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.
Curr Top Behav Neurosci
January 1, 2018
Frederick S. Barrett, Roland R. Griffiths
268 citations
Mystical-type experiences, historically linked to classic hallucinogens, can be reliably measured with a validated questionnaire. Under double-blind conditions controlling for expectancy, psilocybin produces complete mystical experiences in most people, with effects that are dose-dependent and specific compared to placebo or an active control. These experiences have lasting positive impacts on mood, attitudes, and behavior, as reported by participants and community observers. In healthy volunteers, they generate enduring personal meaning; in patients, they are associated with reduced substance abuse and decreased anxiety and depression, including in those with life-threatening cancer. Parallels in brain activity between hallucinogens and meditative practices suggest a neural model based on changes in the default mode network.
Eur Neuropsychopharmacol
April 12, 2016
Mendel Kaelen, Leor Roseman, Joshua Kahan et al.
143 citations
Psychedelic drugs like LSD are being re-examined for therapeutic use, often combined with music during psychotherapy. In a placebo-controlled fMRI study with 12 healthy volunteers, researchers investigated how LSD and music together affect mental imagery. They found that the combination of LSD and music increased functional connectivity and information flow from the parahippocampal cortex to the visual cortex. This enhanced connectivity correlated with stronger eyes-closed visual imagery, including autobiographical imagery. The findings suggest a neural mechanism by which music and LSD synergistically enhance subjective experiences that may be valuable in therapeutic settings.
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.
Current topics in behavioral neurosciences
January 1, 2022
Tasha L. Golden, Susan Magsamen, Clara C. Sandu et al.
89 citations
A rapid scoping review of 43 studies on the role of setting and aesthetics in psychedelic experiences and therapies found broad consensus that setting matters, but rigorous, prospective tests of specific setting elements are lacking. The field agrees on the importance of setting yet remains without clear understanding of which elements affect outcomes, how they work, for whom, or under what conditions. Further research could improve psychedelic therapies and also inform non-psychedelic interventions.
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.
International Review of Psychiatry
July 4, 2018
Frederick S. Barrett, Katrin H. Preller, Mendel Kaelen
85 citations
Music listening has been used consistently from the beginning of therapeutic psychedelic research to guide experiences during the acute effects of psychedelic drugs. Recent findings indicate that music can support meaning-making, emotionality, and mental imagery after psychedelic administration, and suggest it plays an important role in facilitating positive clinical outcomes. This review examines the history, current research, and future directions of music in psychedelic therapy, arguing for more detailed and rigorous investigation into music's contribution to treating psychiatric disorders within this novel framework.
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
Psychedelic substances may acutely enhance creative task performance according to anecdotal reports, but empirical support is mixed. Clinical research suggests psychedelics can have lasting effects on mood and well-being, yet no neurocognitive framework connects acute cognitive changes to long-term mood improvements. This review operationalizes creativity within a cognitive control framework, evaluates existing evidence on psychedelics and creativity, and draws insights from how other psychoactive drugs acting on catecholamines enhance or impair cognition. The same framework links suggested psychedelic-induced improvements in creativity with enduring improvements in mood.
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.
Am J Psychiatry
January 1, 2024
Kelley C. O’donnell, Brian T. Anderson, Frederick S. Barrett et al.
31 citations
This critical response addresses misinterpretations and omissions in a commentary by Goodwin and colleagues on psilocybin-assisted therapy, arguing that the commentary misrepresents existing evidence and overlooks key methodological issues. The authors contend that the commentary fails to adequately discuss safety concerns, including adverse events and the potential for psychological distress, and omits important data on long-term outcomes. They emphasize the need for rigorous, balanced evaluation of psilocybin-assisted therapy's risks and benefits, cautioning against overstating positive outcomes while underreporting negative findings. The response calls for more transparent reporting and careful interpretation of clinical trial results.
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.
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.
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.