JAMA Psychiatry
November 4, 2020
Mary P Cosimano, Alan K. Davis, Frederick S. Barrett et al.
1,269 citations
Two doses of psilocybin (20 and 30 mg per 70 kg) combined with supportive psychotherapy produced large, rapid antidepressant effects in adults with major depressive disorder who were not taking other antidepressants. In a randomized waiting list-controlled trial with 24 completers, depression scores on the GRID-Hamilton scale dropped from a mean of 22.8 at baseline to 8.0 one week after the second session, compared with 23.8 at the same time point in the delayed-treatment group. Seventy-one percent of participants showed a clinically significant response at week 1, and 58% met remission criteria. Effects persisted through the four-week follow-up.
Journal of Psychopharmacology
February 1, 2022
Natalie Gukasyan, Alan K. Davis, Frederick S. Barrett et al.
419 citations
In patients with moderate to severe major depressive disorder, psilocybin-assisted therapy produced large and sustained decreases in depression severity through 12 months. Scores on the GRID-Hamilton Depression Rating Scale dropped substantially from baseline at 1, 3, 6, and 12 months (effect sizes of 2.3, 2.0, 2.6, and 2.4, respectively). At 12 months, 75% of participants showed a 50% or greater reduction in symptoms and 58% achieved remission. No serious adverse events linked to psilocybin occurred during long-term follow-up, and no participants used psilocybin outside the study. Ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted greater well-being at 12 months but did not predict depression improvement.
Journal of contextual behavioral science
January 1, 2020
Alan K. Davis, Frederick S. Barrett, Roland R. Griffiths
369 citations
Acute subjective effects of psychedelics, particularly mystical and insightful experiences, are linked to reductions in depression and anxiety. In a cross-sectional survey of 985 people who had used a psychedelic, increases in psychological flexibility fully mediated the relationship between these acute effects and decreases in depression and anxiety. This suggests that psychological flexibility may be a key mechanism through which psychedelics produce therapeutic benefits. Future prospective studies are needed to test this directly.
Neuroscience & Biobehavioral Reviews
March 16, 2020
Jacob S. Aday, Cayla M. Mitzkovitz, Emily K. Bloesch et al.
260 citations
A systematic review of 34 experimental studies on classic psychedelics with follow-up periods of at least two weeks found lasting changes in personality, attitudes, depression, spirituality, anxiety, wellbeing, substance misuse, meditative practices, and mindfulness. Psilocybin was the most commonly administered drug. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were linked to these long-term psychological changes. With proper screening, preparation, supervision, and integration, participants reported few aversive side effects. The review calls for larger, more diverse samples, longer longitudinal designs, stronger control conditions, and standardized dosages in future research.
PLoS ONE
April 23, 2019
Roland R. Griffiths, Ethan Hurwitz, Alan K. Davis et al.
249 citations
Experiences interpreted as personal encounters with God, whether occurring naturally or after taking psychedelic drugs, share striking similarities. In an online survey of over 4,200 people, those who had a nondrug encounter most often called it God, whereas those who had a psychedelic encounter most often called it Ultimate Reality. Regardless of origin, most participants vividly remembered the encounter as involving a conscious, benevolent, intelligent, sacred, eternal, and all-knowing presence. About half of all encounters met criteria for a complete mystical experience. More than two-thirds of self-identified atheists no longer identified as atheist afterward.
ACS Pharmacol Transl Sci
March 5, 2021
Jacob S. Aday, Alan K. Davis, Cayla M. Mitzkovitz et al.
228 citations
People who are more open, accepting, and prone to absorption, as well as those who enter a psychedelic session with a mindset of surrender, are more likely to have positive, mystical-type experiences. Conversely, individuals who are low in openness or surrender, or who arrive in a preoccupied, apprehensive, or confused state, are more likely to experience adverse reactions. A systematic review of 14 studies found that sex is not a robust predictor of drug effects, but certain brain-based measures—such as 5-HT2AR binding potential, executive network node diversity, and rACC volume—may serve as biomarkers. Older age and prior experience with psychedelics are linked to less intense effects, suggesting users may become slightly less sensitive after repeated use.
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.
Frontiers in Psychiatry
January 22, 2020
Earth Erowid, Fire Erowid, Albert Garcia‐romeu et al.
155 citations
A cross-sectional, self-report survey found that people who use psychedelics reported reductions in problematic substance use, including alcohol, opioids, and stimulants. The authors note that because the study is cross-sectional and relies on self-reports, it cannot determine whether psychedelics caused these changes. However, the results suggest a potential for psychedelics to reduce problematic substance use and support further clinical research into psychedelic-assisted treatment for substance use disorders.
Psychopharmacology
December 10, 2019
Malin V. Uthaug, Rafael Lancelotta, Attila Szabo 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 Szabo 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.
Journal of Psychoactive Drugs
September 1, 2021
Alan K. Davis, Gabrielle Agin-Liebes, Megan España et al.
103 citations
Clinical psychologists in the United States hold cautiously favorable attitudes toward psychedelic-assisted therapy but express concerns about psychiatric and neurocognitive risks. Most surveyed psychologists report lacking a full understanding of psychedelics' effects and indicate a need for additional consultation. They endorse positive beliefs about the potential of psychedelic treatment and the need for further research. The findings highlight the need to increase education and training about psychedelics for psychologists to enhance knowledge and reduce stigma.
Drugs Education Prevention and Policy
December 10, 2020
Monnica T. Williams, Alan K. Davis, Yitong Xin et al.
100 citations
Psychedelics such as psilocybin, LSD, and MDMA may reduce symptoms of racial trauma among Black, Indigenous, and other people of color (BIPOC) after a racist experience. In a cross-sectional survey of 313 diverse BIPOC in the US and Canada, participants retrospectively reported mental health symptoms 30 days before and 30 days after using a psychedelic. Analysis showed significant decreases in traumatic stress, depression, anxiety, and stress following the experience. A strong positive relationship emerged between acute psychedelic effects (mystical-type, insight, and challenging experiences) and reductions in psychopathology, even after controlling for prior discrimination and time since the experience. The findings suggest psychedelics could lessen the negative impact of racial trauma, though further research on psychedelic-assisted therapy for race-based trauma is needed.
Chronic Stress
August 12, 2020
Alan K. Davis, Lynnette A. Averill, Nathan D. Sepeda et al.
83 citations
Among U.S. Special Operations Forces Veterans who completed a psychedelic treatment program with ibogaine and 5-methoxy-N,N-dimethyltryptamine in Mexico between 2017 and 2019, retrospective reports showed very large reductions in suicidal ideation, cognitive impairment, PTSD symptoms, depression, and anxiety from 30 days before to 30 days after treatment, along with a large increase in psychological flexibility. Increased psychological flexibility was strongly linked to reduced cognitive impairment and mental health symptoms. Most participants rated the experience among the top five most personally meaningful, spiritually significant, and psychologically insightful experiences of their lives. The findings are preliminary due to the retrospective, self-report, non-randomized design.
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.
Chronic Stress
January 1, 2021
Alan K. Davis, Yitong Xin, Nathan D. Sepeda et al.
66 citations
Among 313 Black, Indigenous, and people of color (BIPOC), acute psychedelic effects were associated with decreases in racial trauma symptoms. Greater psychological insight and less intense challenging experiences during the psychedelic session predicted larger symptom reductions. Increases in psychological flexibility partially mediated these improvements. The findings suggest psychedelics may help reduce racial trauma in BIPOC, with psychological flexibility playing a key mediating role.
Journal of Psychoactive Drugs
January 10, 2022
Nicolas G. Glynos, Jennifer Pierce, Alan K. Davis et al.
39 citations
In a survey of 354 North American adults with fibromyalgia, nearly 30% reported having used a psychedelic, most commonly LSD or psilocybin mushrooms. Most users rated their experience as neutral (59.4%) or positive (36.8%), and fewer than 3% reported negative effects on health or pain. Among the 12 participants who used a psychedelic specifically to treat chronic pain, 11 said their symptoms improved. Regardless of past use, most respondents believed psychedelics could help treat chronic pain and would join a clinical trial for such a treatment. The findings support further research into psychedelic-based therapies for fibromyalgia.
Journal of Psychoactive Drugs
January 11, 2022
Terence H. W. Ching, Alan K. Davis, Yitong Xin et al.
34 citations
Among 92 Asian adults in North America who used psychedelics in response to racial discrimination, racial trauma symptoms improved moderately (d = 0.52) from 30 days before to 30 days after their most meaningful psychedelic experience. Higher-intensity insightful experiences were linked to stronger ethnic identity through reductions in trauma symptoms, while lower-intensity challenging experiences also contributed to symptom improvement and identity strengthening. The findings suggest that both insightful and challenging psychedelic experiences may help alleviate racial trauma and support ethnic identity in this population.
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.
Nature medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
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.
J Affect Disord
December 27, 2022
Aki Nikolaidis, Rafaelle Lancelotta, Natalie Gukasyan et al.
24 citations
Three reproducible subtypes of psychedelic experience were identified in a large sample of 985 people using machine learning. Subtypes differed in baseline demographics, mental health measures, and drug type and dose. Experiences linked to enduring improvements in anxiety, depression, and psychological wellbeing were characterized by greater personal and mystical insight. The subtypes were consistent across multiple psychedelic substances. Findings suggest that fostering insight experiences may be key to maximizing clinical benefits.
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.
Drug Science Policy and Law
January 1, 2017
Alan K. Davis, Harold Rosenberg
22 citations
Both recreational and problematic MDMA/ecstasy users could benefit from harm reduction interventions. A web-based survey assessed how often 104 American and 80 British ecstasy users employed 19 self-initiated harm reduction strategies over two months. At least 75% of participants used 11 of the 19 strategies at least once, regardless of country or frequency of use. When differences occurred, larger proportions of Americans used the strategies. Many less-used strategies are not applicable every time. Testing ecstasy for MDMA, other stimulants, and adulterants is recommended for all users, as it is not a diverted pharmaceutical of known quality.
JAMA Health Forum
June 17, 2022
Kevin F. Boehnke, Alan K. Davis, Jenna McAfee
20 citations
Oregon's 2020 decriminalization of psilocybin and other illicit substances mirrors the trajectory of cannabis liberalization over the past 25 years, driven by arguments for compassionate use, personal freedom, and frustration with federal drug policy. The authors argue that psychedelics are poised to follow a similar pattern, reinforced by FDA breakthrough therapy designations for psilocybin and MDMA. They caution that medical cannabis policies expanded access and industry power but failed to integrate cannabis into medical practice, track health outcomes, or promote safe use, leading to increased emergency department visits and highly concentrated products. Extrapolating to psychedelics, they find this lack of integration troubling because oversight by trained monitors in clinical trials likely decreases adverse reactions and enhances treatment success.