Journal of Psychoactive Drugs
June 12, 2020
Jason B. Luoma, Christina Chwyl, Geoff J. Bathje et al.
206 citations
Placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have resumed after a two-decade pause. Nine randomized, placebo-controlled trials published since 1994 examined psilocybin, LSD, ayahuasca, and MDMA. A significant mean between-groups effect size of 1.21 (Hedges g) was found, larger than typical effects for psychopharmacological or psychotherapy interventions. Effects were generally maintained at follow-up in the three studies that maintained a placebo control. Analyses support efficacy across post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. Larger trials with more diverse samples are needed to examine moderators and mediators and long-term effects.
The American journal of drug and alcohol abuse
January 1, 2019
Alan K Davis, Sara So, Rafael Lancelotta et al.
141 citations
Among people who used 5-MeO-DMT in a structured group setting with guided dosing and support, 80% of those previously diagnosed with depression and 79% of those previously diagnosed with anxiety reported their condition improved after use. Only 3% with depression and 2% with anxiety said their condition worsened. Greater improvement was linked to more intense mystical experiences and higher ratings of the experience's spiritual significance and personal meaning, but not to the intensity of challenging physical or psychological effects. The findings suggest potential therapeutic benefits, warranting controlled clinical trials.
Journal of psychopharmacology (Oxford, England)
July 1, 2018
Alan K Davis, Joseph P Barsuglia, Rafael Lancelotta et al.
137 citations
A survey of 515 adults who use 5-MeO-DMT found that consumption is infrequent and associated with profound positive subjective effects, including perceived spiritual and personal growth. Motivations for use were primarily spiritual and recreational, and many respondents reported perceived benefits consistent with potential psychotherapeutic effects. The study provides initial epidemiological data on usage patterns and subjective experiences with this psychoactive tryptamine.
ACS pharmacology & translational science
April 9, 2021
Gabrielle Agin-Liebes, Trevor F Haas, Rafael Lancelotta et al.
121 citations
Most people who used mescaline in natural settings reported lasting improvements in depression, anxiety, PTSD, and substance use disorders, with 68–86% of those with a history of these conditions noting subjective improvement after their most memorable experience. Those who improved reported stronger acute mystical-type, psychological insight, and ego dissolution effects (Cohen's d 0.7–1.5). For 35–50% of respondents, the mescaline experience ranked among the top five most spiritually significant or meaningful events of their lives. Psychological insight during the experience was linked to higher odds of improvement in depression, anxiety, and alcohol and drug use disorders. The authors call for controlled clinical trials to confirm these preliminary findings.
Psychopharmacology
December 10, 2019
Malin V. Uthaug, Rafael Lancelotta, Attila Szabó et al.
116 citations
Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately after the session. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience. Ratings of non-judgment increased and depression decreased from baseline to immediately post-session and at 7-day follow-up. Anxiety and stress ratings decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with affect ratings and positively with non-judgment ratings. The findings suggest that 5-methoxy-N,N-dimethyltryptamine produces changes in inflammatory markers and improves affect and non-judgment.
Journal of Neurochemistry
February 12, 2022
Johannes T. Reckweg, Malin V. Uthaug, Attila Szabó et al.
108 citations
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that acts primarily as an agonist at 5-HT1A and 5-HT2A receptors, with highest affinity for the 5-HT1A subtype. Its subjective effects include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that are usually short-lasting depending on route of administration. Individual dose escalation reliably induces a peak experience thought to be a core predictor of therapeutic efficacy. Observational studies and surveys suggest single exposure can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress.
Frontiers in Psychology
December 6, 2018
Rafael Lancelotta, Austin-Marley Windham-Herman, Kristel Peterson et al.
80 citations
Vaporized 5-MeO-DMT, a psychoactive substance from the Colorado River Toad, reliably produced strong mystical experiences in 20 individuals at a psychospiritual retreat. Participants received 50 mg of inhaled bufotoxin and completed the Mystical Experience Questionnaire. The average intensity was 4.17 out of 5, and 75% had a complete mystical experience. Compared to a prior psilocybin study, 5-MeO-DMT matched the intensity of a high dose (30 mg/70 kg) of psilocybin and significantly exceeded a moderate/high dose (20 mg/70 kg). The short duration may benefit clinical interventions and research on mystical-type experiences.
Journal of psychopharmacology (Oxford, England)
March 1, 2022
Malin Vedøy Uthaug, Alan K Davis, Trevor Forrest Haas et al.
64 citations
Mescaline, a naturally occurring psychoactive compound found in cacti such as Peyote and San Pedro, is used infrequently (once a year or less) by most English-speaking adults, primarily for spiritual exploration or connection with nature (74%). In a web-based survey of 452 respondents, very few reported drug craving (9%), legal problems (1%), or psychological problems (1%), and none sought medical attention. Acute mystical-type effects were rated as moderate, ego-dissolution and insight as slight, and challenging effects as very slight. About half of the sample had a psychiatric condition, and most (over 67%) reported improvements in these conditions after their most memorable mescaline experience. The findings suggest that mescaline may produce a psychedelic experience with spiritual significance and mental health benefits and has low abuse potential.
ACS Omega
December 2, 2020
Alexander M. Sherwood, Romain Claveau, Rafael Lancelotta et al.
38 citations
A multigram-scale process was developed to produce 5-MeO-DMT, a psychedelic natural product from the toad Incilius alvarius, for clinical use. An optimized Fischer indole reaction yielded 5-MeO-DMT freebase, which was converted to the 1:1 succinate salt, producing 136 g of crystalline active pharmaceutical ingredient with 99.86% purity by HPLC and a net yield of 49%. The report details in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization essential for clinical development.
Journal of Psychoactive Drugs
March 9, 2020
Rafael Lancelotta, Alan K. Davis
32 citations
A survey of 515 people who used the psychedelic 5-MeO-DMT found that most employed strategies to enhance benefits and reduce challenging effects. Among a subset of 116 one-time users, those who used such strategies reported more intense mystical-type experiences and greater lasting personal meaning and spiritual significance, while some strategies were linked to less challenging experiences. The findings suggest benefit-enhancement strategies are common and may boost positive acute and persisting effects, though causal relationships require further longitudinal study.
Frontiers in Psychiatry
November 29, 2022
Ana María Ortiz Bernal, Charles L. Raison, Rafael Lancelotta et al.
26 citations
Reactivations—similar to flashbacks—are common after using the psychedelic 5-MeO-DMT and are often neutral or positive rather than distressing. Analysis of survey data from 513 people who used 5-MeO-DMT outside clinical settings found that women, older age at first dose, higher education, and dosing in a structured group setting were linked to higher odds of reporting a reactivation. Higher mystical experience scores, greater personal wellbeing, and having had a non-substance-induced non-dual awareness experience were associated with neutral or positive emotional valence of the reactivation. The findings suggest reactivations are typically a benign byproduct of the experience, but more research is needed to identify those at risk for negative reactivations.
Journal of Psychedelic Studies
March 25, 2020
Malin V. Uthaug, Rafael Lancelotta, Ana María Ortiz Bernal et al.
25 citations
Among 27 respondents who used the psychedelic drug 5-MeO-DMT, those who received it by intramuscular injection (IM) reported a lower rate of reactivations (21%) compared to those who vaporized it (69%). The IM group also required fewer redoses, experienced release of physical tension more consistently, and had a slower onset of acute effects (1–6 minutes) versus the vaporization group (1–50 seconds). These findings suggest that the route of administration influences the frequency of reactivations, dosing patterns, physical sensations, and the timing of the drug's effects.
Journal of Psychedelic Studies
December 27, 2019
Nathan D. Sepeda, John M. Clifton, Laura Y. Doyle et al.
23 citations
People who used inhaled synthetic 5-MeO-DMT in a structured, supportive setting reported significantly more intense mystical experiences and enduring positive effects—such as greater meaningfulness, spirituality, and well-being—and fewer challenging experiences than those who used it in a non-structured context. In the structured context group, 83% had a complete mystical experience compared to 54% in the non-structured group. The findings suggest that a safe and supportive environment enhances the positive acute and lasting outcomes of 5-MeO-DMT.
International Journal of Transgender Health
March 19, 2025
Skylar J. Gaughan, Angie R. Wootton, Daphne Krantz et al.
6 citations
Transgender and gender-expansive (TGE) people use psychedelics in naturalistic, non-clinical settings to explore and affirm their gender identity. Interviews with 20 TGE individuals revealed three main themes: the mindset and physical setting of a psychedelic experience shape its quality; such experiences often increase self-acceptance of gender identity through greater self-compassion and a broader concept of gender; and participants reported both challenging effects like gender dysphoria and benefits like gender euphoria. The findings suggest clinicians should help TGE clients prepare a gender-affirming setting before psychedelic use and support shifts in gender understanding afterward.
Journal of Psychoactive Drugs
July 14, 2023
Christopher Timmermann, Aki Nikolaidis, Alan K. Davis et al.
4 citations
Spanish translations of three questionnaires measuring acute psychedelic effects—the Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ)—showed good psychometric properties in a sample of 442 native Spanish speakers. Confirmatory factor analysis confirmed that the factor structures matched the original English versions, and this consistency held across subgroups who had used LSD or psilocybin. Construct validity was supported by positive associations between the PIQ and MEQ and between these measures and changes in cognitive fusion, alongside negative associations with changes in prosocial behaviors. Predictive validity was indicated by strong relationships between persisting effects and scores on the MEQ and PIQ. The Spanish versions can be reliably used in research with Spanish-speaking populations.
Human Psychopharmacology Clinical and Experimental
March 17, 2022
Rafael Lancelotta
2 citations
The author confirms that the data supporting the findings of this study are available within the article and/or its supplementary materials.
January 8, 2026
Michael Esposito, Ana M Ortiz Bernal, Alan K. Davis et al.
preprint
A scoping review of 33 peer-reviewed studies on 5-MeO-DMT use in humans found that most interventional studies (13 of 15) used inhalation administration, though dosages and dosing regimens varied widely. Common outcomes measured include cognition, depression, post-traumatic stress disorder, and anxiety. The review highlights large heterogeneity in study design, dosing, and support, and suggests future research should explore different routes of administration and include more neuroimaging, qualitative, and longitudinal data.
Psychedelics
November 15, 2025
Meghan DellaCrosse, Shoval Gilead, Rafael Lancelotta et al.
Spanish-speaking individuals who had a memorable psilocybin or LSD experience reported two main themes: deep connection (to nature, others, the present moment, and the substance) and emotion-related experiences (from joy and peace to emotional processing, catharsis, and challenging experiences). The findings are based on a secondary qualitative analysis of open-ended survey responses from 379 Spanish-speaking participants. Similarities appeared across both substances, with some unique nuances. The work underscores the need for diverse populations in psychedelic research to improve generalizability and cultural relevance, and highlights the therapeutic potential of psychedelics while calling for culturally sensitive tools.
Drug and Alcohol Dependence
July 1, 2024
Alan K. Davis, Adam W. Levin, Rafael Lancelotta et al.
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