Psychological and neuropsychological assessment of regular hoasca users.

BACKGROUND: Hoasca (also called ayahuasca) is a N,N-dimethyltryptamine (DMT) - containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting. METHODS: Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of União do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann-Whitney U, chi-squared and Fisher tests were used to analyze differences between groups. Spearman's association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables. RESULTS: Relative to the control group, the UDV group demonstrated lower scores for depression (p=0.043, r=.27) and confusion (p=0.032, r=.29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits agreeableness (p=0.028, r=.29) and openness (p=0.037, r=.28); higher scores on the quality life domain role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 - SF-36 (p=0.035, r=.28); less recent use of alcohol (p<0.001, φc=.57), greater past use of alcohol to intoxication (p=0.007, φc=.36) and past use of cannabis (p=0.001, φc=.45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test - CVLT (p=0.040, r=.27). Lifetime use of hoasca was positively correlated with role limitations due to physical health (p=0.032, rs=.39) and negatively associated with lifetime heavy alcohol use (p=0.034, OR=0.979). CONCLUSIONS: The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood.

Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain.

N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.

A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience.

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel "alternate universe," often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient "beings." The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

UNLABELLED: Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. TRIAL REGISTRATION: NCT02061293.

Health status of ayahuasca users.

Ayahuasca is a psychedelic brew originally used for magico-religious purposes by Amerindian populations of the western Amazon Basin. Throughout the last four decades, the use of ayahuasca spread towards major cities in all regions of Brazil and abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine- and harmala-alkaloid-containing tea may lead to mental and physical health problems associated typically with drug abuse. To further elucidate the mental and physical health of ayahuasca users, we conducted a literature search in the international medical PubMed database. Inclusion criteria were evaluation of any related effect of ayahuasca use that occurred after the resolution of acute effects of the brew. Fifteen publications were related to emotional, cognitive, and physical health of ayahuasca users. The accumulated data suggest that ayahuasca use is safe and may even be, under certain conditions, beneficial. However, methodological bias of the reviewed studies might have contributed to the preponderance of beneficial effects and to the few adverse effects reported. The data up to now do not appear to allow for definitive conclusions to be drawn on the effects of ayahuasca use on mental and physical health, but some studies point in the direction of beneficial effects. Additional studies are suggested to provide further clarification.

Hallucinogen Rating Scale (HRS) - Versão brasileira: tradução e adaptação transcultural / Hallucinogen Rating Scale (HRS) - A Brazilian version: translation and cross-cultural adaptation

CONTEXTO: Existe um crescente interesse científico pelos efeitos de alucinógenos em geral e, particularmente, pelo uso religioso da bebida psicoativa ayahuasca no Brasil. Todavia, não há no Brasil um instrumento padronizado para avaliar os efeitos de alucinógenos. A Hallucinogen Rating Scale (HRS) é um questionário amplamente usado nos Estados Unidos e na Europa para avaliar os efeitos de diversas substâncias psicoativas, incluindo as alucinógenas. OBJETIVO: Traduzir e adaptar a HRS para o português brasileiro. MÉTODO: A adaptação foi realizada em três etapas: 1) os autores do artigo traduziram a HRS para o português, visando à elaboração de uma versão-síntese inicial; 2) foi feita retrotradução dessa versão para o inglês por dois tradutores independentes; 3) foi elaborada uma versão final em português brasileiro por um comitê de revisão. Esta versão final foi desenvolvida pela comparação entre as traduções iniciais e as retrotraduções, por um processo dialógico com o autor do instrumento. RESULTADOS: Produção da versão final da HRS em português. Observaram-se as diretrizes para equivalência semântica e conceitual entre o português e inglês na descrição de estados subjetivos induzidos por alucinógenos. CONCLUSÃO: Uma versão brasileira da HRS - instrumento largamente empregado em todo o mundo para quantificar os efeitos de psicoativos - fornece um instrumento sensível para a avaliação de efeitos de substâncias alucinógenas no Brasil.

BACKGROUND: There is a growing scientific interest in the effects of hallucinogens in general and the religious use of psychoactive brew ayahuasca in Brazil in particular. However, there is not yet a standard instrument used in Brazil to evaluate the effects of hallucinogens. The Hallucinogen Rating Scale (HRS) is a questionnaire widely used in the U.S. and Europe to evaluate the effects of several psychoactive substances, including hallucinogens. OBJECTIVE: To translate and adapt the HRS to Brazilian Portuguese. METHOD: We followed three steps: 1) the authors of the article translated the HRS into Portuguese, in order to establish an initial version; 2) two independent translators back-translated this version into English; 3) a revision committee produced a final version of the Brazilian Portuguese version. This final version was developed comparing the initial translations and back-translations, through a dialogic process with the author of the instrument. RESULTS: A final Portuguese version of the HRS, following the guidelines for semantic and conceptual equivalence between English and Portuguese to describe hallucinogen-induced subjective states. DISCUSSION: A Brazilian version of the HRS - an instrument widely used throughout the world to quantify effects of psychoactive drugs - provides a sensitive instrument for evaluation of the effects of hallucinogenic substances in Brazil.