristine, a Chemical Precursor Used in the Illicit Manufacture of Lysergic Acid...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... substance lysergic acid diethylamide (LSD). This rule is being finalized as proposed. Therefore, handlers of... INFORMATION: Background Lysergic acid diethylamide (LSD) is a synthetic schedule I hallucinogen. It is the... clarity, but reduced ability to control what is experienced. Illicit Production of LSD LSD has been...

48 CFR 245.7310-5 - Controlled substances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (Bureau of Narcotics and Dangerous Drugs) to buy controlled substances as a medical practitioner, dealer... hallucinogenic drugs, shall be subject to the following special conditions: (a) Controlled Substances. Bids will... represents and warrants that it is registered under The Comprehensive Drug Abuse Prevention and Control Act...

Class identity assignment for amphetamines using neural networks and GC-FTIR data

NASA Astrophysics Data System (ADS)

Gosav, S.; Praisler, M.; Van Bocxlaer, J.; De Leenheer, A. P.; Massart, D. L.

2006-08-01

An exploratory analysis was performed in order to evaluate the feasibility of building of neural network (NN) systems automating the identification of amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical and forensic purposes. A first neural network system was built to distinguish between amphetamines and nonamphetamines. A second, more refined system, aimed to the recognition of amphetamines according to their toxicological activity (stimulant amphetamines, hallucinogenic amphetamines, nonamphetamines). Both systems proved that discrimination between amphetamines and nonamphetamines, as well as between stimulants, hallucinogens and nonamphetamines is possible (83.44% and 85.71% correct classification rate, respectively). The spectroscopic interpretation of the 40 most important input variables (GC-FTIR absorption intensities) shows that the modeling power of an input variable seems to be correlated with the stability and not with the intensity of the spectral interaction. Thus, discarding variables only because they correspond to spectral windows with weak absorptions does not seem be not advisable.

75 FR 37301 - Exempt Chemical Mixtures Containing Gamma-Butyrolactone

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... their central nervous system (CNS) depressant effect. An overdose from GBL or GHB may result in... the central nervous system that is substantially similar to or greater than the stimulant, depressant, or hallucinogenic effect on the central nervous system of a controlled substance in schedule I or II...

Close Call: Magic.

ERIC Educational Resources Information Center

Journal of Adventure Education and Outdoor Leadership, 1993

1993-01-01

Staff at a residential camp for high-risk youth dealt with campers eating potentially lethal hallucinogenic mushrooms by eliminating the mushrooms instead of confronting the group and thereby jeopardizing the relationship between staff and campers. Analyzes the situation and provides suggestions for handling similar incidents in the future. (LP)

Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

PubMed

Buckholtz, N S; Zhou, D F; Freedman, D X; Potter, W Z

1990-04-01

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

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

Excess mortality among people who report lifetime use of illegal drugs in the United States: A 20-year follow-up of a nationally representative survey.

PubMed

Walker, Elizabeth Reisinger; Pratt, Laura A; Schoenborn, Charlotte A; Druss, Benjamin G

2017-02-01

The purpose of this study was to determine the mortality risks, over 20 years of follow-up in a nationally representative sample, associated with illegal drug use and to describe risk factors for mortality. We analyzed data from the 1991 National Health Interview Survey, which is a nationally representative household survey in the United States, linked to the National Death Index through 2011. This study included 20,498 adults, aged 18-44 years in 1991, with 1047 subsequent deaths. A composite variable of self-reported lifetime illegal drug use was created (hierarchical categories of heroin, cocaine, hallucinogens/inhalants, and marijuana use). Mortality risk was significantly elevated among individuals who reported lifetime use of heroin (HR=2.40, 95% CI: 1.65-3.48) and cocaine (HR=1.27, 95% CI: 1.04-1.55), but not for those who used hallucinogens/inhalants or marijuana, when adjusting for demographic characteristics. Baseline health risk factors (smoking, alcohol use, physical activity, and BMI) explained the greatest amount of this mortality risk. After adjusting for all baseline covariates, the association between heroin or cocaine use and mortality approached significance. In models adjusted for demographics, people who reported lifetime use of heroin or cocaine had an elevated mortality risk due to external causes (poisoning, suicide, homicide, and unintentional injury). People who had used heroin, cocaine, or hallucinogens/inhalants had an elevated mortality risk due to infectious diseases. Heroin and cocaine are associated with considerable excess mortality, particularly due to external causes and infectious diseases. This association can be explained mainly by health risk behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats.

PubMed

Levant, Beth; Pazdernik, Thomas L

2004-04-02

Ibogaine, a hallucinogenic indole alkaloid, has been proposed as a treatment for addiction to opioids and other drugs of abuse. The mechanism for its putative anti-addictive effects is unknown. In this study, the effects of ibogaine on local cerebral glucose utilization (LCGU) were determined in freely moving, drug-naive, or morphine-dependent adult, male, Sprague-Dawley rats using the [(14)C]2-deoxyglucose (2-DG) method. Morphine-dependent rats were treated with increasing doses of morphine (5-25 mg/kg, s.c., b.i.d.) and then maintained at 25 mg/kg (b.i.d.) for 4-7 days. For the 2-DG procedure, rats were injected with saline or ibogaine (40 mg/kg, i.p.). 2-DG was administered 1 h after administration of ibogaine. The rate of LCGU was determined by quantitative autoradiography in 46 brain regions. In drug-naive animals, ibogaine produced significant increases in LCGU in the parietal, cingulate, and occipital cortices and cerebellum compared to controls consistent with its activity as a hallucinogen and a tremorogen. Morphine-dependent rats had only minor alterations in LCGU at the time assessed in this experiment. However, in morphine-dependent animals, ibogaine produced a global decrease in LCGU that was greatest in brain regions such as the lateral and medial preoptic areas, nucleus of the diagonal band, nucleus accumbens shell, inferior colliculus, locus coeruleus, and flocculus compared to morphine-dependent animals treated with saline. These findings indicate that ibogaine produces distinctly different effects on LCGU in drug-naive and morphine-dependent rats. This suggests that different mechanisms may underlie ibogaine's hallucinogenic and anti-addictive effects.

Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain.

PubMed

Hungen, K V; Roberts, S; Hill, D F

1975-08-22

Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and

Students and Drugs at NCSU: 1977-1978 Report.

ERIC Educational Resources Information Center

Fuller, Earl H.

A survey conducted in 1977 at North Carolina State University on drugs was designed to measure usage rates for four types of drugs: marijuana, hallucinogens (such as LSD, mescaline, and psilocybin); amphetamines and barbituates; and narcotics (heroin, opium, and morphine). The questionnaire was also designed to determine student attitudes on…

The Pedagogical Implications of a Futures Program in Geography.

ERIC Educational Resources Information Center

McDaniel, Robert

The intent of this paper is to provide geography educators and researchers with insights into creating a "geography of the future." Among the insights of major interest to geographers (including students, teachers, researchers, and other professional geographers) are that altered states of consciousness (such as often brought on by hallucinogens)…

Mind Over Matter: The Brain's Response to Drugs. Teacher's Guide.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

This teacher's guide aims to develop an understanding among students grades 5 through 9 of the physical reality of drug use. Contents include: (1) "Brain Anatomy"; (2) "Nerve Cells and Neurotransmission"; (3) "Effects of Drugs on the Brain"; (4) "Marijuana"; (5) "Opiates"; (6) "Inhalants"; (7) "Hallucinogens"; (8) "Steroids"; (9) "Stimulants";…

Entering Adulthood: Examining Drugs and Risks. A Curriculum for Grades 9-12. Contemporary Health Series. [Teacher's Guide and] Student Workbook.

ERIC Educational Resources Information Center

Giarratano, Susan; Evans, Dale

This curriculum guide for high-school students presents in-depth coverage of the full range of content related to drugs, including tobacco, alcohol, marijuana, cocaine, narcotics, and hallucinogens. It is part of a series designed to provide educators with the curricular tools necessary to challenge students to take personal responsibility for…

Governor's Conference on Drug Dependence and Abuse. An Occasional Paper of the Honors College.

ERIC Educational Resources Information Center

Milliken, William G.; And Others

1970-01-01

Following Governor Milliken's address, Dr. Dana Farnsworth defines the problem in terms of who's involved, to what extent, and with which drugs. His presentation focuses primarily on the motives of affluent young people who experiment with or become dependent upon hallucinogens, marihuana and amphetamines. He deals extensively with the drastically…

Drugs, Alcohol & Pregnancy.

ERIC Educational Resources Information Center

Dye, Christina

Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

[Statement on Recent Research on LSD, Marihuana, and Other Dangerous Drugs.

ERIC Educational Resources Information Center

Yolles, Stanley F.

The National Institute of Mental Health is continuing support of several studies designed to measure trends in the use of hallucinogens. Indications are that the evidence for persisting psychological and birth defect damage from chronic LSD use is minimal. Though they are a continuing problem, admissions to psychiatric units of persons with "bad…

Illicit Drug Use in a Community-Based Sample of Heterosexually Identified Emerging Adults

ERIC Educational Resources Information Center

Halkitis, Perry N.; Manasse, Ashley N.; McCready, Karen C.

2010-01-01

In this study we assess lifetime and recent drug use patterns among 261 heterosexually identified 18- to 25-year-olds through brief street intercept surveys conducted in New York City. Marijuana, hallucinogens, powder cocaine, and ecstasy were the most frequently reported drugs for both lifetime and recent use. Findings further suggest significant…

Associations between University Students' Reported Reasons for Abstinence from Illicit Substances and Type of Drug

ERIC Educational Resources Information Center

Rosenberg, Harold; Bonar, Erin E.; Pavlick, Michelle; Jones, Lance D.; Hoffmann, Erica; Murray, Shanna; Faigin, Carol Ann; Cabral, Kyle; Baylen, Chelsea

2012-01-01

We recruited 211 undergraduates to rate the degree to which each of 34 listed reasons for not taking drugs had influenced their abstinence from MDMA/ecstasy, cocaine, marijuana, and hallucinogens. Participants rated reasons such as personal and family medical histories, religion, and physiological consequences of drug use as having little or no…

LSD Now: 1973

ERIC Educational Resources Information Center

Chunko, John A.

1973-01-01

LSD NOW is a nationwide, statistical survey and analysis of hallucinogenic drug use by individuals presently in formal educational surroundings. Analysis, concentrating on the extent and rationale related to the use of such drugs, now offers a deeper and more meaningful understanding of a particular facet of the drug culture. This understanding…

Highlights from Drug Use Among American High School Students 1975-1977.

ERIC Educational Resources Information Center

Johnston, Lloyd D.; And Others

The current prevalence of drug use among American high school seniors and the trends in use since 1975 are the two major topics treated. Also reported are prevailing attitudes and beliefs among seniors concerning various types of drug use. Eleven separate classes of drugs are distinguished: marihuana (including hashish), inhalants, hallucinogens,…

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

PubMed

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

2015-03-27

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

PubMed Central

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V.; Halama, Marek; Wieczorek, Piotr P.

2015-01-01

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers. PMID:25826052

HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice.

PubMed

Holloway, Terrell; Moreno, Jose L; González-Maeso, Javier

2016-07-09

The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in some of the behavioral phenotypes in mouse models of psychosis(1,2). Consequently, investigation of structural details of the interaction between 5-HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful translational tool. As previously shown, the head-twitch response (HTR) in mice is elicited by hallucinogenic drugs and this behavioral response is absent in 5-HT2A knockout (KO) mice(3,4). Additionally, by conditionally expressing the 5-HT2A receptor only in cortex, it was demonstrated that 5-HT2A receptor-dependent signaling pathways on cortical pyramidal neurons are sufficient to elicit head-twitch behavior in response to hallucinogenic drugs(3). Finally, it has been shown that the head-twitch behavioral response induced by the hallucinogens DOI and lysergic acid diethylamide (LSD) is significantly decreased in mGlu2-KO mice(5). These findings suggest that mGlu2 is at least in part necessary for the 5-HT2A receptor-dependent psychosis-like behavioral effects induced by LSD-like drugs. However, this does not provide evidence as to whether the 5-HT2A-mGlu2 receptor complex is necessary for this behavioral phenotype. To address this question, herpes simplex virus (HSV) constructs to express either mGlu2 or mGlu2ΔTM4N (mGlu2/mGlu3 chimeric construct that does not form the 5-HT2A-mGlu2 receptor complex) in the frontal cortex of mGlu2-KO mice were used to examine whether this GPCR heteromeric complex is needed for the behavioral effects induced by LSD-like drugs(6).

Drug Use among American High School Students, College Students, and Other Young Adults. National Trends Through 1985.

ERIC Educational Resources Information Center

Johnston, Lloyd D.; And Others

Drug use and related attitudes of U.S. high school seniors from the graduating classes of 1975-1985 and young adults in their late teens and early- to mid-twenties were studied, as part of an ongoing research project. Eleven classes of drugs were assessed: marijuana (including hashish), inhalants, hallucinogens, cocaine, heroin, other natural and…

What Will Happen if . . . A Programmed Instruction Course on Drugs and Their Effects.

ERIC Educational Resources Information Center

Health Services and Mental Health Administration (DHEW), Bethesda, MD.

Developed by the National Institute of Mental Health, this booklet offers a programed instruction course on drugs and their effects. The purpose of the text is to learn about specific drugs which are currently being used and abused by a large group of people in our society. Narcotics, stimulants, depressants, hallucinogens, and marihuana are…

A Nonpharmacologic Method for Enhancing Sleep in PTSD

DTIC Science & Technology

2015-10-01

medications include: Alcohol (during intoxication or withdrawal); cannabis (during intoxication); hallucinogens (during intoxication), phencyclidine... medications are taken solely under appropriate medical supervision, this criterion is not considered to be met. SEDATIVE/ HYPNOTIC/ANX CANNABIS ...are taken solely under appropriate medical supervision, this criterion is not considered to be met. SEDATIVE/ HYPNOTIC/ANX CANNABIS STIMULANTS

The Association of Salvia divinorum and Psychotic Disorders: A Review of the Literature and Case Series.

PubMed

El-Khoury, Joseph; Sahakian, Nayiri

2015-01-01

The association of substance abuse and psychotic disorders is of interest to clinicians, academics, and lawmakers. Commonly abused substances, such as cannabis, cocaine, amphetamines, and alcohol, have all been associated with substance-induced psychosis. Hallucinogens can induce desired psychedelic effects and undesirable psychomimetic reactions. These are usually transient and resolve once the duration of action is over. Sometimes, these effects persist, causing distress and requiring intervention. This article focuses on the hallucinogenic substance Salvia divinorum, the use of which has been observed, particularly among youth worldwide. We present background information based on a review of the literature and on our own clinical encounters, as highlighted by two original case reports. We hypothesize that consumption of Salvia divinorum could be associated with the development of psychotic disorders. We propose that clinicians routinely inquire about the use of Salvia in patients with substance use disorders or psychotic illnesses. More research is required to assess any relationship between Salvia divinorum and psychosis. Additionally, we advocate increased public and medical awareness of this substance and other emerging drugs of abuse.

[Ritual use of Anadenanthera seeds among South America natives].

PubMed

Carod-Artal, F J; Vázquez Cabrera, C B

2007-01-01

Several South-American native societies snuff psychoactive seeds in magic-religious rituals since ancient times. To describe archeological, historical and ethnographical evidences regarding the ritual use of vilca or yopo (Anadenanthera sp). Anadenanthera seeds were used in South America 3,000 years ago. Archeological studies found vilca seeds in funerary tombs from 1,000 BC in the north of Chile and Argentina; ceramics and snuff tubes were found in San Pedro de Atacama archeological sites from the same data, and in Tiwanaku ceremonial center in Bolivian Altiplano. Today, Anadenanthera sp is used by several native groups in Orinoco basin, where is known as yopo, and in the Brazilian and Colombian Amazon. Hallucinogenic effect is due to the presence of methyl-tryptamine derivatives. Most snuff is prepared from the roasted and powdered seeds, vegetable ash and/or lime obtained from shells. Archeological and ethnographical data suggest that vilca was used and is still used by native shamans as a sacred seed in South America, due to its hallucinogenic effects.

Ergot Alkaloids and their Hallucinogenic Potential in Morning Glories.

PubMed

Steiner, Ulrike; Leistner, Eckhard

2018-03-02

Naturally occurring and semisynthetic ergot alkaloids play a role in health care or as recreational drugs in Western and indigenous Mexican societies. Evidence is summarized that ergot alkaloids present in Central American Convolvulaceae like Turbina corymbosa, Ipomoea violacea , and Ipomoea asarifolia are colonized by different species of a newly described clavicipitaceous fungal genus named Periglandula . The fungi are associated with peltate glandular trichomes on the adaxial leaf surface of its host plants. The Periglandula fungi are not yet culturable in vitro but were demonstrated to have the capacity to synthesize ergot alkaloids. The alkaloids do not remain in the fungal mycelium but are translocated via the glandular trichomes into their plant host. Both fungi and host benefit from a symbiotic lifestyle. In evolutionary terms the alkaloid biosynthetic gene cluster in the Periglandula/Ipomoea symbiosis is likely to have a conserved (basic) structure while biosynthetic ergot gene clusters within the genera Claviceps and Epichloe were under ecological selection for alkaloid diversification. Georg Thieme Verlag KG Stuttgart · New York.

Journal of Special Operations Medicine, Volume 2, Edition 3

DTIC Science & Technology

2002-01-01

propranolol, methyldopa, guanethidine Thyroid hormones--thyroxine Hallucinogens--LSD Salicylates, barbiturates General anesthetics --halothane...Alcohol LSD, lysergic acid diethylamide. Volume 2, Edition 3 / Summer 02 21 must be available and palatable , and water intake must be monitored. Water... palatability are controversial. High sugar solutions may impede water absorption. Salt losses should be made up (during the first 2 weeks in a hot

Drug Intoxicated Irregular Fighters: Complications, Dangers, and Responses

DTIC Science & Technology

2008-03-01

manufactured . The result is the use of marijuana, khat, hallucinogenic mush- rooms, cocaine, heroin, methamphetamine, and looted pharmaceuticals to...drugs in today’s wars falls into at least one of four categories: traditional, transshipped, looted, and manufactured . These categories are not...also be attained by looting them from pharmacies, clinics, and hospitals. These are prescrip- tion drugs manufactured by pharmaceutical companies 10

Chemistry and Structure-Activity Relationships of Psychedelics.

PubMed

Nichols, David E

2018-01-01

This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT 2A receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT 2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT 2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT 2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.

LSD Flashbacks - The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports.

PubMed

G Lerner, Arturo; Goodman, Craig; Rudinski, Dmitri; Lev-Ran, Shaul

2014-01-01

A side effect associated with the use of synthetic hallucinogens such as lysergic acid diethylamide-(LSD) is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite absence of recent use. These are commonly referred to as "flashbacks" or Hallucinogen Persisting Perception Disorder (HPPD). Here we present two cases of patients with a prior history of LSD use who turned to psychiatric consultation following brief episodes of HPPD. Surprisingly, in both cases new visual imagery appeared during episodes of flashbacks which was not experienced during primary LSD use. Both subjects reported the ability to discern between LSD-associated visual disturbances and new visual imagery. This phenomenon did not cause functional impairment and in both cases caused gradual concern due to its persistence. Both patients refused medical treatment and continued psychiatric follow-up. At one year follow-up both patients reported almost complete spontaneous remission. To the best of our knowledge these are the first reported cases of LSD-related benign flashbacks in which new imagery is experienced. Reasons for this reversible and apparently harmless side effect are proposed. Conclusions from case reports should be taken with caution.

ANN expert system screening for illicit amphetamines using molecular descriptors

NASA Astrophysics Data System (ADS)

Gosav, S.; Praisler, M.; Dorohoi, D. O.

2007-05-01

The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

PubMed Central

Béïque, Jean-Claude; Imad, Mays; Mladenovic, Ljiljana; Gingrich, Jay A.; Andrade, Rodrigo

2007-01-01

Classic hallucinogens such as lysergic acid diethylamide are thought to elicit their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT2AR). One likely site for these effects is the prefrontal cortex (PFC). Previous studies have shown that activation of 5-HT2ARs in this region results in a robust increase in spontaneous glutamatergic synaptic activity, and these results have led to the widely held idea that hallucinogens elicit their effect by modulating synaptic transmission within the PFC. Here, we combine cellular and molecular biological approaches, including single-cell 5-HT2ARs inactivation and 5-HT2AR rescue over a 5-HT2AR knockout genetic background, to distinguish between competing hypotheses accounting for these effects. The results from these experiments do not support the idea that 5-HT2ARs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that 5-HT2ARs facilitate intrinsic networks within the PFC. Consistent with this idea, we locate a discrete subpopulation of pyramidal cells that is strongly excited by 5-HT2AR activation. PMID:17535909

Cocaine and Instability in Africa: Lessons from Latin America and the Caribbean (Africa Security Brief, Number 5, July 2010)

DTIC Science & Technology

2010-07-01

however, that instability in East Africa is attracting heroin traffic (contributing to an esti- Davin O’Regan is a Research Associate at the Africa...Narcotics trafficking is not intrinsically violent. Violence within the international trade in cannabis and Ecstasy , a popular hallucinogen...70 people were killed in clashes and gun battles. Trafficking- associated violence can reach even more dangerous levels. In Mexico, traffickers fre

Effects of Psilocybe argentipes on marble-burying behavior in mice.

PubMed

Matsushima, Yoshihiro; Shirota, Osamu; Kikura-Hanajiri, Ruri; Goda, Yukihiro; Eguchi, Fumio

2009-08-01

Psilocybe argentipes is a hallucinogenic mushroom. The present study examined the effects of P. argentipes on marble-burying behavior, which is considered an animal model of obsessive-compulsive disorder. P. argentipes significantly inhibited marble-burying behavior without affecting locomotor activity as compared with the same dose of authentic psilocybin. These findings suggest that P. argentipes would be efficient in clinical obsessive-compulsive disorder therapy.

Prescreening Military Officer Candidates for High Level Security Clearances

DTIC Science & Technology

1989-06-01

the Navy’s policy on drug and alcohol abuse . 17 Applicants are restricted from acceptance into a nuclear officer program , or fields in support of the...Z1:36uCd met:iacone. vercodan, and others. DRUG ABUSE : The illegal, wrongful. or improper use of marijuana, any narcotic substance . hallucinogens, or...a. (OFFICERS PRE-COMMISSIONING PROGRAMS ) ( understand the U. S. Navy’s intolerance of substance

Personnel-General: Army Substance Abuse Program Civilian Services

DTIC Science & Technology

2001-10-15

destroyed. Additional reproduction and distribution of completed records is prohibited. c. SECTION I. IDENTIFICATION. (1) Block I. Date of Report. Enter...AMPHETAMINE B BARBITUATES C COCAINE H HALLUCINOGENS (LSD) M METHAQUALONE, SEDATIVE, HYPNOTIC , OR ANXIOLYTIC O OPIATES P PHENCYCLIDINE (PCP) T CANNABIS...Table 5–6 Codes for TABLE F (T-DIAG-CODE) Code Rejection Reason 30390 ALCOHOL DEPENDENCE 30400 OPIOID DEPENDENCE 30410 SEDATIVE, HYPNOTIC , OR ANXIOLYTIC

Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.

PubMed

Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E

1998-11-01

Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT.

Drug Abuse in the Military Impacts National Security.

DTIC Science & Technology

1988-03-30

types of drugs - cannabis , hallucinogens, opiates, stimulants, hypnotics, and cocaine. Subscores were derived for each drug, based upon the product of a...he was interviewed by medical personnel. The soldiers who were Judged to be not drug dependent continued their military service. Soldiers who were...separated as "not meeting the medical 8 fitness standards at time of entry. These separated soldiers along with all others with medical and non

Psilocybin-induced stimulus control in the rat.

PubMed

Winter, J C; Rice, K C; Amorosi, D J; Rabin, R A

2007-10-01

Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT(2A) receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT(1A/7) receptor antagonist, WAY-100635, or the DA D(2) antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT(2A) receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT(1A) receptors appears to play no role in psilocybin-induced stimulus control.

Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction

PubMed Central

Johnson, Matthew W.; Garcia-Romeu, Albert; Cosimano, Mary P.; Griffiths, Roland R.

2014-01-01

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20mg/70kg) and high (30mg/70kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of 6 previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction. PMID:25213996

Psilocybin-induced stimulus control in the rat

PubMed Central

Winter, J.C.; Rice, K.C.; Amorosi, D.J.; Rabin, R.A.

2007-01-01

Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DA D2 antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT2A receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT1A receptors appears to play no role in psilocybin-induced stimulus control. PMID:17688928

Salvia divinorum: effects and use among YouTube users.

PubMed

Lange, James E; Daniel, Jason; Homer, Kestrel; Reed, Mark B; Clapp, John D

2010-04-01

Salvia divinorum (salvia) is an intense, short-acting hallucinogenic plant gaining popularity among adolescents in the United States. There has been little scientific documentation of salvia's effects. The popular video-sharing website YouTube has received literally thousands of video-posts of people using salvia. The objective of this study was to assess the effects of salvia use through systematic observations of YouTube videos. A sample of salvia videos was obtained using the search term "salvia." The videos were further screened and only videos that captured the entire drug "trip" without video edits were included in the analyses described here (n=34). Three trained research assistants independently watched the videos and rated their observations on 42 effects in 30-s intervals. Onset of symptoms was quick (often less than 30s) and tended to dissipate within 8min. Further, there was a relationship between salvia dose and effect duration. Since salvia's effects on humans are largely undocumented, this study provides the look at users in a non-laboratory environment (e.g. self-taped videos) exhibiting impairments and behaviors consistent with this powerful hallucinogen. Also, this study demonstrates the feasibility and shortcomings of using YouTube videos to assess emerging drugs and drug effects. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.

PubMed

Dos Santos, Rafael G; Hallak, Jaime E C

2017-01-01

Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.

The subjective experience of acute, experimentally-induced Salvia divinorum inebriation.

PubMed

Addy, Peter H; Garcia-Romeu, Albert; Metzger, Matthew; Wade, Jenny

2015-04-01

This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse. © The Author(s) 2015.

Dimethyltryptamine (DMT): subjective effects and patterns of use among Australian recreational users.

PubMed

Cakic, Vince; Potkonyak, Jacob; Marshall, Alex

2010-09-01

Dimethyltryptamine (DMT) is an endogenous hallucinogen with traditional use as a sacrament in the orally active preparation of ayahuasca. Although the religious use of ayahuasca has been examined extensively, very little is known about the recreational use of DMT. In this study, Australian participants (n=121) reporting at least one lifetime use of DMT completed an online questionnaire recording patterns of use, subjective effects and attitudes towards their DMT use. Smoking DMT was by far the most common route of administration (98.3%) with a comparatively smaller proportion reporting use of ayahuasca (30.6%). The reasons for first trying DMT were out of a general interest in hallucinogenic drugs (46.6%) or curiosity about DMT's effects (41.7%), while almost one-third (31.1%) cited possible psychotherapeutic benefits of the drug. An increase in psychospiritual insight was the most commonly reported positive effect of both smoked DMT (75.5%) and ayahuasca (46.7%), a finding that is consistent with other studies examining the ritualised use of ayahuasca in a religious context. Although previous studies of DMT use have examined ayahuasca use exclusively, the present study demonstrates the ubiquity of smoking as the most prevalent route of administration among recreational DMT users. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

The drug-use patterns of helping-profession students in Brisbane, Australia.

PubMed

Engs, R C

1980-10-01

A survey of 1691 first-and final-year students in the helping professions (medicine, law, nursing, pharmacy, police science, seminary, social work/ psychology, and teaching) as to their use of drugs was carried out during February to April, 1980, in Brisbane, Australia. The results indicated that about 86% drank coffee or tea, 85% drank alcohol, 85% used non-prescription analgesics, 31% used tobacco, 25% antihistamines, 9% marijuana, 9% sedatives, 6% tranquilizers, 2% hallucinogens, 2% stimulants, 1% cocaine and 1% used opiates at least once a year. Of these students, females used analgesics and antihistamines significantly more frequently than males and consumed more caffeine, tobacco and analgesics than males, while males drank significantly more alcohol than females. Final-year students used more alcohol, coffee or tea and tobacco, and used marijuana, coffee and tea and tobacco significantly more frequently than first-year students. Individuals who did not consider religion important used more alcohol and tobacco and used marijuana, tobacco and hallucinogens more frequently compared to individuals who considered religion to be important. There was also a significant difference in drug usage between the different courses of study for most of the substances, with law students using the majority of substances the most frequently and seminarians the least frequently.

Substance Use and Mental Health Trends among U.S. Military Active Duty Personnel: Key Findings from the 2008 DoD Health Behavior Survey

DTIC Science & Technology

2010-06-01

marijuana or hashish, cocaine. LSD, PCP. MDMA , other hallucino- gens, methamphetamine, heroin, GHB/GBL, and inhalants. Prescription drugs included...dayB. Any Illinit Dmg LJsp inRluning Prèsf.nptinn Drug K îsiLsa = »sa nt manjuana cocaine (including crackl, hallucinogens (PCP WDA MDMA and othet...S. bartnlurates/sedaiivas. orpain wlievers Illiril nn [Isp. F^i:lnili = use o( marijuana, cocaine ¡including Crack), hallucinpgens (PCP. MDA, MDMA

Psilocybin in Finnish Psilocybe semilanceata.

PubMed

Jokiranta, J; Mustola, S; Ohenoja, E; Airaksinen, M M

1984-06-01

The use of a hallucinogenic mushroom, PSILOCYBE SEMILANCEATA, has been occasionally reported in Finland, where the species is widely distributed. We have determined, by HPLC, the content of psilocybin and psilocin in P. SEMILANCEATA samples collected from different parts of Finland; the psilocybin content was found to be high (0.62-2.37%, mean 1.42% of dry weight), some samples also contained low concentrations (0.01-0.02% dry weight) of psilocin.

An Exploratory Analysis of Misconduct Behavior within the Radioman Rate and Its Potential Effect on Security

DTIC Science & Technology

1986-06-01

substance with the intent to distribute. "a’ Hallucinoena/ Psychedelics . A group of diverse, heterogeneus compounds all with the ability to induce !2ual...cognition and perception. Most common categories are: LSD! mescaline and peyote: "*" psilocybin: and psychedelic amphetamine variants (STP, MDA). Although a...drums. 4. I have used stimulant, depressant. or hallucinogens/ psychedelics drums over one year ago. S. I have been convicted of a drug abuse offense. 6

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

PubMed

Moreno, Francisco A; Wiegand, Christopher B; Taitano, E Keolani; Delgado, Pedro L

2006-11-01

Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p

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

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.

PubMed

Johnson, Matthew W; Garcia-Romeu, Albert; Cosimano, Mary P; Griffiths, Roland R

2014-11-01

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction. © The Author(s) 2014.

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

PubMed

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

1999-06-01

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

The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats.

PubMed

Commissaris, R; Lyness, W H; Cordon, J J; Moore, K E; Rech, R H

1980-11-01

The purpose of the present study was to determine the role of central catecholaminergic neuronal systems in the effects of LSD, DOM and d-amphetamine on fixed ratio (FR) operant responding in rats. Food-deprived male rats were trained to press a bar for food reinforcement on a FR-40 schedule. Control responding on this schedule is characterized by a rapid, constant rate of responding (approximately 100 responses/min) throughout a 40 min test session. LSD and DOM, as with other hallucinogens, produced dose-dependent periods of nonresponding or "pausing," followed by reinstatement of responding at or near the control rate. Administration of the non-hallucinogen, d-amphetamine, did not produce "pausing," but caused the response rate to slow and become erratic. In animals pretreated intraventricularly with 6-hydroxydopamine (6-OHDA; 200 micrograms/10 microliter X 2), the response to LSD and DOM was unchanged, while the response to d-amphetamine was significantly diminished. The neurotoxin significantly decreased brain catecholamines to less than 25 percent of control in al regions examined, without altering 5-HT concentrations in these same regions. These data demonstrate that the effects of LSD and DOM on FR-40 responding are quite different from those of d-amphetamine, and that this difference may be due to the extent of catecholamine involvement in the effects of these agents.

Characterization of behavioral and endocrine effects of LSD on zebrafish.

PubMed

Grossman, Leah; Utterback, Eli; Stewart, Adam; Gaikwad, Siddharth; Chung, Kyung Min; Suciu, Christopher; Wong, Keith; Elegante, Marco; Elkhayat, Salem; Tan, Julia; Gilder, Thomas; Wu, Nadine; Dileo, John; Cachat, Jonathan; Kalueff, Allan V

2010-12-25

Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Straightforward single-calibrant quantification of seized designer drugs by liquid chromatography-chemiluminescence nitrogen detection.

PubMed

Rasanen, Ilpo; Kyber, Marianne; Szilvay, Ilmari; Rintatalo, Janne; Ojanperä, Ilkka

2014-04-01

Sixty-one different psychoactive substances were quantified by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND) in 177 samples, using a single secondary standard (caffeine), in a trial concerning the quantitative purity assessment of drug-related material seized by the police in 2011-2012 and customs in 2011-2013 in Finland. The substances found were predominantly substituted phenethylamines, cathinones, tryptamines and synthetic cannabinoids, which were identified by appropriate methods prior to submitting the samples for quantification by LC-CLND. The equimolarity and expanded uncertainty of measurement by LC-CLND were on average 95% and 13%, respectively, based on 16 different substances. The median (mean) purity of stimulant/hallucinogenic drug samples seized at the border was 92.9% (87.6%) and in the street 82.0% (64.5%). The corresponding figures for powdery synthetic cannabinoid samples seized at the border and in the street were 99.0% (96.8%) and 90.0% (92.2%), respectively. There was generally only one active drug to be quantified in each sample. Seized herbal samples contained 0.15-9.2% of between one and three components. LC-CLND was found to be suitable for quantification of the nitrogen-containing drugs encountered in the study, showing sufficient N-equimolarity for both stimulant/hallucinogenic drugs and synthetic cannabinoids. The technique possesses great potential as a standard technique in forensic laboratories. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effects and consequences of selected club drugs.

PubMed

Freese, Thomas E; Miotto, Karen; Reback, Cathy J

2002-09-01

Ecstasy (MDMA), gamma-hydroxybutyrate (GHB), ketamine, and methamphetamine are 4 examples of club drugs that are increasing in popularity. Although the pharmacological classifications of these drugs vary, MDMA has structural similarities to both amphetamine and the hallucinogen mescaline. Ketamine and GHB are anesthetic agents and methamphetamine is a long-acting psychostimulant. Medical visits for club drug-related toxicity have sharply increased across the country. This article provides a brief review of the literature on club drugs. Copyright 2002 Elsevier Science Inc.

Seeing and thinking: Foundational issues and empirical horizons.

PubMed

Firestone, Chaz; Scholl, Brian J

2016-01-01

The spectacularly varied responses to our target article raised big-picture questions about the nature of seeing and thinking, nitty-gritty experimental design details, and everything in between. We grapple with these issues, including the ready falsifiability of our view, neuroscientific theories that allow everything but demand nothing, cases where seeing and thinking conflict, mental imagery, the free press, an El Greco fallacy fallacy, hallucinogenic drugs, blue bananas, subatomic particles, Boeing 787s, and the racial identities of geometric shapes.

5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism.

PubMed

Leth-Petersen, Sebastian; Petersen, Ida N; Jensen, Anders A; Bundgaard, Christoffer; Bæk, Mathias; Kehler, Jan; Kristensen, Jesper L

2016-11-16

The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT 2A /5-HT 2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT 2 receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans.

PubMed

Carter, Olivia L; Hasler, Felix; Pettigrew, John D; Wallis, Guy M; Liu, Guang B; Vollenweider, Franz X

2007-12-01

Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis. The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation. This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 microg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects. Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin's "positive" psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug's "negative-type symptoms" associated with reduced arousal and vigilance. Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin's effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

The role of serotonin 5-HT2A receptors in memory and cognition

PubMed Central

Zhang, Gongliang; Stackman, Robert W.

2015-01-01

Serotonin 5-HT2A receptors (5-HT2ARs) are widely distributed in the central nervous system, especially in brain region essential for learning and cognition. In addition to endogenous 5-HT, several hallucinogens, antipsychotics, and antidepressants function by targeting 5-HT2ARs. Preclinical studies show that 5-HT2AR antagonists have antipsychotic and antidepressant properties, whereas agonist ligands possess cognition-enhancing and hallucinogenic properties. Abnormal 5-HT2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia, and drug addiction. In addition to its traditional activity as a G protein-coupled receptor (GPCR), recent studies have defined novel operations of 5-HT2ARs. Here we review progress in the (1) receptor anatomy and biology: distribution, signaling, polymerization and allosteric modulation; and (2) receptor functions: learning and memory, hallucination and spatial cognition, and mental disorders. Based on the recent progress in basic research on the 5-HT2AR, it appears that post-training 5-HT2AR activation enhances non-spatial memory consolidation, while pre-training 5-HT2AR activation facilitates fear extinction. Further, the potential influence that 5-HT2AR-elicited visual hallucinations may have on visual cue (i.e., landmark) guided spatial cognition is discussed. We conclude that the development of selective 5-HT2AR modulators to target distinct signaling pathways and neural circuits represents a new possibility for treating emotional, neuropsychiatric, and neurodegenerative disorders. PMID:26500553

Opaque models: Using drugs and dreams to explore the neurobiological basis of mental phenomena.

PubMed

Langlitz, Nicolas

2017-01-01

On the basis of four historical and ethnographic case studies of modeling in neuroscience laboratories, this chapter introduces a distinction between transparent and opaque models. A transparent model is a simplified representation of a real world phenomenon. If it is not patently clear, it is at least much better comprehended than its objects of representation. An opaque model, by contrast, looks at one only partially understood phenomenon to stand in for another partially understood phenomenon. Here, the model is often just as complex as its target. Examples of such opaque models discussed in this chapter are the use of hallucinogen intoxication in humans and animals as well as the dreaming brain as models of psychosis as well as the dreaming brain as a model of consciousness in general. Several functions of opaque models are discussed, ranging from the generation of funding to the formulation of new research questions. While science studies scholars have often emphasized the epistemic fertility of failures of representation, the opacity of hallucinogen intoxications and dreams seems to have diminished the potential to produce positive knowledge from the representational relationship between the supposed models and their targets. Bidirectional comparisons between inebriation, dreaming, and psychosis, however, proved to be generative on the level of basic science. Moreover, the opaque models discussed in this chapter implicated cosmologies that steered research endeavors into certain directions rather than others. © 2017 Elsevier B.V. All rights reserved.

Disruption of Prefrontal Cortex Large Scale Neuronal Activity by Different Classes of Psychotomimetic Drugs

PubMed Central

Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2012-01-01

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spikerate and LFP power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease. PMID:22378875

The 5-HT1A Receptor and the Stimulus Effects of LSD in the Rat

PubMed Central

Reissig, C.J.; Eckler, J.R.; Rabin, R.A.; Winter, J.C.

2005-01-01

Rationale It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). Objectives The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Methods 12 Male F-344 rats were trained in a two-lever, fixed ratio10, food reinforced task with LSD (0.1 mg/kg; IP; 15 min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT1A agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg; SC; 30 min. pretreatment). Results In combination tests stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. Conclusions These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD. PMID:16025319

Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product.

PubMed

Lenz, Claudius; Wick, Jonas; Hoffmeister, Dirk

2017-10-27

We report the identification of ω-N-methyl-4-hydroxytryptamine (norpsilocin, 1) from the carpophores of the hallucinogenic mushroom Psilocybe cubensis. The structure was elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin has not previously been reported as a natural product. It likely represents the actual psychotropic agent liberated from its 4-phosphate ester derivative, the known natural product baeocystin. We further present a simple and artifact-free extraction method that prevents dephosphorylation and therefore helps reflect the naturally occurring metabolic profile of Psilocybe mushrooms in subsequent analyses.

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.

Legally high? Legal considerations of Salvia divinorum.

PubMed

Griffin, O Hayden; Miller, Bryan Lee; Khey, David N

2008-06-01

The legal status of the hallucinogenic plant Salvia divinorum has been rapidly changing. Legal prohibitions on this plant native to Oaxaca, Mexico have emerged at the state level, a phenomenon that has not occurred since the passage of the Controlled Substances Act (CSA). Included will be a brief description of the plant that has only recently crept into the popular American consciousness, and a review of the different legal mechanisms through which states have controlled the plant and the pending legislation proposing controls. Lastly, the implications of various state laws are discussed.

Poisoning by hallucinogenic mushroom hikageshibiretake (Psilocybe argentipes K. Yokoyama) indigenous to Japan.

PubMed

Musha, M; Ishii, A; Tanaka, F; Kusano, G

1986-01-01

Five cases of poisoning by indigenous mushroom Hikageshibiretake (Psilocybe argentipes) are reported. As this mushroom contains psilocybin, in general, clinical features were similar to those seen by pure psilocybin. Acute toxic stuporous state with complete amnesia in the culminating period occurred in one case, psychedelic state with dreamy consciousness in one case and psychotic adverse reactions with vivid visual hallucinations with consciousness in three cases. There were accompanied with anxiety and panic reactions to subjective experiences. Though these toxic effects were usually short-lived, for management of such patients it is important to recognize that horrible emotional reactions and other harmful behavioral problems can also occur.

Patterns of drug use and HIV infection among adults in a nationally representative sample

PubMed Central

Shiau, Stephanie; Arpadi, Stephen M.; Yin, Michael T.; Martins, Silvia S.

2017-01-01

Background Little is known about drug use patterns among people living with HIV in comparison to an uninfected group in the general population. The aim of this study was to investigate the association between legal and illegal drug use and HIV infection in a nationally representative sample of adults in the United States. Methods Public use data files (2005–2014) from the National Survey on Drug Use and Health (NSDUH) were used. Respondents were asked whether a medical professional had ever told them that they had HIV/AIDS. Ever (lifetime), past-year, and past month use of cigarettes, alcohol, marijuana, cocaine, heroin, hallucinogens, inhalants, and nonmedical use of psychotherapeutics was assessed. Logistic regression was used to estimate adjusted odds ratios (aOR) of the relationship between drug use and HIV infection, adjusting for demographics. Results Of 377,787 respondents age 18 and older, 548 (0.19%) were categorized as HIV-infected. Ever use of cigarettes, tobacco, marijuana, cocaine, heroin, hallucinogens, inhalants, and psychotherapeutics was higher in HIV-infected individuals compared to HIV-uninfected individuals after adjustment for sex, age, race/ethnicity, education, total family income, and marital status. Past year and past month use was also higher for HIV-infected individuals for all substances aside from alcohol. Conclusions In a nationally representative sample, there are higher levels of drug use and DSM-IV dependence among the HIV-infected population compared to the HIV-uninfected population. This is of concern because drug use and dependence can impede engagement in HIV care and adherence to antiretroviral therapy. PMID:28088742

The phenomenology of the psychotic break and Huxley's trip: substance use and the onset of psychosis.

PubMed

Nelson, Barnaby; Sass, Louis A

2008-01-01

While considerable research attention has been devoted to the causal relationship between substance use and psychosis, the phenomenology of the association between the two has largely been ignored. This is a significant shortcoming, because it blinds researchers to the possibility that there may be elements of the subjective experience of substance use and psychosis that contribute to their apparent relationship in empirical studies. The current paper examines the phenomenology of the onset of psychosis and the phenomenology of substance intoxication through consideration of two texts: Sass's account of the phenomenology of psychosis onset and Huxley's account of the experience of hallucinogenic intoxication. Sass's account of psychosis onset includes four components: Unreality, Fragmentation, Mere Being, and Apophany. The analysis reveals significant parallels - and also some differences - between this account and the phenomenology of substance intoxication. We discuss the implications of this for the causal relationship between psychosis and substance use and suggest several ways of understanding the overlapping phenomenologies. This includes the suggestion of a shared factor, perhaps best described as psychotic-like experience, which seems to involve a breakdown of the sign-referent relationship and relationship with the common-sense, practical world. However, in the onset of psychosis, this breakdown is primarily experienced as a sense of alienation from self and world, whereas in the hallucinogenic state a sense of mystical union and revelation seems predominant. Further research may extend this analysis by looking at experiences with other drugs, particularly cannabis, and by examining the phenomenology of psychotic disorder beyond the first episode. (c) 2008 S. Karger AG, Basel.

Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro.

PubMed

Giacomelli, S; Palmery, M; Romanelli, L; Cheng, C Y; Silvestrini, B

1998-01-01

The hallucinogenic effects of lysergic acid diethylamide (LSD) have mainly been attributed to the interaction of this drug with the serotoninergic system, but it seems more likely that they are the result of the complex interactions of the drug with both the serotoninergic and dopaminergic systems. The aim of the present study was to investigate the functional actions of LSD at dopaminergic receptors using prolactin secretion by primary cultures of rat pituitary cells as a model. LSD produced a dose-dependent inhibition of prolactin secretion in vitro with an IC50 at 1.7x10(-9) M. This action was antagonized by spiperone but not by SKF83566 or cyproheptadine, which indicates that LSD has a specific effect on D2 dopaminergic receptors. The maximum inhibition of prolactin secretion achieved by LSD was lower than that by dopamine (60% versus 80%). Moreover, the fact that LSD at 10(-8)-10(-6) M antagonized the inhibitory effect of dopamine (10(-7) M) and bromocriptine (10(-11) M) suggests that LSD acts as a partial agonist at D2 receptors on lactotrophs in vitro. Interestingly, LSD at 10(-13)-10(-10) M, the concentrations which are 10-1000-fold lower than those required to induce direct inhibition on pituitary prolactin secretion, potentiated the dopamine (10(-10)-2.5x10(-9) M)-mediated prolactin secretion by pituitary cells in vitro. These results suggest that LSD not only interacts with dopaminergic receptors but also has a unique capacity for modulating dopaminergic transmission. These findings may offer new insights into the hallucinogenic effect of LSD.

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.

PubMed

Dawson, Patrick; Opacka-Juffry, Jolanta; Moffatt, James D; Daniju, Yusuf; Dutta, Neelakshi; Ramsey, John; Davidson, Colin

2014-01-03

5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in 'head shops' and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB's activity at the 5-HT2B receptor may cause cardiotoxicity. © 2013.

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

PubMed

Zghoul, Tarek; Blier, Pierre

2003-03-01

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

The role of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to test blood and urine samples for the toxicological investigation of drug-facilitated crimes.

PubMed

Deveaux, Marc; Chèze, Marjorie; Pépin, Gilbert

2008-04-01

The authors present an overview of the drug-facilitated crime (DFC) phenomenon, especially in France. Recently, there has been an increase in reports of incidents (mainly sexual assaults and robbery) as well as in scientific publications and congress presentations on the topic. From enquiries conducted nationally, a list of drugs reportedly associated with DFC was established and includes benzodiazepines and benzodiazepine-like drugs (zolpidem, zopiclone), minor tranquilizers and neuroleptics, barbiturates, narcotics, hallucinogens, and anaesthetics. Some of these molecules are specific to France in DFC cases. A study using healthy volunteers who had taken benzodiazepines (lorazepam, bromazepam, flunitrazepam, clonazepam), zolpidem and zopiclone, showed that the only way to increase the duration of detection of these drugs is to use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to test blood and urine samples. The very high sensitivity of this method appears to be an essential condition to document the cases, because the drugs tested were still detectable in urine at least 6 days after the ingestion of one therapeutic dose. Limits of detection were always lower than 0.5 ng/mL in urine. The actual list of molecules and metabolites the authors screened for in urine and blood by LC-MS/MS, in every DFC, is given in detail: 25 benzodiazepines and benzodiazepine-like drugs, 11 minor tranquilizers and neuroleptics, 2 barbiturates, 12 narcotics, 4 hallucinogens, and 1 anaesthetic. However, the distinction between continual therapeutic use of a psychotropic drug or illegal narcotic and a single ingestion has to be documented by sequential analysis of hair, again with LC-MS/MS.

The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.

PubMed

Tancer, Manuel; Johanson, Chris-Ellyn

2007-01-01

The purpose of this study was to investigate the role of serotonin (5-HT) in the effects of oral 3,4-methylenedioxymethamphetamine (MDMA) in humans. The subjective and physiological effects of 1.5 mg/kg MDMA were evaluated after 20 mg fluoxetine in eight recreational MDMA users in a double-blind, placebo-controlled study. During phase 1, participants were maintained on placebo for at least 5 days and tested with MDMA and placebo on separate sessions. In phase 2, the procedure was the same except fluoxetine was administered daily for at least 5 days. During sessions, placebo or fluoxetine was given 1 h before the session drug and effects were measured over the next 7 h. MDMA increased positive-like subjective effects on all the Addiction Research Center Inventory scales; Arousal, Elation, Positive Mood, and Vigor on the Profile of Mood States; Drug Liking, Friendly, Good Drug Effect, High, Stimulated, and Talkative on the Visual Analog Scale; and End-of-Session Liking and Crossover Point on the Multiple Choice Procedure. MDMA also increased measures of anxiety. On the Hallucinogenic Rating Scale, all scales except Volition were increased. MDMA also increased blood pressure and heart rate. Fluoxetine treatment attenuated most of the positive-like subjective effects including the Affect and Soma scales of the Hallucinogen Rating Scale. In addition, heart rate but not blood pressure increases were reduced. These results suggest that blockade of 5-HT reuptake by fluoxetine can dampen the effects of MDMA and further supports the role of 5-HT in its behavioral effects in humans.

Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans

PubMed Central

Ranganathan, Mohini; Schnakenberg, Ashley; Skosnik, Patrick D.; Cohen, Bruce; Pittman, Brian; Sewell, R. Andrew; D’Souza, Deepak Cyril

2012-01-01

Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA), a highly selective agonist at the kappa opiate receptor (KOR), is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological and endocrine effects of 0 mg, 8 mg and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power. SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits or changes in vital signs. The effects were transient and not dose-related. SA administration was very well tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with KOR agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved and to explore the basis for individual variability in its effects. PMID:22817868

Epidemiology of adolescent Salvia divinorum use in Canada.

PubMed

Currie, Cheryl L

2013-02-01

Salvia divinorum is a potent, naturally occurring hallucinogen gaining popularity as a recreational drug in North America. To date, detailed epidemiologic information about the use of this substance among adolescents living outside the United States has been limited. This study provides information on the prevalence and correlates of Salvia divinorum use among adolesecents in Canada using a nationally representative sample. Data were obtained from a representative sample of 42,179 Canadian adolescents aged 12-17 years living across all 10 provinces who completed the Youth Smoking Survey in 2008-09. Overall, 3.8% of adolescents reported using Salvia in the past year and 6.2% had used the substance in their lifetime. A conservative estimate suggests 23.2% of youth were repeat users. Salvia use was highest among youth in British Columbia and Quebec. Comparatively, the prevalence of 12-month Salvia use was higher than 12-month cocaine and amphetamine use but lower than 12-month ecstasy, cannabis, and other hallucinogen use. Correlates of Salvia use included older age, male gender, high available spending money, binge drinking, illicit drug use and smoking in fully adjusted models. Findings suggest low self-esteem may be an important correlate specific to the use of this substance among youth. Salvia divinorum use is prevalent among Canadian adolescents. Salvia may be a significant public health issue in Canada given it is readily available, under limited regulation, and little is known about the abuse liability of the substance, interactions with other substances, and potential complications from use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Forbidden therapies: Santo Daime, ayahuasca, and the prohibition of entheogens in Western society.

PubMed

Blainey, Marc G

2015-02-01

Santo Daime, a Brazilian religion organized around a potent psychoactive beverage called ayahuasca, is now being practiced across Europe and North America. Deeming ayahuasca a dangerous "hallucinogen," most Western governments prosecute people who participate in Santo Daime. On the contrary, members of Santo Daime (called "daimistas") consider ayahuasca a medicinal sacrament (or "entheogen"). Empirical studies corroborate daimistas' claim that entheogens are benign and can be beneficial when employed in controlled contexts. Following from anthropology's goal of rendering different cultural logics as mutually explicable, this article intercedes in a misunderstanding between policies of prohibition and an emergent subculture of entheogenic therapy.

Non-medical drug use behaviour at five United States universities: a 15-year study.

PubMed

Dezelsky, T L; Toohey, J V; Shaw, R S

1985-01-01

A survey carried out in 1970, 1973, 1976, 1980 and 1984 by means of a questionnaire at five American universities, which involved a total of 4,171 students, showed an increase in the use of cocaine, cannabis, hallucinogens, sedatives, amphetamines and alcohol. Cocaine use increased from 2.7 per cent in 1970 to 30 per cent in 1984, while cannabis use almost doubled during that period. The survey found that intercollegiate athletes used significantly more anabolic steroids than non-athletes, but with regard to the use of other substances the athletic students did not differ significantly from non-athletic students.

Psychedelics and Personality.

PubMed

Aixalà, Marc; Dos Santos, Rafael G; Hallak, Jaime E C; Bouso, José Carlos

2018-06-04

In the past decade, an increasing number of clinical trials are reporting evidence that psychedelics or serotonergic hallucinogens (such as lysergic acid diethylamide, psilocybin, and ayahuasca/dimethyltryptamine) could be effective in the treatment of mood, anxiety, and substance use disorders. The mechanisms responsible for these effects are not fully understood but seem to involve changes in bran dynamics in areas rich in serotonergic 5-HT 2A receptors and in personality. In the present text, we present a brief and critical overview of the current research in this field, pointing out both promises and limitations of these studies.

Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats.

PubMed

da Motta, Luciana Gueiros; de Morais, Juliana Alves; Tavares, Ana Carolina A M; Vianna, Leonora Maciel Sousa; Mortari, Marcia Renata; Amorim, Rivadávio Fernandes Batista; Carvalho, Rosângela R; Paumgartten, Francisco José R; Pic-Taylor, Aline; Caldas, Eloisa Dutra

2018-04-01

Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose. At non-lethal doses, AYA enhanced embryolethality and the incidence of foetal soft-tissue and skeleton anomalies. This study suggested that AYA is developmentally toxic and that its daily use by pregnant women may pose risks for the conceptus. Copyright © 2018 Elsevier Inc. All rights reserved.

Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A†

PubMed Central

Lozama, Anthony; Cunningham, Christopher W.; Caspers, Michael J.; Douglas, Justin T.; Dersch, Christina M.; Rothman, Richard B.; Prisinzano, Thomas E.

2011-01-01

As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan containing natural products. PMID:21338114

Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.

PubMed

Lozama, Anthony; Cunningham, Christopher W; Caspers, Michael J; Douglas, Justin T; Dersch, Christina M; Rothman, Richard B; Prisinzano, Thomas E

2011-04-25

As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products.

Amphetamines, Barbiturates and Hallucinogens; An Analysis of Use, Distribution, and Control. Final Report.

ERIC Educational Resources Information Center

McGlothlin, William H.

This report is the third of three monographs to provide perspectives on the use, distribution, and control of illicit drugs. The first, conducted in 1971, described the prevalence, use patterns, sources, distribution, and economics of the marihuana market. The second (1972) estimated the cost, benefits, and potential of approaches to narcotic…

MDA, MDMA, and other "mescaline-like" substances in the US military's search for a truth drug (1940s to 1960s).

PubMed

Passie, Torsten; Benzenhöfer, Udo

2018-01-01

This article describes the context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes from the 1940s to the 1960s. Germans first tested mescaline as a "truth drug" in a military context. In the 1940s, the United States military started testing hallucinogenic substances as truth drugs for interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible "speech-inducing" effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the compounds delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/1954 revealed that some of the "mescaline derivatives" tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. In 1955, the military changed focus to lysergic acid diethylamide (LSD), but some interest in mescaline-like compounds remained for their ability to change mood and habit without interfering with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) whether any of the mescaline derivatives tested were being used operationally. Copyright © 2017 John Wiley & Sons, Ltd.

Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

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

Ebersole, B.L.J.

The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies ofmore » brain areas from mice that received injections of (/sup 3/H)LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free (/sup 3/H)LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.« less

Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia

PubMed Central

Malkova, Natalia V.; Gallagher, Joseph J.; Yu, Collin Z.; Jacobs, Russell E.; Patterson, Paul H.

2014-01-01

Maternal infection during pregnancy increases the risk for schizophrenia in offspring. In rodent models, maternal immune activation (MIA) yields offspring with schizophrenia-like behaviors. None of these behaviors are, however, specific to schizophrenia. The presence of hallucinations is a key diagnostic symptom of schizophrenia. In mice, this symptom can be defined as brain activation in the absence of external stimuli, which can be mimicked by administration of hallucinogens. We find that, compared with controls, adult MIA offspring display an increased stereotypical behavioral response to the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), an agonist for serotonin receptor 2A (5-HT2AR). This may be explained by increased levels of 5-HT2AR and downstream signaling molecules in unstimulated MIA prefrontal cortex (PFC). Using manganese-enhanced magnetic resonance imaging to identify neuronal activation elicited by DOI administration, we find that, compared with controls, MIA offspring exhibit a greater manganese (Mn2+) accumulation in several brain areas, including the PFC, thalamus, and striatum. The parafascicular thalamic nucleus, which plays the role in the pathogenesis of hallucinations, is activated by DOI in MIA offspring only. Additionally, compared with controls, MIA offspring demonstrate higher DOI-induced expression of early growth response protein 1, cyclooxygenase-2, and brain-derived neurotrophic factor in the PFC. Chronic treatment with the 5-HT2AR antagonist ketanserin reduces DOI-induced head twitching in MIA offspring. Thus, the MIA mouse model can be successfully used to investigate activity induced by DOI in awake, behaving mice. Moreover, manganese-enhanced magnetic resonance imaging is a useful, noninvasive method for accurately measuring this type of activity. PMID:24889602

Psychoactive substances, alcohol and tobacco consumption in HIV-infected outpatients.

PubMed

Jacquet, Jean-Marc; Peyriere, Hélène; Makinson, Alain; Peries, Marianne; Nagot, Nicolas; Donnadieu-Rigole, Hélène; Reynes, Jacques

2018-06-01

To assess the alcohol consumption, tobacco addiction and psychoactive substance use (PSU) of people living with HIV (PLHIV). Cross-sectional study in an HIV outpatient unit. Autoquestionnaire systematically proposed to all patients during their usual clinical care visit during a 6-months period, for alcohol (AUDIT test), tobacco (Short Fagerstrom Test) and PSU (ASSIST V3.0 test). Of 1334 distributed questionnaires, 1018 PLHIV responded: 76.8% were men [528 patients were MSM), and the median age was 49 years (interquartile range: 42-46). A prevalence of excessive alcohol drinking was found in 22% [95% confidence interval (CI) 19.5-24.7%] and 44.6% (CI 41.5-47.7%) were current smokers, with high dependence in 29.1% (CI 24.9-33.7%). The prevalence of PSU was 37.8% (CI 34.8-41%) in the past 3 months: cannabis 27.7%, poppers 16.4%, cocaine 8.9%, psychotropic medications 7.1%, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) 4.7%, stimulants 3.1%, synthetic cathinones 2.7%, hallucinogens 1.5%. In the past 3 months, PSU was more prevalent in MSM than in non-MSM patients (46 versus 30%, P < 0.001). MSM consumed significantly more inhaled solvents (poppers) 31.0 versus 1.1%, GHB/GBL 7.8 versus 0.8%, stimulants 5.0 versus 1.1%, synthetic cathinones 4.9 versus 0.3%, and hallucinogens 2.3 versus 0.5%. Given the high prevalence of PSU and other addictions (alcohol and smoking) among PLHIV, and particularly among MSM, a systematic screening of PSU and other addictions should be part of routine clinical care.

Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia.

PubMed

Malkova, Natalia V; Gallagher, Joseph J; Yu, Collin Z; Jacobs, Russell E; Patterson, Paul H

2014-06-17

Maternal infection during pregnancy increases the risk for schizophrenia in offspring. In rodent models, maternal immune activation (MIA) yields offspring with schizophrenia-like behaviors. None of these behaviors are, however, specific to schizophrenia. The presence of hallucinations is a key diagnostic symptom of schizophrenia. In mice, this symptom can be defined as brain activation in the absence of external stimuli, which can be mimicked by administration of hallucinogens. We find that, compared with controls, adult MIA offspring display an increased stereotypical behavioral response to the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), an agonist for serotonin receptor 2A (5-HT2AR). This may be explained by increased levels of 5-HT2AR and downstream signaling molecules in unstimulated MIA prefrontal cortex (PFC). Using manganese-enhanced magnetic resonance imaging to identify neuronal activation elicited by DOI administration, we find that, compared with controls, MIA offspring exhibit a greater manganese (Mn(2+)) accumulation in several brain areas, including the PFC, thalamus, and striatum. The parafascicular thalamic nucleus, which plays the role in the pathogenesis of hallucinations, is activated by DOI in MIA offspring only. Additionally, compared with controls, MIA offspring demonstrate higher DOI-induced expression of early growth response protein 1, cyclooxygenase-2, and brain-derived neurotrophic factor in the PFC. Chronic treatment with the 5-HT2AR antagonist ketanserin reduces DOI-induced head twitching in MIA offspring. Thus, the MIA mouse model can be successfully used to investigate activity induced by DOI in awake, behaving mice. Moreover, manganese-enhanced magnetic resonance imaging is a useful, noninvasive method for accurately measuring this type of activity.

Phencyclidine and Chemical “Stroking”

PubMed Central

Alexander, Ranya L.

1980-01-01

The current wave of drug abuse is but the latest manifestation of the real human need for “stroking.” Drugs which affect the pleasure center of the brain are prime objects of abuse. Phencyclidine (“PCP” or “angel dust”) is a cyclohexylamine which has properties of the amphetamine-stimulants, the narcotic-depressants and the hallucinogens. Previously unrecognized population groups include children less than six years of age and pregnant women and their intoxicated offspring. Successful treatment of present and future patients must be multidisciplinary and will ultimately depend upon a clear understanding of the pharmacology, social psychology, politics, and economics of drugs of abuse. PMID:7191444

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

PubMed

Grob, Charles S; Danforth, Alicia L; Chopra, Gurpreet S; Hagerty, Marycie; McKay, Charles R; Halberstadt, Adam L; Greer, George R

2011-01-01

Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. A clinical research unit within a large public sector academic medical center. Twelve adults with advanced-stage cancer and anxiety. In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. clinicaltrials.gov Identifier: NCT00302744.

Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.

PubMed

Kometer, Michael; Schmidt, André; Jäncke, Lutz; Vollenweider, Franz X

2013-06-19

Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.

Driving under the influence of drugs: Perceptions and attitudes of New Zealand drivers.

PubMed

Malhotra, Neha; Starkey, Nicola J; Charlton, Samuel G

2017-09-01

This study explored the patterns of drug driving in New Zealand by investigating 1) drivers' perceptions about impairment caused by legal and illegal drugs 2) countermeasures employed by drivers when under the influence of drugs (e.g., decisions not to drive) 3) drivers' attitudes about police enforcement of drug driving and 4) the factors that predict the likelihood of engaging in drug driving. Participants (n=434) were licensed drivers who completed an online questionnaire. Results of the questionnaire indicated that drivers rated hallucinogens and opiates as being the illegal drugs producing the highest level of driving impairment and cannabis the lowest. For legal drugs, sedatives were rated as having the highest driving impairment and anti-nausea and anti-depressants the lowest. Respondents' drug use history had an effect on their ratings of impairment for anti-anxiety drugs, anti-depressants, kava, sedatives, cannabis and hallucinogens such that drug users reported higher impairment ratings than Non-user. Making a decision not to drive after taking drugs was reported by users of alcohol (73.6%), cannabis (57.0%), strong painkillers (42.5%), and anti-depressants (10.0%). Respondents who reported drink driving were 3.26 times more likely to report drug driving than those reporting no drink driving. Respondents also showed greater acceptance towards driving under the influence of legal drugs (43.5%) compared to illegal drugs (10.3%). Those who did not have favourable attitudes about drug driving were less likely to report having driven under the influence of drugs. Drivers in this sample were less aware of the potential negative effects of legal drugs on driving compared to illegal drugs. More than half the respondents from this study acknowledged drug driving as a road safety issue which needs more resources dedicated to it. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

PubMed

McKenna, Dennis J

2004-05-01

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2

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

Perez-Aguilar, Jose Manuel; Shan, Jufang; LeVine, Michael V.

With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT 2AR) in the absence of ligand and bound to four distinct serotonergic agonists. Themore » 5-HT 2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT 2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT 2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. Lastly, the findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT 2AR activation.« less

A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2

DOE PAGES

Perez-Aguilar, Jose Manuel; Shan, Jufang; LeVine, Michael V.; ...

2014-10-14

With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT 2AR) in the absence of ligand and bound to four distinct serotonergic agonists. Themore » 5-HT 2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT 2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT 2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. Lastly, the findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT 2AR activation.« less

Return of the lysergamides. Part I: Analytical and behavioral characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

PubMed Central

Brandt, Simon D.; Kavanagh, Pierce V.; Westphal, Folker; Stratford, Alexander; Elliott, Simon P.; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L.

2015-01-01

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a ‘research chemical’ in form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic, mass spectrometric methods and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A-receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6J mice were injected with vehicle (saline) or 1P-LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, the HTR was abolished when 1P-LSD administration followed pre-treatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which confirms that the behavioral response is mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. PMID:26456305

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

PubMed

Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

2010-10-01

Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.

PubMed

Seeman, Philip; Guan, Hong-Chang; Hirbec, Hélène

2009-08-01

Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.

Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.

PubMed

Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

2005-06-01

The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

Case series: toxicity from 25B-NBOMe--a cluster of N-bomb cases.

PubMed

Gee, Paul; Schep, Leo J; Jensen, Berit P; Moore, Grant; Barrington, Stuart

2016-01-01

Background A new class of hallucinogens called NBOMes has emerged. This class includes analogues 25I-NBOMe, 25C-NBOMe and 25B-NBOMe. Case reports and judicial seizures indicate that 25I-NBOMe and 25C-NBOMe are more prevalently abused. There have been a few confirmed reports of 25B-NBOMe use or toxicity. Report Observational case series. This report describes a series of 10 patients who suffered adverse effects from 25B-NBOMe. Hallucinations and violent agitation predominate along with serotonergic/stimulant signs such as mydriasis, tachycardia, hypertension and hyperthermia. The majority (7/10) required sedation with benzodiazepines. Analytical method 25B-NBOMe concentrations in plasma and urine were quantified in all patients using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Peak plasma levels were measured between 0.7-10.1 ng/ml. Discussion The NBOMes are desired by users because of their hallucinogenic and stimulant effects. They are often sold as LSD or synthetic LSD. Reported cases of 25B- NBOMe toxicity are reviewed and compared to our series. Seizures and one pharmacological death have been described but neither were observed in our series. Based on our experience with cases of mild to moderate toxicity, we suggest that management should be supportive and focused on preventing further (self) harm. High doses of benzodiazepines may be required to control agitation. Patients who develop significant hyperthermia need to be actively managed. Conclusions Effects from 25B-NBOMe in our series were similar to previous individual case reports. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25C-NBOMe). Violent agitation frequently present along with signs of serotonergic stimulation. Hyperthermia, rhabdomyolysis and kidney injury were also observed.

Quantitative analysis of substituted N,N-dimethyl-tryptamines in the presence of natural type XII alkaloids.

PubMed

Ivanova, Bojidarka; Spiteller, Michael

2012-10-01

This paper reports the qualitative and quantitative analysis (QA) of mixtures of hallucinogens, N,N-dimethyltryptamine (DMT) (1), 5-methoxy- (la) and 5-hydroxy-N,N-dimethyltryptamine (1b) in the presence of beta-carbolines (indole alkaloids of type XII) ((2), (3) and (5)}. The validated electronic absorption spectroscopic (EAs) protocol achieved a concentration limit of detection (LOD) of 7.2.10(-7) mol/L {concentration limit of quantification (LOQ) of 24.10(-7) mol/L) using bands (lambda max within 260+/-0.23-262+/-0.33 nm. Metrology, including accuracy, measurement repeatability, measurement precision, trueness of measurement, and reproducibility of the measurements are presented using N,N-dimethyltryptamine (DMA) as standard. The analytical quantities of mixtures of alkaloids 4, 6 and 7 are: lambda max 317+/-0.45, 338+/-0.69 and 430+/-0.09 for 4 (LOD, 8.6.10(-7) mol/L; LOQ, 28.66(6), mol/L), as well as 528+/-0.75 nm for 6 and 7 (LOD, 8.2.10(-7) mol/L; LOQ, 27.33(3), mol/L), respectively. The partially validated protocols by high performance liquid chromatography (HPLC), electrospray ionization (ESI), mass spectrometry (MS), both in single and tandem operation (MS/MS) mode, as well as matrix/assisted laser desorption/ionization (MALDI) MS are elaborated. The Raman spectroscopic (RS) protocol for analysis of psychoactive substances, characterized by strong fluorescence RS profile was developed, with the detection limits being discussed. The known synergistic effect leading to increase the psychoactive and hallucinogenic properties and the reported acute poisoning cases from 1-7, make the present study emergent, since as well the current lack of analytical data and the herein metrology obtained contributed to the elaboration of highly selective and precise analytical protocols, which would be of interest in the field of criminal forensic analysis.

Use patterns and self-reported effects of Salvia divinorum: an internet-based survey.

PubMed

Baggott, Matthew J; Erowid, Earth; Erowid, Fire; Galloway, Gantt P; Mendelson, John

2010-10-01

There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD. To characterize the reasons, methods, and reported consequences of SD use. Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. Participants (N=500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1-250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drug's main effects were estimated to last 14.1 ± 12.8 (range 0.5-120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥ 24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety). SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Firearm carrying and concurrent substance use behaviours in a community-based sample of emerging adults.

PubMed

Buschmann, Robert N; Prochaska, John D; Baillargeon, Jacques G; Temple, Jeff R

2017-12-01

This paper examines associations between high-risk gun carrying and substance use in emerging adults (ages 18-22). The coexistence of these high-risk behaviours in a general population of emerging adults can have disastrous consequences. Dating it Safe is an ongoing longitudinal (2010-2016) survey of emerging adults recruited from seven high schools in five south-east Texas-area school districts (current sample n=684). Multiple logistic regression modelling was used to examine the association between past-year use of legal and illegal substances and past-year firearm carrying for a reason other than sport or hunting. 6% of emerging adults carried firearms in the past year, with most (68%) carrying for protection. Use of cocaine, hallucinogens, methamphetamine, ecstasy and prescription medications in the past year, as well as episodic heavy drinking in the past month, was associated with increased risk of carrying a firearm (p<0.05 for all). After controlling for covariates, hallucinogens (OR 2.81, 95% CI 1.00 to 7.81), ecstasy (OR 3.66, 95% CI 1.32 to 10.14) and prescription medications (OR 2.85, 95% CI 1.22 to 6.68) remained associated with firearm carrying. Episodic heavy drinking was associated with firearm carrying, but only for those who had five or more episodes/month (OR 3.61, 95% CI 1.51 to 8.66). In this community-based sample of emerging adults, firearm carrying, mostly for protection, was associated with a variety of past-year substance use behaviours. These findings extend previous research and suggest directions for further exploration of the clustering of high-risk behaviours in emerging adults. 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/.

Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

PubMed

Shah, N S; Gulati, O D

1984-01-01

Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

Immunological effects of ayahuasca in humans.

PubMed

dos Santos, Rafael Guimarães

2014-01-01

Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

Behavioral effects of MDMA ('ecstasy') on adult zebrafish.

PubMed

Stewart, Adam; Riehl, Russell; Wong, Keith; Green, Jeremy; Cosgrove, Jessica; Vollmer, Karoly; Kyzar, Evan; Hart, Peter; Allain, Alexander; Cachat, Jonathan; Gaikwad, Siddharth; Hook, Molly; Rhymes, Kate; Newman, Alan; Utterback, Eli; Chang, Katie; Kalueff, Allan V

2011-06-01

3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is a potent psychedelic drug inducing euphoria and hypersociability in humans, as well as hyperactivity and anxiety in rodents. Adult zebrafish (Danio rerio) have become a widely used species in neurobehavioral research. Here, we explore the effects of a wide range (0.25-120 mg/l) of acute MDMA doses on zebrafish behavior in the novel tank test. Although MDMA was inactive at lower doses (0.25-10 mg/l), higher doses reduced bottom swimming and immobility (40-120 mg/l) and impaired intrasession habituation (10-120 mg/l). MDMA also elevated brain c-fos expression, collectively confirming the usage of zebrafish models for screening of hallucinogenic compounds.

Substance use among medical students in Barcelona (Spain). A comparison with previous surveys.

PubMed

Rodriguez, M E; Cami, J

1986-11-01

During the academic year 1983-1984, a survey on drug consumption was conducted among medical students in Barcelona. There was a high proportion of smokers in both sexes. Alcohol consumption was four times higher among men than women; high proof beverages were becoming the most common drinks. Coffee was the caffeine drink consumed by almost the whole population studied. Although cannabis derivatives had been tried at least once by almost all the students, regular consumers were almost non-existent. Amphetamine consumption was restricted to examination periods. The use of opiates, cocaine, hallucinogens, and solvents was rare for the sample. Results from this study are compared with those from similar surveys conducted 5 and 10 years ago.

Novel strategies for sample preparation in forensic toxicology.

PubMed

Samanidou, Victoria; Kovatsi, Leda; Fragou, Domniki; Rentifis, Konstantinos

2011-09-01

This paper provides a review of novel strategies for sample preparation in forensic toxicology. The review initially outlines the principle of each technique, followed by sections addressing each class of abused drugs separately. The novel strategies currently reviewed focus on the preparation of various biological samples for the subsequent determination of opiates, benzodiazepines, amphetamines, cocaine, hallucinogens, tricyclic antidepressants, antipsychotics and cannabinoids. According to our experience, these analytes are the most frequently responsible for intoxications in Greece. The applications of techniques such as disposable pipette extraction, microextraction by packed sorbent, matrix solid-phase dispersion, solid-phase microextraction, polymer monolith microextraction, stir bar sorptive extraction and others, which are rapidly gaining acceptance in the field of toxicology, are currently reviewed.

Psilocybin impairs high-level but not low-level motion perception.

PubMed

Carter, Olivia L; Pettigrew, John D; Burr, David C; Alais, David; Hasler, Felix; Vollenweider, Franz X

2004-08-26

The hallucinogenic serotonin(1A&2A) agonist psilocybin is known for its ability to induce illusions of motion in otherwise stationary objects or textured surfaces. This study investigated the effect of psilocybin on local and global motion processing in nine human volunteers. Using a forced choice direction of motion discrimination task we show that psilocybin selectively impairs coherence sensitivity for random dot patterns, likely mediated by high-level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors. These results are in line with those observed within schizophrenic populations and are discussed in respect to the proposition that psilocybin may provide a model to investigate clinical psychosis and the pharmacological underpinnings of visual perception in normal populations.

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.

Is it time to revisit the role of psychedelic drugs in enhancing human creativity?

PubMed

Sessa, B

2008-11-01

Human creativity is difficult to define and measure, but it is undoubtedly an important cognitive process. This makes it an interesting challenge for modern neuroscientific exploration - especially given the current interest in developing cognitive enhancers for commercial and clinical uses. There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies - by modern research standards - was merely anecdotal. Nevertheless, with today's current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.

Identification of N,N-dimethyltryptamine and beta-carbolines in psychotropic ayahuasca beverage.

PubMed

Gambelunghe, Cristiana; Aroni, Kyriaki; Rossi, Riccardo; Moretti, Luca; Bacci, Mauro

2008-10-01

Recently many people have shown great interest in traditional indigenous practices and popular medicine, involving the ingestion of natural psychotropic drugs. We received a request to analyze and determine the nature of a dark green liquid with a dark brown plant sediment, which the police had seized at an airport and inside the home of a person belonging to the 'Santo Daime' religious movement. Gas chromatography/mass spectrometry analysis of the extract identified N,N-dimethyltryptamine, a potent hallucinogen, and the beta-carboline alkaloids harmine and harmaline, revealing monoamine oxidase A-inhibiting properties. These substances are typical components of Ayahuasca, a South American psychotropic beverage obtained by boiling the bark of the liana Banisteriopsis caapi together with the leaves of various admixture plants, principally Psychotria viridis.

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.

The pharmacological effects of Salvia species on the central nervous system.

PubMed

Imanshahidi, Mohsen; Hosseinzadeh, Hossein

2006-06-01

Salvia is an important genus consisting of about 900 species in the family Lamiaceae. Some species of Salvia have been cultivated world wide for use in folk medicine and for culinary purposes. The dried root of Salvia miltiorrhiza, for example, has been used extensively for the treatment of coronary and cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis, S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with important pharmacological effects. In this review, the pharmacological effects of Salvia species on the central nervous system will be reviewed. These include sedative and hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic, memory enhancing, anticonvulsant, neuroprotective and antiparkinsonian activity, as well as the inhibition of ethanol and morphine withdrawal syndrome.

[The substance experience, a history of LSD].

PubMed

Beck, François; Bonnet, Nicolas

2013-04-01

This article reviews the recent knowledge on LSD stemming from various disciplines among which pharmacology, sociology and epidemiology. The d-lysergic acid diethylamide (LSD) is a particularly powerful hallucinogenic substance. It produces distortions and hearing, visual and tactile hallucinations. Rarely used (only 1.7% of people aged 15-64 years old have tried it in their lifetime), this very powerful drug generates a strong apprehension within the general population, but the ethnographical studies show that its image seems rather good among illicit drug users. This representation relies both on the proper effects of this substance and also on the history of LSD very closely linked to the counterculture characteristic of the years 1960-1970. © 2013 médecine/sciences – Inserm / SRMS.

Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

PubMed Central

Yu, Shaobin; Zhu, Ling; Shen, Qiang; Bai, Xue; Di, Xuhui

2015-01-01

Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level. PMID:25861156

Simultaneous determination of 11 designated hallucinogenic phenethylamines by ultra-fast liquid chromatography with fluorescence detection.

PubMed

Min, Jun Zhe; Shimizu, Yoshiha; Toyo'oka, Toshimasa; Inagaki, Shinsuke; Kikura-Hanajiri, Ruri; Goda, Yukihiro

2008-10-01

To avoid the spreading of illegal drugs, a designated drug regulation system was introduced along with revision of the Pharmaceutical Affairs Law in Japan in 2006, and 32 substances including phenethylamine-type drugs were listed in April 2007. In this study, a new simultaneous determination method, based on ultra-fast liquid chromatography coupled with fluorescence detection (UFLC-FL), was developed for the 11 designated phenethylamine drugs. The phenethylamines were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) at 60 degrees C for 2h in 0.1M borax (pH 9.3). The resulting 11 fluorophores were completely separated by reversed-phase chromatography using an ACQUITY UPLC BEH C(18) column (2.1 mm x 100 mm 1.7 microm) and fluorometrically detected at 550 nm (excitation at 450 nm). The calibration curves obtained from the peak areas versus the injection amounts of the phenethylamines showed a good linearity. The limits of detection (signal-to-noise ratio of 3: S/N=3) on the chromatogram were in the range from 10 fmol (PMMA) to 2.5pmol (MMDA-2). Good accuracy (%) and precision (CV) by intra-day assay and inter-day assay were also obtained using the present procedure. The method was applied to the qualitative and quantitative analyses of phenethylamine in real products obtained from the Japanese market. As the results, BDB (0.24 mg/mg), MMDA-2 (0.98 mg/mL) and 2C-I (0.016 mg/mg) were identified from the different products (powder, liquid and mushroom like). Because the procedure is simple, selective and sensitive, the present method seems to be useful for the qualitative and quantitative analyses of the designated phenethylamines in various samples including biological specimens.

Use of synthetic stimulants and hallucinogens in a cohort of electronic dance music festival attendees.

PubMed

Mohr, Amanda L A; Friscia, Melissa; Yeakel, Jillian K; Logan, Barry K

2018-01-01

Novel psychoactive substances (NPS), often characterized as unregulated psychoactive compounds designed to circumvent existing legislation, have become mainstream on the illicit drug market. Because of their physical and mind-altering properties, NPS may be deliberately or inadvertently ingested at electronic dance music (EDM) festivals to enhance the attendees' appreciation of the music and overall experience. Their widespread use at EDM festivals have been well documented and several adverse events and fatalities associated with NPS ingestion have been reported in the United States. The diversity and rapid turnover in the prevalence of any particular NPS at any given point of time has created several challenges for public health officials, law enforcement, and forensic science communities. Epidemiological studies are often published long after drugs have cycled through the peak of their popularity with users and the scope of testing frequently failing to detect, identify or report the most recently available drugs. The aims of the study included discovering emerging NPS, ascertaining their overall prevalence and determining patterns of use and trends within this targeted population. Over the course of two years, biological samples were collected from 396 (126 blood samples; 227 urine samples; and 384 oral fluid samples) EDM festival attendees. Additionally, survey data regarding prescription and recreational drug use within the last week were collected with follow-up questions related to what substance(s) the person had ingested, amount taken, when the substance was last taken and perceived effects. All biological samples were screened and subsequently confirmed and/or quantified, when appropriate. In response to survey questions, 72% of the participants reported using a recreational drug or medicinal substance within the last week. Users most commonly reported using marijuana and alcohol, followed by "Molly" and cocaine. Of the 396 individuals tested, approximately 75% of the population was positive in at least one biological specimen for drugs and/or alcohol. Of those positive samples, 36% were confirmed to contain one or more NPS and/or 3,4-methylenedioxy-methamphetamine (MDMA). High rates of turnover and spikes in popularity related to NPS are supported by samples confirming positive for alpha-PVP in 2014, however, one year later not a single case was positive for alpha-PVP, and instead increasing numbers of subjects were positive for ethylone. Copyright © 2017 Elsevier B.V. All rights reserved.

The hallucinogen DOI reduces low-frequency oscillations in rat prefrontal cortex: reversal by antipsychotic drugs.

PubMed

Celada, Pau; Puig, M Victoria; Díaz-Mataix, Llorenç; Artigas, Francesc

2008-09-01

Perceptual and psychic alterations and thought disorder are fundamental elements of schizophrenia symptoms, a pathology associated with an abnormal macro- and microcircuitry of several brain areas including the prefrontal cortex (PFC). Alterations in information processing in PFC may partly underlie schizophrenia symptoms. The 5-HT(2A/2C) agonist DOI and antipsychotic drugs were administered to anesthetized rats. Single unit and local field potential (LFP) extracellular recordings were made in medial PFC (mPFC). Electrolytic lesions were performed in the thalamic nuclei. DOI markedly disrupts cellular and network activity in rat PFC. DOI altered pyramidal discharge in mPFC (39% excited, 27% inhibited, 34% unaffected; n = 51). In all instances, DOI concurrently reduced low-frequency oscillations (.3-4 Hz; power spectrum: .25 +/- .02 and .14 +/- .01 microV(2) in basal conditions and after 50-300 microg/kg intravenous (i.v.) DOI, respectively; n = 51). Moreover, DOI disrupted the temporal association between the active phase of LFP and pyramidal discharge. Both effects were reversed by M100907 (5-HT(2A) receptor antagonist) and were not attenuated by thalamic lesions, supporting an intracortical origin of the effects of DOI. The reduction in low-frequency oscillations induced by DOI was significantly reversed by the antipsychotic drugs haloperidol (.1-.2 mg/kg i.v.) and clozapine (1 mg/kg i.v.). DOI disorganizes network activity in PFC, reducing low-frequency oscillations and desynchronizing pyramidal discharge from active phases of LFP. These effects may underlie DOI's psychotomimetic action. The reversal by clozapine and haloperidol indicates that antipsychotic drugs may reduce psychotic symptoms by normalizing an altered PFC function.

Could Hallucinogens Induce Permanent Pupillary Changes in (Ab)users? A Case Report from New Zealand

PubMed Central

2017-01-01

An eighteen-year-old female patient of the Caucasian ethnicity from Australasia presented with a persistently dilated pupil causing her discomfort and occasional burning sensation when she is outdoors due to oversensitivity to sunlight. However, her pupillary reaction to light (pupillary light reflex) was intact. The patient is a known user of psychedelic substances (entheogens) including LSD, NBOMe, psilocybin, and DMT. The condition affects both eyes to the same extent. Thorough medical, neurological, and radiological examinations, including an EEG and an MRI of the head and neck region, were completely normal. All these tests failed to detect any pathophysiological or anatomical abnormalities. The patient is a known case of chronic endogenous depression in association with attention deficit hyperactivity disorder, for which she is taking citalopram and Ritalin, respectively. There was neither a family history nor a similar congenital condition in her family. PMID:28948056

To use or not to use: an update on licit and illicit ketamine use

PubMed Central

Li, Jih-Heng; Vicknasingam, Balasingam; Cheung, Yuet-Wah; Zhou, Wang; Nurhidayat, Adhi Wibowo; Jarlais, Don C Des; Schottenfeld, Richard

2011-01-01

Ketamine, a derivative of phencyclidine that was developed in the 1960s, is an anesthetic and analgesic with hallucinogenic effects. In this paper, the pharmacological and toxicological effects of ketamine are briefly reviewed. Ketamine possesses a wide safety margin but such a therapeutic benefit is somewhat offset by its emergence phenomenon (mind-body dissociation and delirium) and hallucinogenic effects. The increasing abuse of ketamine, initially predominantly in recreational scenes to experience a “k-hole” and other hallucinatory effects but more recently also as a drug abused during the workday or at home, has further pushed governments to confine its usage in many countries. Recently, urinary tract dysfunction has been associated with long-term ketamine use. In some long-term ketamine users, such damage can be irreversible and could result in renal failure and dialysis. Although ketamine has not yet been scheduled in the United Nations Conventions, previous studies using different assessment parameters to score the overall harms of drugs indicated that ketamine may cause more harm than some of the United Nations scheduled drugs. Some countries in Southeast and East Asia have reported an escalating situation of ketamine abuse. Dependence, lower urinary tract dysfunction, and sexual impulse or violence were the most notable among the ketamine-associated symptoms in these countries. These results implied that the danger of ketamine may have been underestimated previously. Therefore, the severity levels of the ketamine-associated problems should be scrutinized more carefully and objectively. To prevent ketamine from being improperly used and evolving into an epidemic, a thorough survey on the prevalence and characteristics of illicit ketamine use is imperative so that suitable policy and measures can be taken. On the other hand, recent findings that ketamine could be useful for treating major depressive disorder has given this old drug a new impetus. If

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD).

PubMed

Brandt, Simon D; Kavanagh, Pierce V; Westphal, Folker; Stratford, Alexander; Elliott, Simon P; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L

2016-09-01

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a 'research chemical' in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50  = 349.6 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.

PubMed

Buchborn, Tobias; Schröder, Helmut; Dieterich, Daniela C; Grecksch, Gisela; Höllt, Volker

2015-03-15

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.025 and 0.25 mg/kg, i.p.) induce a ketanserin-sensitive (0.5 mg/kg, i.p., 30-min pretreatment) increase in shaking behaviour (including head twitches and wet dog shakes), which with repeated application (7× in 4 ds) is undermined by tolerance. Tolerance to DOB, as indexed by DOB-sensitive [(3)H]spiroperidol and DOB induced [(35)S]GTP-gamma-S binding, is accompanied by a frontocortical decrease in 5-HT2A binding sites and 5-HT2 signalling, respectively; glutamate-sensitive [(3)H]glutamate binding sites, in contrast, remain unchanged. As to LSD, 5-HT2 signalling and 5-HT2A binding, respectively, are not or only marginally affected, yet [(3)H]glutamate binding is significantly decreased. Correlation analysis interrelates tolerance to DOB to the reduced 5-HT2A (r=.80) as well as the unchanged [(3)H]glutamate binding sites (r=.84); tolerance to LSD, as opposed, shares variance with the reduction in [(3)H]glutamate binding sites only (r=.86). Given that DOB and LSD both induce tolerance, one correlating with 5-HT2A, the other with glutamate receptor adaptations, it might be inferred that tolerance can arise at either level. That is, if a hallucinogen (like LSD in our study) fails to induce 5-HT2A (down-)regulation, glutamate receptors (activated postsynaptic to 5-HT2A related glutamate release) might instead adapt and thus prevent further overstimulation of the cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo long-term kinetics of radiolabeled n,n-dimethyltryptamine and tryptamine.

PubMed

Vitale, Arturo A; Pomilio, Alicia B; Cañellas, Carlos O; Vitale, Martín G; Putz, Eva Maria; Ciprian-Ollivier, Jorge

2011-06-01

N,N-dimethyltryptamine (DMT), a strong psychodysleptic drug, has been found in higher plants, shamanic hallucinogenic beverages, and the urine of schizophrenic patients. The aim of this work was to gain better knowledge on the relationship between this drug and hallucinogenic processes by studying DMT behavior in comparison with tryptamine. (131)I-labeled DMT and tryptamine were injected into rabbits. γ-Camera and biodistribution studies were performed. Brain uptake, plasma clearance, and renal excretion were assessed for each indolealkylamine. DMT and tryptamine showed different behavior when brain uptake, residence time, and excretion were compared. Labeled DMT entered the brain 10 s after injection, crossed the blood-brain barrier, and bound to receptors; then it was partially renally excreted. It was detected in urine within 24 h after injection and remained in the brain, even after urine excretion ceased; up to 0.1% of the injected dose was detected at 7 d after injection in the olfactory bulb. In contrast, tryptamine was rapidly taken up in the brain and fully excreted 10 min after injection. To our knowledge, this is the first demonstration that exogenous DMT remains in the brain for at least 7 d after injection. Although labeled DMT and tryptamine behave as agonists for at least 5-hydroxytryptamine 2A receptor, 5-hydroxytryptamine 2C receptor, trace amine-associated receptor, and σ-1 putative receptor targets, binding to the latter can explain the different behavior of labeled DMT and tryptamine in the brain. The persistence in the brain can be further explained on the basis that DMT and other N,N-dialkyltryptamines are transporter substrates for both the plasma membrane serotonin transporter and the vesicle monoamine transporter 2. Furthermore, storage in vesicles prevents DMT degradation by monoamine oxidase. At high concentrations, DMT is taken up by the serotonin transporter and further stored in vesicles by the vesicle monoamine transporter 2, to be

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats.

PubMed

Noworyta-Sokołowska, Karolina; Kamińska, Katarzyna; Kreiner, Grzegorz; Rogóż, Zofia; Gołembiowska, Krystyna

2016-11-01

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.

Drug discrimination studies with ibogaine.

PubMed

Helsley, S; Rabin, R A; Winter, J C

2001-01-01

The results of the studies described here support the hypothesis that ibogaine produces its effects via selective interactions with multiple receptors. It appears that 5-HT2A, 5-HT2C, and sigma 2 receptors are involved in mediating the stimulus effects of ibogaine. In addition, opiate receptors may also be involved. In contrast, sigma 1, PCP/MK-801, 5-HT3, and 5-HT1A receptors do not appear to play a major role. Ibogaine's hallucinogenic effects may be explained by its interactions with 5-HT2A and 5-HT2C receptors, while its putative antiaddictive properties may result from its interactions with sigma 2 and opiate receptors. Alternatively, the possibility that ibogaine's hallucinogenic properties underlie its antiaddictive effects, as previously suggested (34), would support a role for 5-HT2 receptors in mediating the reported therapeutic effects of ibogaine. Certainly many questions remain regarding ibogaine's mechanism of action. Although drug discrimination will be useful for answering some of those questions, the true potential of this technique is realized whin it is combined with other techniques. The next few years promise to be fruitful with respect to our understanding of this agent. Reasons supporting this belief include advances in the study of sigma receptors, interest in ibogaine's effects on second messenger systems, and the development of ibogaine congeners such as 18-methoxycoronaridine (35). In conclusion, the aforementioned studies should serve to guide further endeavors. Pertinent questions have been generated: What is the role of sigma receptors in the effects of ibogaine, especially with regard to addiction? How does ibogaine affect opiate neurotransmission? What effects, if any, do the Harmala alkaloids have on addiction phenomena? What is the mechanism of action of harmaline? Can 10-hydroxyibogamine serve as a discriminative stimulus and, if so, what receptor interactions mediate its stimulus effects? Does the ibogaine-trained stimulus

Illicit drug use in late pregnancy associated with stillbirth and eclampsia

PubMed Central

Scott, Katherine; Fagermo, Narelle; Callaway, Leonie; Lust, Karin

2010-01-01

We present the case of a 20-year-old student with an undiagnosed pregnancy who had taken ecstasy and LSD (lysergic acid diethylamide). Twenty-four hours later she delivered a stillborn term infant, and subsequently developed eclampsia with seizures, hypertension and proteinuria. Illicit drug use is relatively common in women of child-bearing age in Australia, and is a risk factor for adverse obstetric outcomes. Ecstasy (MDMA [3,4-methylenedioxymethamphetamine]) is a sympathomimetic amine, similar to amphetamine in its cardiovascular effects. LSD is a hallucinogen with complex pharmacology and has potential for significant compromise of placental blood flow. We propose that the combined vasoconstrictive effects of MDMA and LSD caused placental ischaemia, contributing to the fetal death and precipitating a cascade of endothelial dysfunction which resulted in an eclamptic syndrome. PMID:27579073

Determination of psilocybin in Psilocybe semilanceata by capillary zone electrophoresis.

PubMed

Pedersen-Bjergaard, S; Sannes, E; Rasmussen, K E; Tønnesen, F

1997-07-04

A capillary zone electrophoretic (CZE) method was developed for the rapid determination of psilocybin in Psilocybe semilanceata. Following a simple two step extraction with 3.0+2.0 ml methanol, the hallucinogenic compound was effectively separated from matrix components by CZE utilizing a 10 mM borate-phosphate running buffer adjusted to pH 11.5. The identity of psilocybin was confirmed by migration time information and by UV spectra, while quantitation was accomplished utilizing barbital as internal standard. The calibration curve for psilocybin was linear within 0.01-1 mg/ml, while intra-day and inter-day variations of quantitative data were 0.5 and 2.5% R.S.D., respectively. In addition to psilocybin, the method was also suitable for the determination of the structurally related compound baeocystin.

Bath salts and synthetic cathinones: An emerging designer drug phenomenon

PubMed Central

German, Christopher L.; Fleckenstein, Annette E.; Hanson, Glen R.

2014-01-01

The synthetic cathinones are an emerging class of designer drugs abused for psychostimulant and hallucinogenic effects similar to cocaine, methylenedioxymethamphetamine (MDMA), or other amphetamines. Abuse of synthetic cathinones, frequently included in products sold as ‘bath salts’, became prevalent in early 2009, leading to legislative classification throughout Europe in 2010 and schedule I classification within the United States in 2011. Recent pre-clinical and clinical studies indicate dysregulation of central monoamine systems are a principal mechanism of synthetic cathinone action and presumably underlie the behavioral effects and abuse liability associated with these drugs. This review provides insight into the development of synthetic cathinones as substances of abuse, current patterns of their abuse, known mechanisms of their action and toxicology, and the benefits and drawbacks of their classification. PMID:23911668

A case of pediatric age anticholinergic intoxication due to accidental Datura stramonium ingestion admitting with visual hallucination.

PubMed

Şanlıdağ, Burçin; Derinöz, Okşan; Yıldız, Nagehan

2014-01-01

Datura stramonium (DS) is a hallucinogenic plant that can produce anticholinergic toxicity because of its significant concentrations of toxic alkaloids, such as atropine, hyoscyamine, and scopolamine. DS grows in both rural and urban areas in Turkey. Clinical findings of toxicity are similar to those of atropine toxicity. DS abuse is common among adolescents because of its hallucinatory effects. However, accidental DS poisoning from contaminated food is very rare. Accidental poisonings are commonly seen among children. Children are more prone to the toxic effects of atropine; ingestion of even a small amount can cause serious central nervous system symptoms. Treatment is supportive; antidote treatment is given rarely. An eight-year-old male with accidental DS poisoning who presented to the Pediatric Emergency Department with aggression, agitation, delirium, and visual hallucinations is reported.

Effects of varied doses of psilocybin on time interval reproduction in human subjects.

PubMed

Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

2008-04-11

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

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.

Drugs and sexual behavior.

PubMed

Bruno, Antonio; Scimeca, Giuseppe; Marino, Antonio G; Mento, Carmela; Micò, Umberto; Romeo, Vincenzo M; Pandolfo, Gianluca; Zoccali, Rocco; Muscatello, Maria R A

2012-01-01

This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed.

Strategies for the capillary electrophoretic separation of indole alkaloids in Psilocybe semilanceata.

PubMed

Pedersen-Bjergaard, S; Rasmussen, K E; Sannes, E

1998-01-01

While the hallucinogenic mushrooms Psilocybe semilanceata have previously been analyzed for the indole alkaloids psilocybin and baeocystin by capillary zone electrophoresis (CZE) at pH 11.5, the present work focused on the development of an alternative and complementary capillary electrophoretic method for their identification. Owing to their structural similarity and zwitterionic nature, the compounds were difficult to resolve based on different interactions with cationic or anionic micelles. However, while the attempts with micellar electrokinetic chromatography (MEKC) were unsuccessful, rapid derivatization with propyl chloroformate and reanalysis by CZE at pH 11.5 was effective to support identification of the two indole alkaloids. Psilocin was difficult to analyze by CZE at pH 11.5 owing to comigration with the electroosmotic flow. For this compound, the pH of the running buffer was reduced to 7.2 to effectively enhance the electrophoretic mobility.

Analysis of psilocin, bufotenine and LSD in hair.

PubMed

Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

2015-03-01

A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

PubMed

Oram, Matthew

2016-09-01

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. © The Author(s) 2016.

Health behaviours in a Canadian community college sample: prevalence of drug use and interrelationships among behaviours.

PubMed

Mathieson, C M; Faris, P D; Stam, H J; Egger, L A

1992-01-01

This study investigated the prevalence of drug use among a Canadian college sample and the covariation of drug taking and other health-related behaviours. A representative sample of students at a community college in Alberta were interviewed using telephone surveys, mail-in questionnaires and face-to-face interviews. Data was collected on drug, alcohol and caffeine use, cigarette smoking, eating habits, sleep habits and exercise. While use of illicit drugs did not appear to be widespread, alcohol appeared to be a primary substance abuse problem for a minority of subjects. Factor analysis indicated that the various health habits did not form one dimension of health-related behaviours. Four separate factors emerged: abusive drinking, eating habits, a drug use factor (caffeine intake, smoking, cannabis and hallucinogen use), and exercise levels. Findings are discussed in terms of their implications for future research, treatment and intervention.

Drug Policy and Indigenous Peoples.

PubMed

Burger, Julian; Kapron, Mary

2017-06-01

This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens. They are also victims of the drug producers who remove them from their lands or forcibly recruit them into the production process. As indigenous peoples are caught in the violent world of illicit drug production, law enforcement often targets them first, resulting in disproportionate rates of criminalization and incarceration.

The effects of intracranial administration of hallucinogens on operant behavior in the rat. I. Lysergic acid diethylamide.

PubMed

Mokler, D J; Stoudt, K W; Sherman, L C; Rech, R H

1986-10-01

Lysergic acid diethylamide (LSD) was infused in one microliter volumes into discrete brain regions of rats trained to press a bar for food reinforcement. The sites were chosen as major areas of the brain 5-hydroxytryptamine (5HT) system: the dorsal and median raphe nuclei, dorsal hippocampus, lateral habenular nuclei, and the prefrontal cortex. Following training in a fixed ratio-40 (FR-40) operant behavior rats were implanted for the lateral habenular nuclei, dorsal hippocampus and the prefrontal cortex. Following recovery from surgery, LSD (8.6 to 86 micrograms) or vehicle was infused immediately before a daily operant session. Infusion of vehicle was inactive. LSD produced a dose-dependent decrease in reinforcements and an increase in 10-sec periods of non-responding (pause intervals). LSD was significantly more potent when infused into the dorsal raphe nucleus than following intracerebroventricular (ICV) administration, whereas LSD was less potent when infused into the median raphe, lateral habenula or dorsal hippocampus. ED50s for increases in pause intervals were 9, 13, 23, 25, and 54 micrograms for infusion into the dorsal raphe, prefrontal cortex, dorsal hippocampus, median raphe, and lateral habenular nuclei, respectively. The ED50 for ICV administration in a previous study was 15 micrograms. The ED50 of LSD placed into the prefrontal cortex did not differ significantly from that of the ICV infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of adolescent suicide across patterns of drug use: a nationally representative study of high school students in the United States from 1999 to 2009.

PubMed

Wong, Shane Shucheng; Zhou, Bo; Goebert, Deborah; Hishinuma, Earl S

2013-10-01

Substance use is associated with suicidal ideation, planning and attempts among adolescents, but it is unclear how this association varies across different types and number of substances. This study examined the association between patterns of substance use and suicidality among a nationally representative sample of high school students in the United States during the last decade. Data from the 2001 to 2009 Youth Risk Behavior Survey including 73,183 high school students were analyzed. Logistic regression analyses examined the association between lifetime use of ten common substances of abuse (alcohol, cocaine, ecstasy, hallucinogens, heroin, inhalants, marijuana, methamphetamines, steroids, and tobacco) and four measures of suicidality over the last year (suicidal ideation, suicide plan, suicide attempt, and severe suicide attempt requiring medical attention), controlling for potential confounders (socio-demographic variables, interpersonal violence, sexual intercourse, and symptoms of depression and eating disorder). Among the ten substances, univariate analysis demonstrates that adolescents reporting a history of heroin use have the strongest association with suicidal ideation, suicide plan, suicide attempts and severe suicide attempts in the last year (odds ratio = 5.0, 5.9, 12.0, and 23.6 compared to non-users), followed by users of methamphetamines (OR = 4.3-13.1) and steroids (OR = 3.7-11.8). Cocaine, ecstasy, hallucinogens and inhalants had a moderate association with suicidality (OR = 3.1-10.8). Users of marijuana, alcohol and tobacco also had an increased odds ratio of suicidality (OR = 1.9-5.2). The association between each of ten substances and the four measures of suicidality remained significant with multivariate analysis controlling for multiple confounders (p < 0.05), except for the association between alcohol use and severe suicide attempts. The seven illicit substances had a stronger association with severe suicide attempts as compared to all

Teotlaqualli: the psychoactive food of the Aztec gods.

PubMed

Elferink, J G

1999-01-01

The Aztecs in pre-Columbian Mexico used not only a large number of single hallucinogens, they also used some combinations. The present article describes reports of the use of teotlaqualli, an unction prepared from ololiuhqui and picietl, with a large number of additions. The work of the chroniclers of pre-Columbian Mexico served as a source of information. The teotlaqualli was offered to the gods, for whom it served as food. The Aztec priests smeared themselves with this unction, to lose fear and to get the appropriate state of mind to serve the Aztec gods. A few cases are reported in which the Aztec emperor or soldiers were smeared with teotlaqualli. It is suggested that the black color of some Aztec deities, as depicted in the codices, was due to anointment with teotlaqualli. In addition to its use for psychoactive purposes, teotlaqualli was used in medicine under the name teopatli.

Drug Policy and Indigenous Peoples

PubMed Central

Kapron, Mary

2017-01-01

Abstract This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens. They are also victims of the drug producers who remove them from their lands or forcibly recruit them into the production process. As indigenous peoples are caught in the violent world of illicit drug production, law enforcement often targets them first, resulting in disproportionate rates of criminalization and incarceration. PMID:28630559

The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction.

PubMed

Laviolette, S R; Grace, A A

2006-07-01

Cannabinoids represent one of the most widely used hallucinogenic drugs and induce profound alterations in sensory perception and emotional processing. Similarly, the dopamine (DA) neurotransmitter system is critical for the central processing of emotion and motivation. Functional disturbances in either of these neurotransmitter systems are well-established correlates of the psychopathological symptoms and behavioral manifestations observed in addiction and schizophrenia. Increasing evidence from the anatomical, pharmacological and behavioral neuroscience fields points to complex functional interactions between these receptor systems at the anatomical, pharmacological and neural systems levels. An important question relates to whether these systems act in an orchestrated manner to produce the emotional processing and sensory perception deficits underlying addiction and schizophrenia. This review describes evidence for functional neural interactions between cannabinoid and DA receptor systems and how disturbances in this neural circuitry may underlie the aberrant emotional learning and processing observed in disorders such as addiction and schizophrenia.

Ayahuasca in adolescence: a preliminary psychiatric assessment.

PubMed

Da Silveira, Dartiu Xavier; Grob, Charles S; de Rios, Marlene Dobkin; Lopez, Enrique; Alonso, Luisa K; Tacla, Cristiane; Doering-Silveira, Evelyn

2005-06-01

Ayahuasca is believed to be harmless for those (including adolescents) drinking it within a religious setting. Nevertheless controlled studies on the mental/ psychiatric status of ritual hallucinogenic ayahuasca concoction consumers are still lacking. In this study, 40 adolescents from a Brazilian ayahuasca sect were compared with 40 controls matched on sex, age, and educational background for psychiatric symptomatology. Screening scales for depression, anxiety, alcohol consumption patterns (abuse), attentional problems, and body dysmorphic disorders were used. It was found that, compared to controls, considerable lower frequencies of positive scoring for anxiety, body dismorphism, and attentional problems were detected among ayahuasca-using adolescents despite overall similar psychopathological profiles displayed by both study groups. Low frequencies of psychiatric symptoms detected among adolescents consuming ayahuasca within a religious context may reflect a protective effect due to their religious affiliation. However further studies on the possible interference of other variables in the outcome are necessary.

Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine.

PubMed

Halpin, Laura E; Collins, Stuart A; Yamamoto, Bryan K

2014-02-27

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as 'bath salts' that have gained popularity among drug abusers. © 2013.

Psychedelics and schizophrenia.

PubMed

González-Maeso, Javier; Sealfon, Stuart C

2009-04-01

Research on psychedelics such as lysergic acid diethylamide (LSD) and dissociative drugs such as phencyclidine (PCP) and the symptoms, neurochemical abnormalities and treatment of schizophrenia have converged. The effects of hallucinogenic drugs resemble some of the core symptoms of schizophrenia. Some atypical antipsychotic drugs were identified by their high affinity for serotonin 5-HT(2A) receptors, which is also the target of LSD-like drugs. Several effects of PCP-like drugs are strongly affected by both 5-HT(2A) and metabotropic glutamate 2/3 receptor modulation. A serotonin-glutamate receptor complex in cortical pyramidal neurons has been identified that might be the target both of psychedelics and the atypical and glutamate classes of antipsychotic drugs. Recent results on the receptor, signalling and circuit mechanisms underlying the response to psychedelic and antipsychotic drugs might lead to unification of the serotonin and glutamate neurochemical hypotheses of schizophrenia.

Towards an Explanation of Subjective Ketamine Experiences among Young Injection Drug Users

PubMed Central

LANKENAU, STEPHEN E.; SANDERS, BILL; BLOOM, JENNIFER JACKSON; HATHAZI, DODI

2008-01-01

Ketamine is a dissociative anesthetic with powerful sedative and hallucinogenic properties. Despite the wide variability in reported subjective experiences, no study has attempted to describe the particular factors that shape these experiences. This manuscript is based upon a sample of 213 young injection drug users recruited in New York, New Orleans, and Los Angeles with histories of ketamine use. Qualitative interviews focused on specific ketamine events, such as first injection of ketamine, most recent injection of ketamine, and most recent experience sniffing ketamine. Findings indicate that six factors impacted both positive and negative ketamine experiences: polydrug use, drug using history, mode of administration, quantity and quality of ketamine, user group, and setting. Most subjective experiences during any given ketamine event were shaped by a combination of these factors. Additionally, subjective ketamine experiences were particularly influenced by a lifestyle characterized by homelessness and traveling. PMID:18941540

Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine

PubMed Central

Halpin, Laura E.; Collins, Stuart A.; Yamamoto, Bryan K.

2013-01-01

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as ‘bath salts’ that have gained popularity amongst drug abusers. PMID:23892199

Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter.

PubMed

Jacobs, Miriam T; Zhang, Yuan-Wei; Campbell, Scott D; Rudnick, Gary

2007-10-05

Ibogaine, a hallucinogenic alkaloid with purported anti-addiction properties, inhibited serotonin transporter (SERT) noncompetitively by decreasing V(max) with little change in the K(m) for serotonin (5-HT). Ibogaine also inhibited binding to SERT of the cocaine analog 2beta-2-carbomethoxy-3-(4-[(125)I]iodophenyl)tropane. However, inhibition of binding was competitive, increasing the apparent K(D) without much change in B(max). Ibogaine increased the reactivity of cysteine residues positioned in the proposed cytoplasmic permeation pathway of SERT but not at nearby positions out of that pathway. In contrast, cysteines placed at positions in the extracellular permeation pathway reacted at slower rates in the presence of ibogaine. These results are consistent with the proposal that ibogaine binds to and stabilizes the state of SERT from which 5-HT dissociates to the cytoplasm, in contrast with cocaine, which stabilizes the state that binds extracellular 5-HT.

Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material.

PubMed

Mazoyer, Cédric; Carlier, Jérémy; Boucher, Alexandra; Péoc'h, Michel; Lemeur, Catherine; Gaillard, Yvan

2013-11-01

We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC-MS/MS after liquid-liquid extraction (Toxi-tubes A(®)). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7.2%. Moreover, systematic toxicological analyses of biological samples showed the presence of diazepam and methadone in therapeutic concentrations. Death was attributed to the ingestion of a substantial quantity of iboga in the context of simultaneous methadone and diazepam consumption. © 2013 American Academy of Forensic Sciences.

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.

[The impact of psilocybin on visual perception and spatial orientation--neuropsychological approach].

PubMed

Jastrzebski, Mikolaj; Bala, Aleksandra

2013-01-01

Psilocybin is a substance of natural origin, occurring in hallucinogenic mushrooms (most common in the Psilocybe family). After its synthesis in 1958 research began on its psychoactive properties, particularly strong effects on visual perception and spatial orientation. Due to the very broad spectrum of psilocybin effects research began on the different ranges of its actions--including the effect on physiological processes (such as eye saccada movements). Neuro-imaging and neurophysiological research (positron emission tomography-PET and electroencephalography-EEG), indicate a change in the rate of metabolism of the brain and desync cerebral hemispheres. Experimental studies show the changes in visual perception and distortion from psilocybin in the handwriting style of patients examined. There are widely described subjective experiences reported by the subjects. There are also efforts to apply testing via questionnaire on people under the influence of psilocybin, in the context of the similarity of psilocybin-induced state to the initial stages of schizophrenia, as well as research aimed at creating an 'artificial' model of the disease.

[Use of psychoactive drugs by health sciences undergraduate students at the Federal University in Amazonas, Brazil].

PubMed

Lucas, Ana Cyra dos Santos; Parente, Rosana Cristina Pereira; Picanço, Neila Soares; Conceição, Denis Alvaci; Costa, Karen Regina Carim da; Magalhães, Igor Rafael dos Santos; Siqueira, João Cladirson Alves

2006-03-01

A survey was conducted with 521 undergraduate health sciences students from the Federal University in Amazonas, Manaus, Brazil. Lifetime alcohol consumption was reported by 87.7% students, as compared to 30.7% for tobacco, with the latter reported more frequently by males (39.7%). The most common illicit drugs were solvents (11.9%), marijuana (9.4%), amphetamines and anxiolytics (9.2% each), cocaine (2.1%), and hallucinogens (1.2%). The main reason for illicit drug use was curiosity. Lifetime use of anabolic steroids was reported by 2.1% of the students. Alcohol abuse in the previous 30 days was reported by 12.4% of the students. Events following drinking included: fights (4.7%), accidents (2.4%), classroom absenteeism (33.7%), and job absenteeism (11.8%). Another important finding was that 47.3% of students drove after drinking. Opinions on drug abuse and patterns agree with those from similar studies in other regions of Brazil.

Ayahuasca Alters Structural Parameters of the Rat Aorta.

PubMed

Pitol, Dimitrius L; Siéssere, Selma; Dos Santos, Rafael G; Rosa, Maria L N M; Hallak, Jaime E C; Scalize, Priscilla H; Pereira, Bruno F; Iyomasa, Melina M; Semprini, Marisa; Riba, Jordi; Regalo, Simone C H

2015-07-01

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT(1A/2A/2C) agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2-4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

A critical evaluation of reports associating ayahuasca with life-threatening adverse reactions.

PubMed

dos Santos, Rafael Guimarāes

2013-01-01

Ayahuasca is a botanical hallucinogenic preparation traditionally consumed by Northwestern Amazonian indigenous groups. Scientific evidence suggests good tolerability after acute administration of ayahuasca and also after years or even decades of its ritual consumption. Nevertheless, some scientific and media reports associate ayahuasca or some of its alkaloids with severe intoxications. The purpose of the present text is to do a critical evaluation of these reports. The evaluation of the cases highlights the fact that some lack accurate forensic/toxicological information, while others are not directly relevant to traditional ayahuasca preparations. These limitations reduce the possibility of an accurate risk assessment, which could indicate potential contraindications and susceptibilities for ayahuasca consumption. Nevertheless, even with these limitations, the cases suggest that previous cardiac and hepatic pathologies and current use of serotonergic drugs/medications are contraindications to ayahuasca use, and that caution should be taken when using different botanical species and extracted/synthetic alkaloids to prepare ayahuasca analogues.

Crystal Structure of an LSD-Bound Human Serotonin Receptor

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

Wacker, Daniel; Wang, Sheng; McCorvy, John D.

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatlymore » accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.« less

Chronic non-fatal Datura abuse in a patient of paranoid schizophrenia: a case report.

PubMed

Khanra, Sourav; Khess, C R J; Srivastava, Naveen

2015-04-01

A range of psychoactive substances used by patients suffering from schizophrenia varies and may include those which are fatal and may cause serious toxicity leading to death. We here present a case report of a patient suffering from paranoid schizophrenia, who was abusing Datura stramonium over a prolonged period. A 32 year old male presented with aggressive behaviour, irritability for 6 years and regular intake of Datura seeds for 3 years. After taking detailed history and mental status examination (MSE), diagnoses of paranoid schizophrenia and mental and behavioral disorder due to use of hallucinogen were made. He had shown improvement on standard treatment with antipsychotics. D. stramonium is recognized among emerging new psychoactive substances being used across the world. Among various theories we discuss self-medication hypothesis as a mediating factor for this case. Though D. stramonium is notorious for its life threatening sequelae, clinicians should be aware of its chronic abuse as self-medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

NASA Astrophysics Data System (ADS)

Lovell, Kimberly M.; Prevatt-Smith, Katherine M.; Lozama, Anthony; Prisinzano, Thomas E.

Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.

Crystal Structure of an LSD-Bound Human Serotonin Receptor.

PubMed

Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

2017-01-26

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT 2B . The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT 2B R and 5-HT 2A R-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

LSD, 5-HT (serotonin), and the evolution of a behavioral assay.

PubMed

Appel, James B; West, William B; Buggy, James

2004-01-01

Research in our laboratory, supported by NIDA and facilitated by Roger Brown, has indicated that serotonergic neuronal systems are involved in the discriminative stimulus effects of LSD. However, the only compounds that fully antagonize the LSD cue act at both serotonin (5-HT) and dopamine (DA) receptors. In addition, substitution for LSD in standard drug vs. no-drug (DND) discriminations does not necessarily predict either similar mechanisms of action or hallucinogenic potency because 'false positives' occur when animals are given drugs such as lisuride (LHM), quipazine, or, possibly, yohimbine. These effects can be greatly reduced by using drug vs. drug (D-D), drug vs. drug vs. no drug (D-ND), or drug vs. ' other' drug (saline, cocaine, pentobarbital) training procedures. Additional studies, in which drugs were administered directly into the cerebral ventricles or specific brain areas, suggest that structures containing terminal fields of serotonergic neurons might be involved in the stimulus effects of LSD.

Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

PubMed Central

Urigüen, L; Gil-Pisa, I; Munarriz-Cuezva, E; Berrocoso, E; Pascau, J; Soto-Montenegro, M L; Gutiérrez-Adán, A; Pintado, B; Madrigal, J L M; Castro, E; Sánchez-Blázquez, P; Ortega, J E; Guerrero, M J; Ferrer-Alcon, M; García-Sevilla, J A; Micó, J A; Desco, M; Leza, J C; Pazos, Á; Garzón, J; Meana, J J

2013-01-01

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia. The animal could provide valuable insights into phenotypic aspects of this psychiatric disorder. PMID:23340504

The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas

PubMed Central

Friston, K. J.

2010-01-01

This article explores the notion that Freudian constructs may have neurobiological substrates. Specifically, we propose that Freud’s descriptions of the primary and secondary processes are consistent with self-organized activity in hierarchical cortical systems and that his descriptions of the ego are consistent with the functions of the default-mode and its reciprocal exchanges with subordinate brain systems. This neurobiological account rests on a view of the brain as a hierarchical inference or Helmholtz machine. In this view, large-scale intrinsic networks occupy supraordinate levels of hierarchical brain systems that try to optimize their representation of the sensorium. This optimization has been formulated as minimizing a free-energy; a process that is formally similar to the treatment of energy in Freudian formulations. We substantiate this synthesis by showing that Freud’s descriptions of the primary process are consistent with the phenomenology and neurophysiology of rapid eye movement sleep, the early and acute psychotic state, the aura of temporal lobe epilepsy and hallucinogenic drug states. PMID:20194141

Modulations of the experience of self and time.

PubMed

Wittmann, Marc

2015-12-15

Empirical findings in the Cognitive Sciences on the relationship between feeling states and subjective time have led to the assumption that time perception entails emotional and interoceptive states. The perception of time would thereafter be embodied; the bodily self, the continuous input from the body is the functional anchor of phenomenal experience and the mental self. Subjective time emerges through the existence of the self across time as an enduring and embodied entity. This relation is prominently disclosed in studies on altered states of consciousness such as in meditative states, under the influence of hallucinogens as well as in many psychiatric and neurological conditions. An increased awareness of oneself coincides with an increased awareness of time. Conversely, a decreased awareness of the self is associated with diminished awareness of time. The body of empirical work within different conceptual frameworks on the intricate relationship between self and time is presented and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

The 2014 Philip S. Portoghese Medicinal Chemistry Lectureship: The "Phenylalkylaminome" with a Focus on Selected Drugs of Abuse.

PubMed

Glennon, Richard A

2017-04-13

The phenylalkylamine, particularly the phenylethylamine, moiety is a common structural feature found embedded in many clinically approved agents. Greater still is its occurrence in drugs of abuse. The simplest phenylethylamine, 2-phenylethylamine itself, is without significant central action when administered at moderate doses, but fairly simple structural modifications profoundly impact its pharmacology and result in large numbers of useful pharmacological tools, agents with therapeutic potential, and in drugs of abuse (e.g., hallucinogens, central stimulants, empathogens), the latter of which are the primary focus here. In vivo drug discrimination techniques and in vitro receptor/transporter methods have been applied to understand the actions of these phenylalkylamines and their mechanisms of action. Thus far, depending upon pendent substituents, certain receptors (e.g., serotonin receptors) and monoamine transporters (i.e., serotonin, dopamine, and norepinephrine transporters) have been implicated as playing major roles in the actions of these abused agents in a complex and, at times, interwoven manner.

The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.

PubMed

Morales-García, Jose A; de la Fuente Revenga, Mario; Alonso-Gil, Sandra; Rodríguez-Franco, María Isabel; Feilding, Amanda; Perez-Castillo, Ana; Riba, Jordi

2017-07-13

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.

Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

PubMed

Majić, Tomislav; Schmidt, Timo T; Gallinat, Jürgen

2015-03-01

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies. © The Author(s) 2015.

Perceived Ease of Access to Alcohol, Tobacco, and Other Substances in Rural and Urban US Students

PubMed Central

Warren, Jacob C.; Smalley, K. Bryant; Barefoot, K. Nikki

2015-01-01

Introduction Ease of access to substances has been shown to have a direct and significant relationship with substance use for school-aged children. Previous research involving rural samples of middle and high school students reveals that perceived ease of access to substances is a significant predictor of recent use among rural adolescents; however, it is unclear if perceived access to substances varies between rural and urban areas. The purpose of the current study was to examine rural-urban differences in perceived ease of access to alcohol, smoking and chewing tobacco, marijuana, and seven other substances in order to better inform and promote future substance use prevention and programming efforts in rural areas. Methods Data were analyzed from the 2013 Georgia Student Health Survey II, administered in all public and interested private/charter schools in the state of Georgia. A total of 513,909 students (18.2% rural) indicated their perceived ease of access to 11 substances on a 4-point Likert-type scale. Rural-urban differences were investigated using chi-square analysis. Results In general, it appeared the rural-urban differences fell along legal/illicit lines. For middle school students, a significant difference in perceived ease of access was found for each substance, with rural students reporting greater access to smoking tobacco, chewing tobacco, and steroids, and urban students reporting greater access to alcohol, marijuana, cocaine, inhalants, ecstasy, methamphetamine, hallucinogens, and prescription drugs. Rural high school students reported higher access to alcohol, smoking tobacco, chewing tobacco, and steroids, with urban students reporting higher access to marijuana, cocaine, inhalants, ecstasy, and hallucinogens. Perceptions of ease of access more than doubled for each substance in both geographies between middle and high school. Conclusions In summary, the current study found multiple and fairly consistent differences between rural and urban

Structure-activity relationships for hallucinogenic N,N-dialkyltryptamines: photoelectron spectra and serotonin receptor affinities of methylthio and methylenedioxy derivatives

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

Kline, T.B.; Benington, F.; Morin, R.D.

1982-11-01

Serotonin receptor affinity and photelectron spectral data were obtained on a number of substituted N,N-dimethyltryptamines. Evidence is presented that electron-donating substituents in the 5-position lead to enhanced behavioral disruption activity and serotonin receptor affinity as compared to unsubstituted N,N-dimethyltryptamine and analogues substituted in the 4- or 6-position. Some correlation was found between ionization potentials and behavioral activity, which may have implications concerning the mechanism of receptor binding.

Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches Induced by a Serotonergic Hallucinogen in Mice

PubMed Central

Benvenga, Mark J.; Chaney, Stephen F.; Baez, Melvyn; Britton, Thomas C.; Hornback, William J.; Monn, James A.; Marek, Gerard J.

2018-01-01

There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT) mice were administered (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and observed for head twitch activity. DOI failed to produce significant head twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM) CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice. Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor potentiator CBiPES was able to attenuate the increase in the HTR produced by LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are consistent with the hypothesis that that DOI-induced head twitches are modulated by mGlu2 receptor activation. These results also are in keeping with a critical autoreceptor function for mGlu2 receptors in the prefrontal cortex with differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2 receptor KO mice). The robust attenuation of DOI-induced head twitches in the mGlu2 receptor KO mice appears to reflect the critical role of glutamate in ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future experiments with inducible knockouts for the mGlu2 receptor and/or selective mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in understanding glutamatergic modulation of prefrontal cortical 5-HT2A receptor function. PMID:29599719

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.

Availability of websites offering to sell psilocybin spores and psilocybin.

PubMed

Lott, Jason P; Marlowe, Douglas B; Forman, Robert F

2009-09-01

This study assesses the availability of websites offering to sell psilocybin spores and psilocybin, a powerful hallucinogen contained in Psilocybe mushrooms. Over a 25-month period beginning in March 2003, eight searches were conducted in Google using the term "psilocybin spores." In each search the first 100 nonsponsored links obtained were scored by two independent raters according to standardized criteria to determine whether they offered to sell psilocybin or psilocybin spores. No attempts were made to procure the products offered for sale in order to ascertain whether the marketed psilocybin was in fact "genuine" or "counterfeit." Of the 800 links examined, 58% led to websites offering to sell psilocybin spores. Additionally, evidence that whole Psilocybe mushrooms are offered for sale online was obtained. Psilocybin and psilocybin spores were found to be widely available for sale over the Internet. Online purchase of psilocybin may facilitate illicit use of this potent psychoactive substance. Additional studies are needed to assess whether websites offering to sell psilocybin and psilocybin spores actually deliver their products as advertised.

Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors.

PubMed

Carter, Olivia L; Burr, David C; Pettigrew, John D; Wallis, Guy M; Hasler, Felix; Vollenweider, Franz X

2005-10-01

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

The drug use behaviour of cocaine users.

PubMed

Moosburger, R; Plant, A J; Pierce, J P

1990-01-01

We interviewed 50 current cocaine users with the aim of providing insights into cocaine use in Sydney. The study sample was obtained by one researcher using a chain referral technique. Appointments were made for interview and the interview aimed to determine the quantity, frequency, pattern and circumstances of drug use in the respondents. The study sample included people with a wide range of incomes and occupations; all but one person were employed. Extensive current drug use was reported; 78% smoked tobacco, 98% drank alcohol with 36% having more than two drinks per day, 96% used marijuana with 40% smoking marijuana at least 5 times per week, 65% used amphetamines, 36% used hallucinogens and 10% used heroin. Ten per cent were unable to name one health risk of cocaine. When asked about the image of a cocaine user, 42% thought of a rock star, film industry worker or someone involved in the arts and entertainment world. The information obtained from a study such as this provides important data for targeting of people in anti-drug campaigns.

Substance Use among a Sample of Healthcare Workers in Kenya: A Cross-Sectional Study.

PubMed

Mokaya, Aggrey G; Mutiso, Victoria; Musau, Abednego; Tele, Albert; Kombe, Yeri; Ng'ang'a, Zipporah; Frank, Erica; Ndetei, David M; Clair, Veronic

2016-01-01

This study describes reported substance use among Kenyan healthcare workers (HCWs), as it has implications for HCWs' health, productivity, and their ability and likelihood to intervene on substance use. The Alcohol Smoking and Substance Involvement Screening Test (ASSIST) was administered to a convenience sample of HCWs (n = 206) in 15 health facilities. Reported lifetime use was 35.8% for alcohol, 23.5% for tobacco, 9.3% for cannabis, 9.3% for sedatives, 8.8% for cocaine, 6.4% for amphetamine-like stimulants, 5.4% for hallucinogens, 3.4% for inhalants, and 3.9% for opioids. Tobacco and alcohol were also the two most commonly used substances in the previous three months. Male gender and other substance use were key predictors of both lifetime and previous three months' use rates. HCWs' substance use rates appear generally higher than those seen in the general population in Kenya, though lower than those reported among many HCWs globally. This pattern of use has implications for both HCWs and their clients.

Using in vitro models for expression profiling studies on ethanol and drugs of abuse.

PubMed

Thibault, Christelle; Hassan, Sajida; Miles, Michael

2005-03-01

The use of expression profiling with microarrays offers great potential for studying the mechanisms of action of drugs of abuse. Studies with the intact nervous system seem likely to be most relevant to understanding the mechanisms of drug abuse-related behaviours. However, the use of expression profiling with in vitro culture models offers significant advantages for identifying details of cellular signalling actions and toxicity for drugs of abuse. This study discusses general issues of the use of microarrays and cell culture models for studies on drugs of abuse. Specific results from existing studies are also discussed, providing clear examples of relevance for in vitro studies on ethanol, nicotine, opiates, cannabinoids and hallucinogens such as LSD. In addition to providing details on signalling mechanisms relevant to the neurobiology of drugs of abuse, microarray studies on a variety of cell culture systems have also provided important information on mechanisms of cellular/organ toxicity with drugs of abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo and in vitro models offer the potential for novel mechanistic rigor and physiological relevance.

SPICE/K2 Synthetic Marijuana-Induced Toxic Hepatitis Treated with N-Acetylcysteine

PubMed Central

Sheikh, Israr A.; Lukšič, Miha; Ferstenberg, Richard; Culpepper-Morgan, Joan A.

2014-01-01

Patient: Male, 45 Final Diagnosis: Spice/K2 induced liver injury Symptoms: Lethargy • somnolence • fatigue Medication: N-acetylcysteine Clinical Procedure: — Specialty: Gastroenterology Objective: Rare disease Background: Spice/K2 is one of several street names for synthetic marijuana. These hallucinogens are increasingly sold over the internet and in “head” shops. They are usually household herbs that are sprayed with chemicals that become centrally active compounds when burned together and inhaled by smoking. Case Report: We present a case of a 45-year-old male substance abuser who was admitted with evidence of hepatocellular necrosis and worsening liver failure. Tests for acetaminophen were negative, as were tests for alcohol. The patient was empirically treated with N-acetylcysteine. Hepatocellular damage was abated and the patient made a full recovery. Upon regaining consciousness, the patient admitted to smoking Spice/K2. Other toxicities have been reported with synthetic marijuana use, but not liver toxicity. Conclusions: Physicians need to have a high index of suspicion for unknown hepatotoxins in substance abusers. N-acetylcysteine can be given if there is no contraindication. PMID:25548903

The neuropsychology of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues.

PubMed

Coulston, Carissa M; Perdices, Michael; Tennant, Christopher C

2007-11-01

Research on the neuropsychology of substance use in schizophrenia has been steadily growing over the past decade. However, significant gaps remain in the knowledge of individual substances and their relationship to cognition in the schizophrenia spectrum disorders. Approximately 65 studies to date have directly examined this relationship. Of these, approximately 20 have focused on nicotine, 15 on alcohol, 10 on cocaine, three on stimulants/hallucinogens, one on benzodiazepines, 10 on polydrug abuse, and seven on cannabis. Research on cannabis is especially lacking, given that worldwide it is the most commonly used illicit drug in schizophrenia, is used at higher rates in schizophrenia than in the general population, and makes its own unique contribution to the onset and prognosis of schizophrenia. In the present paper an overview of the neuropsychology literature on substance use in schizophrenia is presented, with special emphasis on cannabis. This incorporates a discussion of the methodological limitations inherent in these studies, and range of potential confounding variables that were not considered or controlled, providing directions for future research into the cognitive correlates of cannabis and other substance use in schizophrenia.

Illicit Drug Use and Treatment in South Africa

PubMed Central

Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D.; Phaswana-Mafuya, Nancy

2008-01-01

This review synthesizes available epidemiological data on current drug use and substance abuse treatment admissions in south africa since 1994, and how changes in the political, economic and social structures within south africa both before and after apartheid make the country more vulnerable to drug use. based on national surveys current use of cannabis ranged among adolescents from 2% to 9% and among adults 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%) and hallucinogens (0.1%). The primary illicit substance at admission to South African drug treatment centers was cannabis 16.9%, methamphetamine (Tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC 2.6%. An increase in substance abuse treatment admissions has occurred. While the prevalence of illicit drug use in South Africa is relatively low compared to the USA and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review. PMID:21039113

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

Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression.

PubMed

Cameron, Lindsay P; Benson, Charlie J; Dunlap, Lee E; Olson, David E

2018-04-24

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N, N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.

Innovative Recruitment Using Online Networks: Lessons Learned From an Online Study of Alcohol and Other Drug Use Utilizing a Web-Based, Respondent-Driven Sampling (webRDS) Strategy

PubMed Central

Bauermeister, José A.; Zimmerman, Marc A.; Johns, Michelle M.; Glowacki, Pietreck; Stoddard, Sarah; Volz, Erik

2012-01-01

Objective: We used a web version of Respondent-Driven Sampling (webRDS) to recruit a sample of young adults (ages 18–24) and examined whether this strategy would result in alcohol and other drug (AOD) prevalence estimates comparable to national estimates (National Survey on Drug Use and Health [NSDUH]). Method: We recruited 22 initial participants (seeds) via Facebook to complete a web survey examining AOD risk correlates. Sequential, incentivized recruitment continued until our desired sample size was achieved. After correcting for webRDS clustering effects, we contrasted our AOD prevalence estimates (past 30 days) to NSDUH estimates by comparing the 95% confidence intervals of prevalence estimates. Results: We found comparable AOD prevalence estimates between our sample and NSDUH for the past 30 days for alcohol, marijuana, cocaine, Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), and hallucinogens. Cigarette use was lower than NSDUH estimates. Conclusions: WebRDS may be a suitable strategy to recruit young adults online. We discuss the unique strengths and challenges that may be encountered by public health researchers using webRDS methods. PMID:22846248

Substance Use among a Sample of Healthcare Workers in Kenya: A Cross-Sectional Study

PubMed Central

Mokaya, Aggrey G.; Mutiso, Victoria; Musau, Abednego; Tele, Albert; Kombe, Yeri; Ng’ang’a, Zipporah; Frank, Erica; Ndetei, David M.; Clair, Veronic

2016-01-01

ABSTRACT This study describes reported substance use among Kenyan healthcare workers (HCWs), as it has implications for HCWs’ health, productivity, and their ability and likelihood to intervene on substance use. The Alcohol Smoking and Substance Involvement Screening Test (ASSIST) was administered to a convenience sample of HCWs (n = 206) in 15 health facilities. Reported lifetime use was 35.8% for alcohol, 23.5% for tobacco, 9.3% for cannabis, 9.3% for sedatives, 8.8% for cocaine, 6.4% for amphetamine-like stimulants, 5.4% for hallucinogens, 3.4% for inhalants, and 3.9% for opioids. Tobacco and alcohol were also the two most commonly used substances in the previous three months. Male gender and other substance use were key predictors of both lifetime and previous three months’ use rates. HCWs’ substance use rates appear generally higher than those seen in the general population in Kenya, though lower than those reported among many HCWs globally. This pattern of use has implications for both HCWs and their clients. PMID:27485987

Innovative recruitment using online networks: lessons learned from an online study of alcohol and other drug use utilizing a web-based, respondent-driven sampling (webRDS) strategy.

PubMed

Bauermeister, José A; Zimmerman, Marc A; Johns, Michelle M; Glowacki, Pietreck; Stoddard, Sarah; Volz, Erik

2012-09-01

We used a web version of Respondent-Driven Sampling (webRDS) to recruit a sample of young adults (ages 18-24) and examined whether this strategy would result in alcohol and other drug (AOD) prevalence estimates comparable to national estimates (National Survey on Drug Use and Health [NSDUH]). We recruited 22 initial participants (seeds) via Facebook to complete a web survey examining AOD risk correlates. Sequential, incentivized recruitment continued until our desired sample size was achieved. After correcting for webRDS clustering effects, we contrasted our AOD prevalence estimates (past 30 days) to NSDUH estimates by comparing the 95% confidence intervals of prevalence estimates. We found comparable AOD prevalence estimates between our sample and NSDUH for the past 30 days for alcohol, marijuana, cocaine, Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), and hallucinogens. Cigarette use was lower than NSDUH estimates. WebRDS may be a suitable strategy to recruit young adults online. We discuss the unique strengths and challenges that may be encountered by public health researchers using webRDS methods.

Benzylpiperazine: "A messy drug".

PubMed

Katz, D P; Deruiter, J; Bhattacharya, D; Ahuja, M; Bhattacharya, S; Clark, C R; Suppiramaniam, V; Dhanasekaran, M

2016-07-01

Designer drugs are synthetic structural analogues/congeners of controlled substances with slightly modified chemical structures intended to mimic the pharmacological effects of known drugs of abuse so as to evade drug classification. Benzylpiperazine (BZP), a piperazine derivative, elevates synaptic dopamine and serotonin levels producing stimulatory and hallucinogenic effects, respectively, similar to the well-known drug of abuse, methylenedioxymethamphetamine (MDMA). Furthermore, BZP augments the release of norepinephrine by inhibiting presynaptic autoreceptors, therefore, BZP is a "messy drug" due to its multifaceted regulation of synaptic monoamine neurotransmitters. Initially, pharmaceutical companies used BZP as a therapeutic drug for the treatment of various disease states, but due to its contraindications and abuse potential it was withdrawn from the market. BZP imparts predominately sympathomimetic effects accompanied by serious cardiovascular implications. Addictive properties of BZP include behavioral sensitization, cross sensitization, conditioned place preference and repeated self-administration. Additional testing of piperazine derived drugs is needed due to a scarcity of toxicological data and widely abuse worldwide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ibogaine-associated cardiac arrest and death: case report and review of the literature.

PubMed

Meisner, Jessica A; Wilcox, Susan R; Richards, Jeremy B

2016-04-01

A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine's clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine.

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.

Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of hallucinogenic drugs in hair of psychedelic plants and mushrooms consumers.

PubMed

Pichini, Simona; Marchei, Emilia; García-Algar, Oscar; Gomez, Arelis; Di Giovannandrea, Rita; Pacifici, Roberta

2014-11-01

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of mescaline, N,N-dimethyltryptamine, psilocin, psilocybin, salvinorin A in hair of consumers of psychedelic vegetal material such peyote or trichocereus cacti, psilocybe mushrooms, Salvia divinorum or psychedelic beverage ayahuasca. After hair washing with methyl alcohol and diethyl ether and subsequent addition of mescaline-d9 and 3,4-methylenedioxypropylamphetamine as internal standards, hair samples were treated with 250μl VMA-T M3 reagent for 1h at 100°C. After cooling, 100μl M3 extract were diluted with 400μl water and a volume of 10μl was injected into chromatographic system. Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.03-0.05ng/mg depending on analyte under investigation) to 10ng/mg hair, with an intra- and inter-assay imprecision and inaccuracy always less than 15% and an analytical recovery between 79.6% and 97.4%, depending on the considered analyte. Using the validated method, mescaline was found in concentration range of 0.08-0.13ng/mg in hair of peyote smokers, 3.2ng salvinorin A per mg hair were determined in hair from a S. divinorum smoker, 5.6ng N,N-dimethyltryptamine per mg hair from an ayahuasca user and finally 0.8ng psilocybin per ng hair of a psilocybe consumer. Copyright © 2014 Elsevier B.V. All rights reserved.

Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers from 2005 to 2015.

PubMed

Heise, C William; Brooks, Daniel E

2017-09-01

Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in β-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia. All human exposure calls reported to the American Association of Poison Controls Centers' (AAPCC) National Poison Data System (NPDS) between September 1, 2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant derived ayahuasca-related product codes. Abstracted data included the following: case age and gender, exposure reason, exposure route, clinical manifestations, treatments given, medical outcomes and fatality. Five hundred and thirty-eight exposures to ayahuasca botanical products were reported. The majority of the calls to poison control centers came from healthcare facilities (83%). The most common route of exposure was ingestion. Most cases were men (437, 81%, 95% CI 77.7% - 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute. Three hundred thirty-seven (63%) were reported to have a major or moderate clinical effect. The most common clinical manifestations reported were hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%), mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%). There were 28 cases in the series who required endotracheal intubation (5

The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors.

PubMed

Winter, J C; Filipink, R A; Timineri, D; Helsley, S E; Rabin, R A

2000-01-01

Stimulus control was established in rats trained to discriminate either 5-methoxy-N,N-dimethyltryptamine (3 mg/kg) or (-)-2,5-dimethoxy-4-methylamphetamine (0.56 mg/kg) from saline. Tests of antagonism of stimulus control were conducted using the 5-HT1A antagonists (+/-)-pindolol and WAY-100635, and the 5-HT2 receptor antagonist pirenperone. In rats trained with 5-MeO-DMT, pindolol and WAY-100635 both produced a significant degree of antagonism of stimulus control, but pirenperone was much less effective. Likewise, the full generalization of 5-MeO-DMT to the selective 5-HT1A agonist [+/-]-8-hydroxy-dipropylaminotetralin was blocked by WAY-100635, but unaffected by pirenperone. In contrast, the partial generalization of 5-MeO-DMT to the 5-HT2 agonist DOM was completely antagonized by pirenperone, but was unaffected by WAY-100635. Similarly, in rats trained with (-)-DOM, pirenperone completely blocked stimulus control, but WAY-100635 was inactive. The results obtained in rats trained with (-)-DOM and tested with 5-MeO-DMT were more complex. Although the intraperitoneal route had been used for both training drugs, a significant degree of generalization of (-)-DOM to 5-MeO-DMT was seen only when the latter drug was administered subcutaneously. Furthermore, when the previously effective dose of pirenperone was given in combination with 5-MeO-DMT (s.c.), complete suppression of responding resulted. However, the combination of pirenperone and WAY-100635 given prior to 5-MeO-DMT restored responding in (-)-DOM-trained rats, and provided evidence of antagonism of the partial substitution of 5-MeO-DMT for (-)-DOM. The present data indicate that 5-MeO-DMT-induced stimulus control is mediated primarily by interactions with 5-HT1A receptors. In addition, however, the present findings suggest that 5-MeO-DMT induces a compound stimulus that includes an element mediated by interactions with a 5-HT2 receptors. The latter component is not essential for 5-MeO-DMT-induced stimulus control, but is revealed in animals tested or trained with a 5-HT2-selective agonist such as (-)-DOM. Based upon the present data, we conclude that 5-MeO-DMT differs from DOM with respect to the serotonergic element that mediates stimulus control in the rat, but that it shares with DOM a functionally significant interaction with 5-HT2 receptors.

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

PubMed Central

Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

2011-01-01

Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

PubMed

Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

2012-06-01

Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks.

PubMed

Kavenská, Veronika; Simonová, Hana

2015-01-01

Ayahuasca continues to attract tourists to South America, where there has been a growth in the number of centers offering hallucinogenic ayahuasca experiences. The aims of this study were to (1) discover the reasons foreigners seek this type of experience; (2) define what an ayahuasca experience entails; (3) discover subjective perceptions of ayahuasca's benefits and risks; and (4) describe personality styles of participants using the personality questionnaire (PSSI). Participants (N=77) were persons who had travelled to South America to use ayahuasca. Among the most frequent motivations were curiosity, desire to treat mental health problems, need for self-knowledge, interest in psychedelic medicine, spiritual development, and finding direction in life. Frequently mentioned benefits included self-knowledge, change in the way one relates to oneself, spiritual development, improved interpersonal relations, overcoming mental and physical problems, and gaining a new perspective on life. Stated potential risks included lack of trust in the shaman or organizer, inaccurate information provided by the shaman or organizer, and exposure to dangerous situations. PSSI results showed that people using ayahuasca scored significantly above the norm on the scales of intuition, optimism, ambition, charm, and helpfulness and significantly lower on the scales of distrust and quietness.

Problem drinking and the dimension of involvement with drugs: a Guttman scalogram analysis of adolescent drug use.

PubMed Central

Donovan, J E; Jessor, R

1983-01-01

Analyses of data from two nationwide surveys of high school students, one carried out in 1974 and the other in 1978, suggest that problem drinking may be seen as yet another step along an underlying dimension of involvement with both licit and illicit drugs. The dimension of involvement with drugs consists of the following levels: nonuse of alcohol or illicit drugs; nonproblem use of alcohol; marijuana use; problem drinking; use of pills (amphetamines, barbiturates, hallucinogenic drugs); and the use of "hard drugs" such as cocaine or heroin. The dimension possesses excellent Guttman-scale properties in both national samples as well as in subsamples differing in gender and ethnic background. The ordering of the levels of involvement was confirmed by the ordering of the alcohol-drug involvement groups based on their mean scores on measures of psychosocial proneness for involvement in problem behavior. The excessive use of a licit drug, i.e., problem drinking, appears to indicate greater involvement in drug use than does the use of an illicit drug, marijuana. This finding points to the importance of distinguishing between use and problem use of drugs in efforts to understand adolescent drug involvement. PMID:6837819

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

PubMed

Nunes, Amanda A; Dos Santos, Rafael G; Osório, Flávia L; Sanches, Rafael F; Crippa, José Alexandre S; Hallak, Jaime E C

2016-01-01

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members.

PubMed

Santos, R G; Landeira-Fernandez, J; Strassman, R J; Motta, V; Cruz, A P M

2007-07-25

The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

Plants and the central nervous system.

PubMed

Carlini, E A

2003-06-01

This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide.

PubMed

Mucke, Hermann A M

2016-07-08

Among the psychedelic drugs that enjoyed a period of popularity in psychiatric research during the 1950s and 1960s, lysergic acid diethylamide (LSD) is the most prominent one. Psychiatrists of that time had seen LSD not only as a tool for psychotherapy but also as a potential therapeutic for anxiety, depression, alcohol abuse, autism, and even schizophrenia. When it became a quasi-religious epitome of the Hippie counterculture in the mid 1960s, and cases of what we now call hallucinogen persisting perception disorder and acute psychotic "flashbacks" mounted, authorities moved to make LSD illegal. Although research was never actually forbidden, the field almost completely dried out until the early 2010s. Using today's tools of molecular pharmacology, functional imaging, and neuronal network theory, neuropsychiatry is now resurrecting LSD research-with implications that leave us with many medical and ethical questions. Few people are aware that this is a repurposed compound, originally developed in an effort to synthesize a new analeptic. On top of all potential LSD might have in psychiatry, it also serves as a reminder of the unexpected potential that discarded early-stage compounds can have.

Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

PubMed

Hu, Qi-Di; Xu, Ling-Li; Gong, Yan; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun; Zhang, Zhe; Mao, Wei; Zhou, Yu-Sheng; Li, Qin-Bo; Yuan, Jian-Shu

2018-01-19

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

Prevalence and pattern of substance use among undergraduates in a Nigerian University.

PubMed

Adelekan, M L; Abiodun, O A; Obayan, A O; Oni, G; Ogunremi, O O

1992-02-01

The prevalence and pattern of substance use was investigated among undergraduate students of the University of Ilorin, Kwara State, Nigeria in June 1988. Six hundred and forty-nine students completed a 117-item self-report questionnaire 636 of which were analysed. Mean age and S.D. of respondents was 23 +/- 3.7 years; 69% were males. The most commonly used substances with their 'lifetime' prevalence rates were as follows: salicylate analgesics, 95.2%; alcohol, 77%; stimulants, 69.2%; antibiotics, 63.3%; hypno-sedatives, 49.4% and cigarettes, 37.4%. The corresponding 'current use' rates were relatively lower. Low use was recorded for cannabis, organic solvents, hallucinogens, cocaine and narcotic analgesics. Majority of the 'current users' use the substances on an occasional basis except for cigarettes where more than half reported weekly or daily use. Males were significantly more of 'current' users of cigarettes and alcohol while females tend to use stimulants more. The use of most of the substances started in primary school. The need for a comprehensive demand-reduction programme in Nigeria based on this and other local findings was advocated. Continuous monitoring, particularly of hard drug use, appears imperative.