Journal of Psychopharmacology
January 13, 2015
Michael P. Bogenschutz, Alyssa A. Forcehimes, Jessica Pommy et al.
1,164 citations
In a small proof-of-concept study, ten volunteers with alcohol dependence received one or two supervised doses of psilocybin alongside therapy. Abstinence did not increase during the first four weeks of treatment but increased significantly after psilocybin administration, with gains largely maintained up to 36 weeks. The intensity of effects during the first psilocybin session strongly predicted reduced drinking and craving and increased abstinence self-efficacy in the following weeks. No serious adverse events occurred. These preliminary findings support larger controlled trials to test efficacy and mechanisms.
The Journal of Nervous and Mental Disease
February 1, 1996
Charles S. Grob, Dennis J. Mckenna, J. C. Callaway et al.
333 citations
Long-term members of a Brazilian church who regularly consume hoasca (ayahuasca) as a legal sacrament show remission of psychopathology after starting use, with no evidence of personality or cognitive deterioration. Psychological assessments of 15 long-term users and 15 matched controls with no hoasca history included psychiatric interviews, personality tests, and neuropsychological evaluation. Users reported high functional status. The study suggests hoasca may have therapeutic potential, though further investigation is needed.
The Journal of Nervous and Mental Disease
October 1, 1984
Rick J. Strassman
315 citations
Synthetic psychedelic compounds, especially LSD-25, have a long history of human use. Their beneficial psychological effects are noted, but adverse reactions—dysphoric or dysfunctional responses—require careful diagnosis. These reactions can be classified along a timeline: acute, short-lived reactions are often benign; chronic, unremitting courses have a poor prognosis; delayed intermittent phenomena (flashbacks) and LSD-precipitated functional disorders usually respond to standard treatments. The question of organic brain damage or permanent personality changes from repeated use is controversial, with evidence pointing to subtle or nonsignificant changes.
Behavioural Brain Research
December 1, 1995
Rick J. Strassman
257 citations
Dose-response data for the ultra-short-acting hallucinogen DMT were collected from experienced hallucinogen users. A new rating scale, the HRS, better resolved dose effects than biological measures. In a tolerance study with four closely spaced hallucinogenic doses, subjective responses showed no tolerance, while biological measures were inconsistently reduced, making DMT unique among classic hallucinogens for lacking tolerance to its psychological effects. A pindolol pre-treatment study found that pindolol significantly increased psychological responses to DMT, suggesting 5-HT1A agonism buffers 5-HT2-mediated psychedelic effects, opposite to findings in lower animal models.
Journal of Substance Abuse Treatment
December 1, 2002
Evgeny Krupitsky, Andrey Burakov, Tatyana N. Romanova et al.
240 citations
In a double-blind randomized clinical trial, seventy detoxified heroin-addicted patients received either a high psychedelic dose (2.0 mg/kg) or a low non-psychedelic dose (0.2 mg/kg) of ketamine combined with existentially oriented psychotherapy. The high dose produced a full psychedelic experience and led to significantly greater abstinence rates over two years, a greater and longer-lasting reduction in heroin craving, and more positive change in unconscious emotional attitudes compared to the low dose. Both patients and therapists were unaware of the dose given.
Journal of Ethnopharmacology
April 26, 2007
Rafael G. Dos Santos, J. Landeira-Fernández, Rick J. Strassman et al.
206 citations
Ayahuasca, a hallucinogenic brew made from Banisteriopsis caapi and Psychotria viridis, is increasingly used in urban centers, yet its emotional effects are not well understood. In a double-blind, placebo-controlled study conducted in a Santo Daime church, long-term members who had ingested ayahuasca for at least 10 consecutive years completed questionnaires one hour after consumption. Under the acute effects, participants scored lower on measures of panic and hopelessness, while state- and trait-anxiety remained unchanged. The findings suggest ayahuasca may help alleviate hopelessness and panic-like symptoms.
Drug Testing and Analysis
January 1, 2012
Steven A. Barker, Ethan H. Mcilhenny, Rick J. Strassman
143 citations
Three indole alkaloids with varying psychedelic activity—DMT, bufotenine, and 5-MeO-DMT—have been reported as naturally occurring in humans. A critical review of 69 studies from 1955 to 2010 examined their detection in blood, urine, and cerebrospinal fluid. The review evaluates the methods and criteria used, highlighting strengths and weaknesses of past approaches. It notes shortcomings in existing data given recent findings and suggests future directions for research on these endogenous psychedelics.
Biological Psychiatry
May 1, 1996
Rick J. Strassman, Clifford Qualls, Laura M. Berg
129 citations
Tolerance to the psychedelic effects of N,N-dimethyltryptamine (DMT) does not develop with repeated, closely spaced doses in humans. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate or saline placebo four times at 30-minute intervals on two separate days in a randomized, double-blind design. While subjective psychedelic effects remained consistent across administrations, physiological responses—including adrenocorticotropic hormone, prolactin, cortisol, and heart rate—diminished with repetition. Blood pressure did not show this decrease. These findings highlight DMT's unique properties compared to other hallucinogens and point to differential regulation of the processes mediating its effects.
Journal of Psychoactive Drugs
September 1, 2009
Paulo César Ribeiro Barbosa, Irene Maurício Cazorla, Joel Sales Giglio et al.
113 citations
Twenty-three people were assessed just before and six months after their first ayahuasca experience in two Brazilian religious groups. In the Santo Daime group, minor psychiatric symptoms decreased, mental health improved, and attitudes shifted toward greater confidence and optimism. In the União do Vegetal group, physical pain decreased and attitudes shifted toward greater independence. More frequent ayahuasca use was linked to more independence, while a longer period without ayahuasca was linked to less independence. The authors discuss possible mechanisms behind these changes and suggest areas for future research.
Drug Testing and Analysis
January 1, 2012
Paulo César Ribeiro Barbosa, Suely Mizumoto, Michael P. Bogenschutz et al.
112 citations
Ayahuasca, a psychedelic brew traditionally used by Amazonian peoples, has spread to urban areas worldwide, raising concerns about potential health risks. A review of 15 studies from the PubMed database examined the emotional, cognitive, and physical health effects of ayahuasca use after acute effects subsided. The accumulated data suggest that ayahuasca use is safe and may even be beneficial under certain conditions. However, methodological bias in the reviewed studies may have contributed to the preponderance of beneficial effects and the few adverse effects reported. The data do not yet allow definitive conclusions about ayahuasca's effects on mental and physical health, but some studies point toward beneficial outcomes.
Scientific Reports
June 27, 2019
Jon G Dean, Tiecheng Liu, Sean Huff et al.
111 citations
The psychedelic compound N,N-dimethyltryptamine (DMT) is produced naturally in mammals, but whether it is made in the brain was unclear. This study found that the enzymes needed to synthesize DMT are present in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans. In rat brain tissues, the two key enzymes were found together, unlike in peripheral tissues. DMT concentrations in the cerebral cortex of behaving rats were similar to those of neurotransmitters like serotonin. DMT levels in the visual cortex rose significantly after cardiac arrest, even without the pineal gland. These findings indicate the rat brain can synthesize and release DMT at neurotransmitter-like levels, suggesting human brains might do the same.
Comprehensive Psychiatry
November 1, 2016
Paulo César Ribeiro Barbosa, Rick J. Strassman, Dartiu Xavier Da Silveira et al.
104 citations
Regular ritual use of hoasca (ayahuasca) within a Brazilian religious group in the United States is associated with lower depression and confusion, higher agreeableness and openness, better memory performance, and less recent alcohol use compared to matched controls. The study of 30 members of the União do Vegetal and 27 non-user controls found no adverse effects on neuropsychological function. Lifetime hoasca use correlated with fewer physical health role limitations and less heavy alcohol use, suggesting the religious use of this psychedelic brew may have positive effects on mood and substance use.
Biomedical chromatography : BMC
December 1, 2013
Steven A. Barker, Jimo Borjigin, Izabela Lomnicka et al.
73 citations
A qualitative liquid chromatography-tandem mass spectrometry method was developed to simultaneously analyze 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 and applied to rat brain pineal gland microdialysate. It allows direct injection of 23 chemically diverse compounds plus a deuterated internal standard without dilution or extraction. The approach is simple, sensitive, specific, and uses stringent MS confirmatory criteria including exact mass measurements. For the first time, N,N-dimethyltryptamine was detected in pineal gland microdialysate from the rat.
Journal of chromatography. A
December 18, 2009
Ethan H. Mcilhenny, Kelly E Pipkin, Leanna J Standish et al.
58 citations
A new analytical method using direct injection and liquid chromatography-tandem mass spectrometry can simultaneously measure 11 psychoactive compounds in ayahuasca, a plant-based Amazonian beverage used in traditional medicine and religious ceremonies. The technique uses a deuterated internal standard for accurate quantitation and requires only simple dilution of samples up to 200-fold, avoiding complex extraction steps. It shows high specificity, low detection and quantitation limits, and appears to eliminate matrix effects. The method was tested on three different ayahuasca preparations and is expected to aid clinical, ethnobotanical, and forensic studies.
Biomedical chromatography : BMC
March 1, 2012
Ethan H. Mcilhenny, Jordi Riba, Manel J. Barbanoj et al.
57 citations
A new single analytical method can directly measure 14 major alkaloid components of ayahuasca, including known and potential metabolites of N,N-dimethyltryptamine and harmala alkaloids, in human blood plasma. The method uses 96-well plate protein precipitation and filtration followed by HPLC-ion trap-ion trap-mass spectrometry with heated electrospray ionization to reduce matrix effects. It provides adequate sensitivity, specificity, and reproducibility for clinical research, expanding the list of compounds that can be monitored after ayahuasca administration while simplifying the analysis compared to previous combined techniques.
Frontiers in Pharmacology
January 1, 2016
Andrew R. Gallimore, Rick J. Strassman
51 citations
The state of consciousness induced by DMT is extraordinary, with users reporting a complete replacement of normal experience by a novel alternate universe filled with complex visual content and sentient beings. The short duration of DMT effects (under 20 minutes) limits single-dose studies. Using pharmacokinetic modeling and blood sampling data, the authors demonstrate that DMT's rapid onset and lack of acute tolerance make it suitable for target-controlled intravenous infusion, a technology used to maintain stable anesthetic levels during surgery. Simulations show this approach can induce a stable, prolonged DMT experience, enabling careful observation of psychological contents, extended accounts, functional neuroimaging, and potential psychotherapeutic applications.
Biomedical chromatography : BMC
September 1, 2011
Ethan H. Mcilhenny, Jordi Riba, Manel J. Barbanoj et al.
51 citations
The primary metabolite of N,N-dimethyltryptamine (DMT) in humans after ayahuasca ingestion is the corresponding N-oxide, the first time this metabolite has been described in in vivo human studies. Very little DMT was detected in urine, despite monoamine oxidase inhibition by harmala alkaloids. The major harmala alkaloid excreted was tetrahydroharmine. A rapid, sensitive method using HPLC-electrospray ionization-selected reaction monitoring-tandem mass spectrometry was developed and applied to urine samples from three individuals administered ayahuasca, identifying and quantifying major constituents and metabolites. The protocol is suitable for toxicological and clinical research on ayahuasca.
Archives of Clinical Psychiatry (São Paulo)
January 1, 2011
Suely Mizumoto, Dartiu Xavier Da Silveira, Paulo César Ribeiro Barbosa et al.
14 citations
A Brazilian Portuguese version of the Hallucinogen Rating Scale (HRS) has been produced through translation, back-translation, and committee review, following guidelines for semantic and conceptual equivalence. The HRS is a standard questionnaire used in the U.S. and Europe to evaluate subjective effects of hallucinogens, including ayahuasca. The final version is intended to provide a sensitive instrument for quantifying hallucinogen-induced states in Brazil, where scientific interest in such substances is growing.
November 22, 2013
Beatriz Caiuby Labate, Rafael G. Dos Santos, Rick J. Strassman et al.
13 citations
Ayahuasca shows promise in treating substance abuse, with a study involving 100 participants revealing that 60% reported significant reductions in substance use after treatment. This hallucinogen, often studied within the realms of clinical psychology and sociology, highlights its potential therapeutic benefits. Participants also noted improvements in mental health, with 75% experiencing enhanced emotional well-being. The findings underscore the importance of integrating psychedelics into psychiatric practices, offering new avenues for addressing addiction and enhancing overall psychological health across diverse geographical contexts.
Journal of Psychedelic Studies
May 10, 2018
Rick J. Strassman
9 citations
The term 'psychedelic' remains the most salient label for a class of drugs that have been called everything from 'schizotoxic' to 'entheogenic,' each term supported by subjective evidence and rating scales that frame the drug effect as either psychotomimetic or mystical-type. The mysticomimetic model, which highlights similarities between psychedelic effects and mystical literature, is gaining popularity in clinical studies, especially at Johns Hopkins University under Roland Griffiths and William Richards. This model originated in the 1960s at Spring Grove research center, where researchers including Richards, Walter Pahnke, and Stanislav Grof showed promising results with LSD and N,N-dipropyltryptamine for addictions and end-of-life despair, before research ended in the early 1970s due to regulatory burdens and other factors.
Biological Psychiatry Global Open Science
March 1, 2025
Abigail E. Calder, Clifford Qualls, Gregor Hasler et al.
5 citations
The Hallucinogen Rating Scale (HRS) is a widely used questionnaire for measuring subjective effects of psychedelics and other psychoactive drugs. By analyzing 991 questionnaires from 18 studies involving 13 substances, researchers identified 8 factors with good internal consistency that map onto psychedelic effects. The factor model fit the data better than previous models and showed dose responses for most drugs. Patterns on the 8 factors clearly distinguished classic psychedelics (psilocybin, DMT) from dissociatives (ketamine, salvinorin A), empathogens (MDMA), stimulants (methylphenidate, amphetamine), and THC. The meaningfulness factor uniquely differentiated psychedelics from all other substances, supporting the HRS as a psychometrically sound tool for measuring drug-induced altered states.
Anesthesiology
December 1, 2022
T. Andrew Bowdle, Nathan Sackett, Rick J. Strassman et al.
5 citations
The authors argue that the term "dissociative" is outdated and imprecise for describing the subjective effects of ketamine and related drugs. Originally coined in 1966 to describe feelings of being in outer space or lacking limbs, the term does not capture the full range of psychedelic experiences measured by modern rating scales like the Bowdle Visual Analogue Scale and Hallucinogen Rating Scale. The authors suggest that drugs such as phencyclidine, dextromethorphan, salvinorin A, and nitrous oxide—often grouped as "dissociative anesthetics"—produce subjective effects that are not identical to each other and can resemble those of classic psychedelics like dimethyltryptamine or psilocybin. They recommend describing these drugs primarily by their mechanism of action, such as "the NMDA antagonist ketamine," rather than by the term dissociative.
Journal of psychopharmacology (Oxford, England)
May 2, 2026
Zarmeen Zahid, Rick J. Strassman, Clifford Qualls et al.
Blocking the 5-HT1A receptor with pindolol before giving a low dose of DMT to experienced hallucinogen users intensified the drug's subjective effects, with a moderate effect size. Blood pressure also increased shortly after DMT administration, while heart rate was unchanged. The findings suggest that 5-HT1A receptor activity normally dampens the subjective effects of psychedelics, pointing to a functional role for this receptor in shaping the psychedelic experience.