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
August 31, 2016
Theresa M. Carbonaro, Matthew P. Bradstreet, Frederick S. Barrett et al.
541 citations
In a survey of 1,993 people who recalled their worst 'bad trip' after taking psilocybin mushrooms, 39% ranked it among the top five most challenging experiences of their lives. Eleven percent put themselves or others at risk of physical harm, with factors such as higher dose, longer duration, and lack of physical comfort or social support increasing that risk. About 2.6% acted aggressively and 2.7% needed medical help. Among those whose experience was more than a year prior, 7.6% sought treatment for lasting psychological symptoms, with three cases linked to enduring psychotic symptoms and three to attempted suicide. Despite difficulties, 84% reported benefiting from the experience. The incidence of risky behavior or lasting distress is very low when psilocybin is given in controlled laboratory settings.
Journal of Psychopharmacology
October 11, 2017
Roland R. Griffiths, Matthew W. Johnson, William A. Richards et al.
528 citations
A double-blind trial compared a high dose of psilocybin (20 and 30 mg/70 kg) with a very low dose (1 mg/70 kg) in healthy adults who also undertook a program of meditation and spiritual practices. At six months, the high-dose groups, compared with the low-dose group, showed large, significant positive changes in interpersonal closeness, gratitude, life meaning, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. The enduring trait-level increases in prosocial attitudes and healthy psychological functioning were linked to the mystical-type experience occasioned by psilocybin and the rate of meditation or spiritual practices.
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.
Journal of Psychopharmacology
November 18, 2016
Frederick S. Barrett, Matthew P. Bradstreet, Jeannie‐marie Leoutsakos et al.
364 citations
A questionnaire was developed and validated to measure challenging psychological reactions to the hallucinogen psilocybin, often called 'bad trips.' Seven factors emerged: grief, fear, death, insanity, isolation, physical distress, and paranoia. These factors were linked to how difficult, meaningful, spiritually significant, and impactful on well-being participants rated their experiences. The factor structure was consistent regardless of gender or prior struggles with anxiety or depression. The questionnaire offers a tool for studying predictors and outcomes of such challenging experiences.
Journal of Psychopharmacology
February 20, 2021
Albert Garcia‐romeu, Frederick S. Barrett, Theresa M. Carbonaro et al.
101 citations
Psilocybin, a naturally occurring psychedelic, shows promise for treating mood and substance use disorders when given in structured settings. Most trials have adjusted the dose by body weight, but fixed dosing is simpler and cheaper. Analyzing data from ten previous studies (total 288 participants) that used weight-adjusted doses of 20 or 30 mg per 70 kg, or a fixed dose approximating 25 mg, no significant associations emerged between body weight or sex and the subjective effects (mystical, challenging, or intensity). Across body weights from 49 to 113 kg, body weight did not affect psilocybin's subjective effects, suggesting fixed dosing is as effective and more practical than weight-adjusted dosing.
Frontiers in Psychiatry
September 19, 2023
Hillary Jackson, Sara So, Abigail Yaffe et al.
87 citations
A large prospective survey of adults planning to take psilocybin outside clinical settings found that, on average, participants reported lasting reductions in anxiety, depression, and alcohol misuse, along with improvements in cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and decreases in neuroticism and burnout after use. However, a minority reported persisting negative effects: 11% at 2–4 weeks and 7% at 2–3 months after use, including mood fluctuations and depressive symptoms. The study included 2,833 respondents at baseline, 1,182 at 2–4 weeks, and 657 at 2–3 months post-use. Participants were primarily college-educated White men in the United States, mean age 40, who used dried psilocybin mushrooms (mean dose 3.1 grams) for self-exploration.
Frontiers in Psychology
July 25, 2017
Hollis Robbins, David Smooke, Frederick S. Barrett et al.
62 citations
Music chosen to support psilocybin sessions tends to be regular, predictable, and slowly building, with lower perceptual brightness during peak mystical experiences compared to the pre-peak period. An expert survey of therapists and researchers yielded 24 musical recommendations for peak effects and 24 for the pre-peak period. Qualitative and quantitative analyses of 22 stimuli revealed that peak-period music features formulaic phrase structure, continuous forward motion, and less brightness. These findings provide a basis for standardizing music selection in psychedelic research and therapy.
The International Journal of Neuropsychopharmacology
May 10, 2021
Natalie Gukasyan, David B. Yaden, Matthew W. Johnson et al.
56 citations
Psychedelic substances produce unusual changes in conscious experience, leading some to propose they offer unique insights into consciousness. However, psychedelics are unlikely to provide information relevant to the "hard problem of consciousness," which involves explaining how first-person experience emerges. Instead, they bear on multiple "easy problems of consciousness," involving relations between subjectivity, brain function, and behavior. This review discusses common meanings of "consciousness" regarding psychedelics and considers models of their effects on the brain linked to explanatory claims about consciousness. It calls for epistemic humility about psychedelic research's potential to explain the hard problem while noting ways psychedelics may advance study of specific aspects of consciousness.
Scientific Reports
October 2, 2020
Manoj K. Doss, Darrick G. May, Matthew W. Johnson et al.
52 citations
Salvinorin A, a κ-opioid receptor agonist and dissociative hallucinogen found in Salvia divinorum, alters human brain functional connectivity in ways similar to other hallucinogens. In a placebo-controlled, within-subject fMRI study, inhaled Salvinorin A tended to decrease functional connectivity within brain networks while increasing connectivity between networks, most notably attenuating the default mode network during peak effects. It reduced brainwide dynamic functional connectivity but increased brainwide entropic functional connectivity, though only the reduction survived statistical correction. Connectome-based classification models trained on dynamic connectivity accurately identified Salvinorin A scans, especially when using default mode network interactions. These findings suggest shared neural mechanisms across hallucinogen types.
Cerebral Cortex
September 12, 2017
Frederick S. Barrett, Katrin H. Preller, Marcus Herdener et al.
52 citations
Classic psychedelic drugs that activate serotonin 2A receptors alter how the brain responds to the changing tonal structure of music. In 25 healthy adults, brain imaging after placebo, LSD, and LSD combined with a serotonin 2A blocker showed that serotonin 2A signaling changes neural activity in regions for basic and higher-level music processing, memory, emotion, and self-referential thought. This signaling appears critical for tracking musical tonality and for the heightened emotionality, connectedness, and meaningfulness people often report after taking psychedelics. The findings clarify the neuropsychopharmacology of music perception and why music can feel profoundly altered during psychedelic experiences.
Neuron
January 20, 2023
Ceyda Sayalı, Frederick S. Barrett
40 citations
No Summary
Cannabis and Cannabinoid Research
April 2, 2018
Muhammad Waqas, Frederick S. Barrett, Nicolas J. Schlienz et al.
37 citations
A healthy 30-year-old man experienced auditory and visual hallucinations after inhaling vaporized cannabis containing 25 mg of THC in a controlled laboratory study. His scores on the Hallucinogen Rating Scale (HRS) were higher on the Volition, Intensity, Perception, and Somaesthesia subscales compared to maximum doses of cannabis, psilocybin, dextromethorphan, or salvinorin A from other studies. However, his Affect and Cognition subscale scores were lower than those for psilocybin and dextromethorphan, indicating the hallucinatory experience was qualitatively different from classic hallucinogens. The authors suggest cannabis-induced hallucinations may involve a unique pharmacological mechanism and should be considered as a potential adverse event in clinical cannabis use.
ACS Chemical Neuroscience
August 24, 2022
Manoj K. Doss, Frederick S. Barrett, Philip R. Corlett
21 citations
A critique of a Nature Medicine paper claiming psilocybin therapy reduces brain network modularity in depressed patients, an effect not seen with the SSRI S-citalopram. The authors identify multiple problems: inconsistent reporting of the primary clinical outcome, statistical flaws including a one-tailed test and a nonsignificant interaction, regression to the mean, ambiguous interpretation of resting-state fMRI data, and a missing reference to a similar study that undermines the justification for a one-tailed test. These issues cast doubt on the uniqueness and impact of the original findings and the media hype they generated.
bioRxiv (Cold Spring Harbor Laboratory)
June 25, 2017
Mendel Kaelen, Romy Lorenz, Frederick S. Barrett et al.
20 citations
preprint
Lysergic acid diethylamide (LSD) alters how the brain processes music, particularly by enhancing activity and connectivity in networks linked to music perception and emotion. Sixteen healthy volunteers listened to a 7-minute music piece during fMRI after taking either 75 mcg of LSD or a placebo. The acoustic feature of timbral complexity—the richness of the music's spectral distribution—drove the most pronounced changes in brain activity and connectivity under LSD. These changes correlated with increased feelings of wonder evoked by the music. The results suggest a neurobiological basis for why music is useful in psychedelic therapy.
Frontiers in Neuroergonomics
January 20, 2022
Yun Zhou, Frederick S. Barrett, Theresa M. Carbonaro et al.
17 citations
A psychoactive dose of psilocybin (10 mg/70 kg) occupied an average of 39.5% of serotonin 2A receptors in the brains of four healthy volunteers, as measured by PET imaging. The highest occupancy occurred in regions of the default mode network, including the subgenual anterior cingulate and bilateral angular gyri, with values between 63.12% and 74.72%. Individual variability in regional occupancy was marked. These findings support further research into how differences in receptor occupancy relate to psilocybin's acute and lasting effects.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
February 24, 2021
Sandeep M. Nayak, Natalie Gukasyan, Frederick S. Barrett et al.
10 citations
preprint
Classic psychedelics such as LSD or psilocybin may pose a significant seizure risk for people taking the mood stabilizer lithium. Analysis of online reports found that 47% of 62 accounts of combining lithium with a psychedelic involved seizures, and an additional 18% resulted in bad trips; 39% required medical attention. In contrast, none of 34 reports of the mood stabilizer lamotrigine combined with a psychedelic involved seizures, and most lamotrigine reports (65%) indicated no effect on the psychedelic experience. The authors provisionally conclude that psychedelic use with lithium carries a seizure risk, warranting further research.
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.
Psychedelic Medicine
June 1, 2023
Praachi Tiwari, Andrea Berghella, Ceyda Sayalı et al.
9 citations
Classic psychedelics may treat mood and substance use disorders by reversing learned helplessness, a well-studied phenomenon across mammals. The neural circuits underlying resilience to learned helplessness, including the dorsal raphe nucleus, overlap with those activated by psychedelics. Preclinical data show psychedelics improve performance in rodent behavioral despair tasks, supporting this hypothesis. The learned helplessness paradigm offers a robust model for investigating psychedelic mechanisms across behavioral, neurobiological, and clinical levels, potentially explaining transdiagnostic therapeutic effects.
bioRxiv (Cold Spring Harbor Laboratory)
March 11, 2025
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad et al.
8 citations
preprint
Psychedelics like psilocybin alter consciousness by reorganizing brain connectivity in a context-sensitive way. In the largest psychedelic neuroimaging dataset to date, 62 adults underwent functional MRI and EEG before and after ingesting 19 mg of psilocybin, during rest and naturalistic stimuli. Under psilocybin, brain signals during eyes-closed conditions became similar to those during eyes-open conditions, with increased global functional connectivity in associative regions and decreased connectivity in sensory areas. Machine learning linked subjective effects to structured neural activity patterns. Stronger self-dissolving effects were associated with more distinct neural representations and next-day mindset changes, revealing a state of 'embeddedness' where networks that usually segregate internal and external processing integrate coherently, aligning neural dynamics with context.
Drug and Alcohol Dependence
November 1, 2015
Frederick S. Barrett, Matthew W. Johnson, Roland R. Griffiths
7 citations
No Summary
bioRxiv (Cold Spring Harbor Laboratory)
May 24, 2022
Manoj K. Doss, Jason Samaha, Frederick S. Barrett et al.
6 citations
preprint
Different classes of psychoactive drugs—sedatives, dissociatives, psychedelics, stimulants, and cannabinoids—each produce unique patterns of effects on the conscious processes underlying episodic memory, depending on whether they act during encoding, consolidation, or retrieval. Reanalyzing confidence data from 10 published datasets (28 drug conditions) with signal detection models, the authors found that all drugs except stimulants impaired recollection when given at encoding; sedatives, dissociatives, and cannabinoids also impaired familiarity at encoding. Psychedelics at encoding enhanced familiarity and did not affect metamemory, while dissociatives and cannabinoids tended to enhance metamemory. Stimulants enhanced metamemory at encoding and retrieval but impaired it at consolidation. These distinct profiles may help explain drug-specific subjective phenomena such as sedative-induced blackouts or psychedelic déjà vu.
EClinicalMedicine
September 24, 2025
Megan Hosein, Matthew J. Reid, Sarah A. Walser et al.
5 citations
Psilocybin and other psychedelics show promise as a new class of psychiatric treatments, but their rapid development risks outpacing the guidelines and infrastructure needed for safe clinical integration. A consensus statement from the US National Network of Depression Centers (NNDC) Task Group on Psychedelics and Related Compounds, comprising psychiatrists, psychologists, neuroscientists, psychedelic researchers, and healthcare consultants, recognizes psilocybin's therapeutic potential while emphasizing the need for further research. Key gaps include understanding therapeutic dosage, efficacy across diverse populations, and long-term safety. The authors call for diversified funding, collaborative research, standardized provider training, and careful ethical consideration. They advocate for a balanced approach prioritizing rigorous science and equitable access, noting the single-country focus limits international generalizability.