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.
Translational Psychiatry
November 8, 2021
Manoj K. Doss, Michal Považan, Monica D Rosenberg et al.
343 citations
Psilocybin therapy increased cognitive flexibility for at least four weeks in 24 patients with major depressive disorder, though these improvements were not linked to antidepressant effects. One week after treatment, glutamate and N-acetylaspartate concentrations decreased in the anterior cingulate cortex (ACC), and functional connectivity dynamics increased between the ACC and posterior cingulate cortex. Surprisingly, larger increases in this neural flexibility were associated with smaller gains in cognitive flexibility. Baseline brain connectivity from the ACC predicted cognitive flexibility improvements, with greater baseline connectivity linked to better baseline flexibility but less improvement. The findings suggest that while some increase in neural dynamics may help shift from rigid states, larger persisting increases may be less beneficial.
Journal of Psychopharmacology
May 14, 2019
Albert Garcia‐romeu, Alan K. Davis, Fire Erowid et al.
286 citations
In a survey of 343 people who had problematic alcohol use for an average of seven years and then used psychedelics in non-clinical settings, 83% no longer met criteria for alcohol use disorder after the experience. Most respondents were White males in the USA who took moderate or high doses of LSD or psilocybin. They rated the experience as highly meaningful and insightful, and 28% said changes in life priorities or values helped reduce alcohol misuse. Greater dose, insight, mystical-type effects, and personal meaning were linked to larger reductions in drinking. The results suggest naturalistic psychedelic use may reduce problematic alcohol use, supporting further research into psychedelic-assisted treatment.
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.
Journal of Psychopharmacology
January 9, 2021
Alan K. Davis, Frederick S. Barrett, Sara So et al.
166 citations
A new questionnaire, the Psychological Insight Questionnaire, was developed to measure psychologically insightful experiences during psychedelic use. Among 1,661 psilocybin and LSD users, the 23-item measure showed two subscales: Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights. Scores correlated strongly with an existing insight measure and moderately with mystical and challenging experience questionnaires. They also correlated with retrospectively reported increases in psychological flexibility, well-being, and life satisfaction attributed to a memorable psychedelic experience. The questionnaire predicted unique variance in these outcomes beyond mystical and challenging effects, suggesting it may help understand how psychological insight contributes to psychedelics' enduring 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.
Journal of psychopharmacology (Oxford, England)
September 1, 2020
Alan K. Davis, John Clifton, Eric G Weaver et al.
144 citations
Inhaling N,N-dimethyltryptamine (DMT) can trigger encounters with seemingly autonomous entities. A survey of 2,561 people (average age 32, 77% male) found that these encounters primarily involve visual and extrasensory perception, such as telepathy. Entities are most often described as beings, guides, spirits, aliens, or helpers. Although 41% of respondents felt fear, the dominant emotions were love, kindness, and joy, both in the respondent and attributed to the entity. Most believed the entity was conscious, intelligent, and benevolent, existing in a real but different dimension. 69% received a message, and 19% a prediction. Over half of those who were atheist before no longer identified as atheist afterward.
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 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.
PLoS One
March 14, 2024
Adam W. Levin, Rafaelle Lancelotta, Nathan D. Sepeda et al.
65 citations
In a small randomized trial of psilocybin-assisted therapy for adults with major depressive disorder, the therapeutic alliance between participants and facilitators strengthened from the final preparation session to one week after the intervention. A stronger alliance before the psilocybin sessions predicted lower depression scores at 4 weeks, 6 months, and 12 months afterward. Stronger alliance also correlated with more intense mystical experiences and psychological insight during the drug sessions, which in turn predicted better depression outcomes. The findings suggest the therapeutic relationship is important for treatment success.
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.
Journal of Psychedelic Studies
November 1, 2017
Alan K. Davis, Joseph P Barsuglia, Austin-Marley Windham-Herman et al.
60 citations
A survey of 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 found that most (80%) reported the drug eliminated or drastically reduced withdrawal symptoms, and half said it reduced opioid craving, with some reporting that reduction lasting at least three months. Thirty percent never used opioids again after treatment, and over half of those abstainers had been abstinent for at least one year. Although 70% relapsed, 48% decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had lower rates of depressive and anxious symptoms and higher well-being. The results suggest ibogaine is associated with reductions in opioid use and improved psychological outcomes.