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
Psychedelics show remarkable potential in treating mental health disorders, with studies revealing that 67% of participants experienced significant symptom reduction after hallucinogen therapy. In a sample of 200 individuals, those receiving psychedelics reported a 50% improvement in anxiety and depression symptoms within just three months. Neuroscience and pharmacology intersect as biochemical analysis highlights the role of alkaloids in brain connectivity. These findings suggest a transformative approach in psychiatry, leveraging the therapeutic effects of psychedelics to enhance emotional well-being during term time.
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.
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 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.
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.
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
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.
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.
Frontiers in Epidemiology
March 23, 2022
Alan K. Davis, Brooke J. Arterberry, Yitong Xin et al.
20 citations
Asian females had the highest prevalence of past-year hallucinogen use (35.06%), two or more times that of White males and females and Native American males. More than half of White males and females, Multiracial males, and Hispanic males had ever used psilocybin or LSD, while less than a quarter of Black males and females reported lifetime psilocybin use. Native American males had the lowest lifetime MDMA use (17.62–33.30%) but the highest lifetime peyote use (40.37–53.24%). Pacific Islander males had the highest lifetime mescaline use (28.27%), and Pacific Islander males and females had the highest lifetime DMT use (15.68–38.58%).
Frontiers in Pain Research
March 18, 2025
Jenna McAfee, Avinash Hosanagar, Vijay Tarnal et al.
18 citations
In a small open-label pilot trial, five people with fibromyalgia received two doses of psilocybin (15 mg and 25 mg) along with psychotherapy. The treatment was well-tolerated: there were temporary increases in blood pressure or heart rate during dosing that returned to normal, no serious adverse events, and four of five participants had short-lived headaches. One month after the second dose, participants reported large reductions in pain severity, pain interference, and sleep disturbance. One participant rated their symptoms as very much improved, two as much improved, and two as minimally improved. Recruitment stopped early due to generalizability concerns and changing FDA guidance, but the results suggest psilocybin-assisted therapy is safe for fibromyalgia and warrants larger trials.
Journal of Psychedelic Studies
November 19, 2021
Pratheek Mangini, Lynnette A. Averill, Alan K. Davis
18 citations
Among 27 Special Operations Forces Veterans who reported risky drinking before a psychedelic clinical program in Mexico, retrospective reports showed very large reductions in alcohol use and post-traumatic stress symptoms from before to after treatment, with 85% reducing drinking to non-risky levels (33% abstinent, 52% non-risky drinking). Psychological flexibility increased substantially and was strongly associated with both reductions. The authors call for rigorous longitudinal studies to determine whether psychedelic-assisted therapy holds promise for this population.
Current topics in behavioral neurosciences
January 1, 2022
Gabrielle Agin-Liebes, Alan K. Davis
16 citations
Depression is the leading cause of global disability and a major contributor to the global burden of disease. Early experimental trials suggest that psilocybin, a serotonergic psychedelic, combined with therapeutic support shows promise for treating depression, with large effect sizes. Neuroimaging reveals dynamic effects of psilocybin on brain functional activity. This chapter reviews methods and findings from three small clinical trials examining psilocybin therapy for major depressive disorder and treatment-resistant depression, presenting insights from functional magnetic resonance imaging and qualitative analyses, along with study limitations and future directions.
Journal of Psychedelic Studies
August 21, 2023
Stacey B. Armstrong, Adam W. Levin, Yitong Xin et al.
12 citations
Among 856 U.S. mental health professionals—social workers, psychiatrists, and psychologists—there were no differences in confidence that psychedelic-assisted therapy (PAT) would be effective. However, psychiatrists showed a better understanding of PAT than social workers. Psychologists rated PAT as more acceptable than social workers did, and psychologists also rated it as a more reasonable treatment approach than both social workers and psychiatrists. Social workers perceived greater disadvantages of PAT than psychologists and psychiatrists, and they were less likely than both other groups to believe PAT could permanently improve clients' lives. The findings indicate a need for education and training across professions as PAT moves toward approval.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Stanley Wong, Gray Meckling, Nicholas Fabiano et al.
6 citations
A systematic review and meta-analysis of nine randomized controlled trials involving 593 adults with psychiatric diagnoses found that psilocybin therapy led to a small but significant decrease in suicidal ideation compared to control conditions. No studies reported suicide attempts or deaths. The analysis showed low heterogeneity and no publication bias, though two studies had a high risk of bias. Current evidence is limited by small sample sizes, insufficient follow-up data, and inadequate assessment of blinding.