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.
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.
Journal of psychopharmacology (Oxford, England)
September 1, 2020
Alan K Davis, John M 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.
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.
Journal of psychoactive drugs
January 1, 2018
Alan K Davis, Elise Renn, Austin-Marley Windham-Herman et al.
34 citations
Most people who underwent ibogaine detoxification for chronic opioid use reported lasting positive changes, including enhanced gratitude, authenticity, and appreciation for life. Those who responded well to treatment showed greater improvements in tolerating difficult feelings, coping with stress, reduced unhealthy anger, and increased inner peace, joy, love, and a sense of sacredness in life. They also reported heightened spiritual awareness and stronger connections in relationships. Challenges included psychological and health difficulties during treatment and problems with post-treatment integration. The findings point to the need for more integration and aftercare resources. Further rigorous experimental research is needed.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
Military psychology : the official journal of the Division of Military Psychology, American Psychological Association
January 1, 2024
Stacey B Armstrong, Yitong Xin, Nathan D Sepeda et al.
19 citations
Among 45 U.S. Special Operations Forces Veterans with risky alcohol use who completed ibogaine and 5-MeO-DMT treatment in Mexico, alcohol use dropped substantially from an average of 7.2 drinks per drinking day before treatment to 3.6 at one month and 4.0 at six months post-treatment. At one month, 24% were abstinent, 33% were non-risky drinkers, and 42% still risky drinkers; by six months, 16% were abstinent, 31% non-risky, and 53% risky. Responders (abstinent or non-risky) showed very large improvements in PTSD symptoms and cognitive functioning compared to non-responders, while demographics did not differ. The findings suggest psychedelic-assisted therapy may help those with complex trauma and alcohol misuse who have not responded to traditional treatments.
BMJ Open
May 1, 2023
Alan K Davis, Adam W Levin, Paul B Nagib et al.
19 citations
Psilocybin-assisted therapy may help treat post-traumatic stress disorder (PTSD), which current treatments often fail to relieve, especially in U.S. military veterans. This open-label pilot study will test two psilocybin doses (15 mg and 25 mg) combined with psychotherapy in 15 veterans with severe, treatment-resistant PTSD. The primary safety outcome tracks adverse events and suicidal ideation; the primary PTSD outcome uses the Clinician Administered PTSD Scale-5. Follow-up continues for 6 months after the second session. Results will be published in a peer-reviewed journal.
Journal of psychoactive drugs
January 1, 2025
Jacob S Aday, Emily K Bloesch, Alan K Davis et al.
16 citations
People who attended an ayahuasca retreat reported lasting increases in gratitude, feeling connected to nature, and appreciating nature. Surveys of 54 participants taken one week before, one week after, and one month after the retreat showed significant improvements at both follow-ups compared to baseline. The intensity of mystical-type experiences and awe during ayahuasca sessions weakly to moderately correlated with these increases, while the number of ceremonies attended did not. Older participants reported less intense mystical and awe experiences. The findings suggest that the quality of psychedelic experiences, particularly mystical and awe states, may foster prosocial changes in gratitude and nature connection.
Journal of substance use and addiction treatment
June 1, 2023
Angela M Haeny, Joel A Lopez, Pamela A Colón Grigas et al.
10 citations
Among 211 racially and ethnically minoritized (REM) adults in the US and Canada, retrospective reports indicated that after their most memorable psychedelic experience, alcohol use and drug use were perceived to have decreased. The reduction in alcohol use was greater for Indigenous participants, those who took a high dose, those with a stronger ethnic identity, and those who reported fewer depressive symptoms. Perceived increases in psychological flexibility and reductions in racial trauma symptoms appeared to mediate the link between acute psychedelic effects and reduced substance use. The authors suggest psychedelic experiences may help REM people reduce alcohol and drug use by increasing psychological flexibility and easing racial trauma, but call for longitudinal replication.
Journal of psychoactive drugs
June 18, 2025
Rafaelle Lancelotta, Meghan DellaCrosse, Diana Quinn et al.
7 citations
Among 346 LGBTQIA+ individuals, mostly White and in their early 30s, those who used psychedelics reported improvements in mental health and shifts in gender and sexual identity. Retrospective reports showed large reductions in traumatic stress, depression, and anxiety, along with increased psychological flexibility. A significant link emerged between the intensity of the psychedelic experience and greater self-acceptance and sexual identity exploration. Most participants (77%) saw therapeutic potential in psychedelics for gender dysphoria, and 65% reported changes in gender identity attitudes after use. The findings suggest psychedelics may support identity exploration and mental health in this population, warranting further research.
Social work
April 1, 2025
Maha N Mian, Jordan Horan, Taweh Hunter et al.
1 citation
Social workers rated SSRI-assisted therapy as significantly more acceptable, appropriate, and feasible than MDMA-assisted therapy for treating adolescents with treatment-resistant PTSD, with medium-to-large effect sizes. Perceptions of MDMA risk were higher among those who read about MDMA-assisted therapy, and greater psychedelic stigma correlated with higher perceived risk of MDMA. However, more psychedelic knowledge was linked to less stigma and lower perceived risk. These findings suggest that social workers' concerns about MDMA-assisted therapy for adolescents may hinder clinical trial recruitment and future implementation.
Journal of psychoactive drugs
February 13, 2025
Yitong Xin, Roland R Griffiths, Alan K Davis
1 citation
Among ayahuasca users who report encountering an entity during their experience, males and females show different patterns of religious belief change. Before the encounter, males were more likely to identify as atheists and less likely to hold religious beliefs than females. After the encounter, both sexes became less atheist or agnostic and more religious, but the shift was larger for males: the proportion of religious males rose significantly, while the increase for females was not statistically significant. These results suggest that sex is linked to how religious beliefs shift after an entity encounter, pointing to the importance of considering sex in psychedelic research on spirituality.
Expert review of clinical pharmacology
June 11, 2025
Victor Pablo Acero, Taylor A Flatt, Peter M Gooch et al.
Psychedelic compounds can produce rapid and lasting depression symptom reduction after one or two administrations paired with psychotherapy, unlike traditional antidepressants. Current evidence on their antidepressant mechanisms is fragmented across biological, psychological, social, and spiritual domains. This review identifies key mechanisms in each domain, comparing them with those of conventional antidepressants to highlight overlaps and differences. The authors caution that focusing too narrowly on discrete pathways may limit progress, as psychedelics likely work through complex, interwoven processes. Future research should examine how suprapharmacological factors—set, setting, therapy modality, and integration—shape outcomes, moving beyond frameworks used for standard antidepressants.