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Frederick S. Barrett

Johns Hopkins University, Johns Hopkins Medicine

73 papers in the library · 7,719 citations · publishing 2014-2026

Papers

Considerations and cautions for the integration of psilocybin into routine clinical care: a consensus statement from the US National Network of Depression Centers' Task Group on Psychedelics and Related Compounds

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.

Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder

Journal of Psychedelic Studies September 4, 2025 Alan K. Davis, Meghan DellaCrosse, Nathan D. Sepeda et al. 4 citations

Over a five-year follow-up period, psilocybin-assisted therapy produced significant and sustained reductions in depression for people with major depressive disorder. Among the 18 participants who completed the study, 67% remained in remission for at least five years after treatment. Anxiety and functional impairment also improved. Qualitative interviews revealed lasting positive changes in mindset, emotional health, and relationships, including enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported. These findings support the long-term efficacy and safety of psilocybin-assisted therapy for reducing depressive symptoms and improving mental health.

Impact of Psilocybin on Peripheral Cytokine Production

Psychedelic Medicine February 28, 2024 Dana D. DiRenzo, Jamie Perin, Erika Darrah et al. 4 citations

A preliminary study suggests that psilocybin may cause a temporary increase in cytokine production within one week after administration, but this effect is not consistent across different patient populations. The findings indicate that peripheral cytokine production is possibly altered by psilocybin.

Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

Schizophrenia Bulletin April 17, 2025 Nathan H. Heller, Frederick S. Barrett, Tobias Buchborn et al. 3 citations

Visual hallucinations in Lewy body diseases (Parkinson's disease and dementia with Lewy bodies) and those induced by serotonergic psychedelics (psilocybin, mescaline) share overlapping phenomenology and neural mechanisms, despite different underlying causes. Both conditions produce visual aberrations from minor distortions to complex hallucinations, including illusory motion and entity encounters. Neuroimaging shows a common pattern of overactive associative cortex and underactive sensory cortex. Serotonin 2A receptor modulation is involved in both: psychedelics act through 5-HT2A and 5-HT1A receptors, while in Lewy body diseases, 5-HT2A receptor upregulation correlates with increased hallucinations, and blocking it with pimavanserin reduces them. Shared cortical signatures include reduced visual evoked responses and shifts toward visual excitation.

Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity

bioRxiv (Cold Spring Harbor Laboratory) March 2, 2022 Andrew Gaddis, Daniel E. Lidstone, Mary Beth Nebel et al. 2 citations preprint

Psilocybin, a classic psychedelic, alters perception and cognition by affecting connectivity between the thalamus and cortex. Using a novel analysis of resting-state fMRI data, this study found that psilocybin changes the functional organization within specific thalamic nuclei—primarily the mediodorsal and pulvinar nuclei—and alters their connections with visual and default mode networks. These changes correlated with subjective drug effects. When the thalamus was treated as a single unit, a numerical but not statistically significant increase in thalamocortical connectivity was observed, suggesting that psilocybin causes widespread modest increases offset by strong focal decreases in relevant nuclei.

Trip sitting or just sitting? Session facilitators substantially influence psychedelic experiences in clinical trials but not in healthy ones

Psychiatry Research February 13, 2026 Sean P. Goldy, Nathan D. Sepeda, Samantha Hilbert et al. 1 citation

The acute subjective effects of psychedelics are known to predict therapeutic benefits like reduced depression and anxiety. Session facilitators—who support participants before, during, and after dosing—are a key part of the setting, but their influence on subjective effects was unclear. Analyzing data from 9 psilocybin studies with 298 participants, 670 sessions, and 60 facilitators, multilevel models showed facilitators accounted for negligible variance (0.8%) in healthy volunteers but greater variance in clinical samples (13.6%), after controlling for study and participant differences. This suggests facilitators may play a clinically meaningful role in shaping outcomes for patient populations, comparable to or exceeding therapist effects in traditional psychotherapy (~8%).

Development of the Japanese version of the Challenging Experience Questionnaire

Neuropsychopharmacology Reports November 8, 2024 Hideaki Tani, Kengo Yonezawa, Keisuke Kusudo et al. 1 citation

A Japanese version of the Challenging Experience Questionnaire (CEQ) was developed to assess difficult aspects of psychedelic experiences in Japanese speakers. Following international guidelines for translation and cultural adaptation, two psychiatrists independently translated the original English CEQ into Japanese, reconciled the versions, and had them back-translated into English. The original authors reviewed the back-translation and approved the final version after revisions. The resulting questionnaire enables evaluation of challenging experiences during psychedelic-assisted therapy for Japanese-speaking populations, though further studies are needed to confirm its reliability and validity.

Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds

April 28, 2022 Manoj K. Doss, Frederick S. Barrett, Philip R. Corlett 1 citation preprint

A critical commentary identifies problems in a previously published study on psilocybin therapy. The authors argue that the original paper drew unsupported causal conclusions from correlational data, failed to account for placebo effects and participant expectations, and used statistical methods that inflated the apparent strength of the findings. The commentary suggests the original study's claims about psilocybin's therapeutic mechanisms are not justified by the evidence presented.

Integrating the Mystical Experience Questionnaire Into a Broader Psychometric Framework: English Validation of the Psychedelic Experience Scale and Comparison of Psilocybin and LSD Sessions Across Two Controlled Settings.

International Journal of Methods in Psychiatric Research June 1, 2026 Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.

The eight-factor structure of the Psychedelic Experience Scale (PES48), which includes the Mystical Experience Questionnaire (MEQ30) and additional factors for paradoxicality, connectedness, visual experience, and distressing experience, is valid for use in English. Analysis of 280 measurements from 145 healthy participants in four placebo-controlled psilocybin studies found that six subscales have high internal consistency, one good, and one acceptable. Both the MEQ30 and MEQ40 models show acceptable to good model fits, with better fits in English than in German. All six MEQ40 scale means were higher in English data, suggesting that the PES48 provides a broader conceptualization of mystical and non-mystical psychedelic experiences, and that setting may influence mystical experience.

Psilocybin-induced neurocardiogenic syncope: a case report.

Psychopharmacology May 28, 2026 Mazen A Atiq, Eli Weisman, Rodrigo B Guerra et al.

A healthy 35-year-old man experienced a rare hypotensive adverse event—neurocardiogenic syncope (fainting)—about 60 minutes after taking 25 mg of oral psilocybin in a clinical trial. His blood pressure dropped to 93/51 mmHg, with rapid heart rate and sweating, but he stabilized quickly with leg elevation and oral hydration. The episode may have been triggered by upright seated posture, restrictive EEG equipment, and anxiety about upcoming transcranial magnetic stimulation. Fewer than one-quarter of contemporary psychedelic trials report systematic adverse event assessment, highlighting the need for transparent documentation of both hypertensive and hypotensive events as psilocybin moves toward potential FDA approval.

Integrating the Mystical Experience Questionnaire Into a Broader Psychometric Framework: English Validation of the Psychedelic Experience Scale and Comparison of Psilocybin and LSD Sessions Across Two Controlled Settings

Repository for Publications and Research Data (ETH Zurich) April 30, 2026 Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.

The Psychedelic Experience Scale (PES48) has an eight-factor structure that includes the well-validated Mystical Experience Questionnaire (MEQ30) plus four additional factors: paradoxicality, connectedness, visual experience, and distressing experience. This study tested whether the full eight-factor structure is valid in English, using data from 280 PES measurements from 145 healthy participants in four placebo-controlled psilocybin studies. Six of the eight subscales showed high internal consistency, one good, and one acceptable. Confirmatory factor analysis indicated acceptable to good model fits for the MEQ30 and MEQ40, with English data showing better fits than the German validation sample. The findings suggest the PES48 is a valid psychometric tool in English, enabling broader measurement of mystical and non-mystical aspects of psychedelic experience.

Acute Cardiovascular Effects of Psilocybin: A Pooled Analysis of 14 Studies with Safety Recommendations

medRxiv Preprint Server April 28, 2026 Sandeep M. Nayak, Nathan D. Sepeda, Matthew Nielsen Dick et al. preprint

Psilocybin is being studied as a treatment for psychiatric and neurologic conditions, but there is limited comprehensive data on its cardiovascular safety. Current clinical trials typically exclude people with blood pressure of 140/90 mmHg or higher, a cutoff set conservatively without strong empirical evidence.

Mystical dynamics: renewal, luminous light, and ego disintegration as key features associated with mystical oneness—a psychometric analysis using the PES100 in controlled psychedelic studies

Religion Brain & Behavior March 31, 2026 Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.

After administration of LSD, psilocybin, mescaline, or DMT, mystical oneness—the core of mystical experience—showed dose-sensitive strong correlations with luminous light and renewal, and a moderate-to-strong correlation with ego disintegration. These findings from 386 healthy participants across 15 studies support a broader, dynamic model of mystical experience, where mystical oneness unfolds with ego disintegration, renewal, and luminous light. The results offer insights for psychedelic-assisted therapy.

Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.

Journal of psychopharmacology (Oxford, England) February 5, 2026 Benjamin R. Lewis, Matthew J Reid, Andrew M Novick et al.

Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.

Roland R. Griffiths, psychopharmacology pioneer: Abuse liability, alcohol, nicotine, caffeine, benzodiazepines, and psychedelics.

Journal of psychopharmacology (Oxford, England) January 1, 2026 Jack E Henningfield, Frederick S. Barrett, Suzette M Evans et al.

Roland R. Griffiths was a highly influential scientist in behavioral and neuropsychopharmacology, known for his rigorous research on abuse liability of substances including alcohol, benzodiazepines, caffeine, tobacco, and psychedelics. This review, authored by his former mentees and collaborators, describes his methodical approach to research, his inclusive and collegial mentoring style, and his role in advancing scientific methods for abuse liability assessment, policy, and regulation. His work culminated in the establishment of the Johns Hopkins Center for Psychedelic and Consciousness Research, reflecting his curiosity-driven, humanity-serving science that continues to inspire innovation.

Mystical dynamics: renewal, luminous light, and ego disintegration as key features associated with mystical oneness-a psychometric analysis using the PES100 in controlled psychedelic studies

Repository for Publications and Research Data (ETH Zurich) January 1, 2026 Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.

Mystical oneness after psychedelics is linked to ego disintegration, renewal, and luminous light, and these connections intensify with higher doses. Analyzing 816 measurements from 386 healthy participants given LSD, psilocybin, mescaline, or DMT across 15 studies, researchers found dose-sensitive strong correlations between mystical oneness and luminous light and renewal, and a moderate-to-strong correlation with ego disintegration. The results support a dynamic model of mystical experience and suggest relevance for psychedelic-assisted therapy.

Psychedelics for Medicinal Use: How Will This Alter the Collective Laboratory Consciousness?

Clinical Chemistry March 7, 2023 Steven W. Cotten, Frederick G. Strathmann, Frederick S. Barrett et al.

Experts in psychedelic research, drug discovery, and regulation discuss the challenges of clinical adoption of psychedelic compounds and their impact on laboratory medicine. FDA approval of psychedelics like psilocybin, which has Phase III trials for major depressive disorder and treatment-resistant depression, would be a major milestone. Approval would require federal workplace drug testing guidelines to address new prescription drugs, potential false positives, and Medical Review Officer decisions. Laboratories must adapt by evaluating test panels, analytical ranges, and interpretive comments. Media portrayal ranges from dangerous drugs to panaceas, but regulatory decisions should rely on objective scientific data. Patients with mood and substance use disorders stand to benefit most.

Differences in personality, cognitive abilities, illicit drug use, and white matter structural integrity between hallucinogen users and matched controls

Research Square April 20, 2022 Aviv Aharon-Almagor, Frederick S. Barrett

People who have used hallucinogens show greater openness to new experiences and higher cognitive ability scores compared to non-users, along with denser structural connectivity in white matter tracts linked to cognition, emotion, and creativity. The study compared 53 hallucinogen users with 53 matched non-users from a public database, using diffusion tensor imaging and psychological assessments. Hallucinogen users also reported more lifetime use of other illicit drugs. These findings suggest hallucinogen use may be associated with lasting changes in brain structure and personality, offering clues to possible neural mechanisms behind therapeutic effects.