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Frederick S. Barrett

Johns Hopkins University, Behavioral Pharma (United States)

53 papers in the library · 4,822 citations · publishing 2014-2026

Papers

The factor structure of the Mystical Experience Questionnaire (MEQ): Reply to Bouso et al., 2016.

Hum Psychopharmacol January 1, 2017 Frederick S. Barrett, Roland R. Griffiths 12 citations

The factor structure of the Mystical Experience Questionnaire (MEQ) is defended against critiques by Bouso et al. (2016). The authors argue that the MEQ's multi-factor model, which captures dimensions such as ineffability and mystical encounter, remains a reliable and valid tool for measuring spiritual experiences. They contend that the proposed alternative structure does not better represent the underlying facets of mystical phenomena and that the original model demonstrates consistent psychometric properties across studies. The reply emphasizes the questionnaire's effectiveness in assessing deep spiritual phenomena and maintains that its current structure is supported by empirical evidence.

Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports

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.

A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of 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.

Learned Helplessness As a Potential Transdiagnostic Therapeutic Mechanism of Classic Psychedelics

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.

An international mega-analysis of psychedelic drug effects on brain circuit function

Nature Medicine April 1, 2026 Manesh Girn, Manoj K. Doss, Leor Roseman et al. 8 citations

Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.

Psychedelics Align Brain Activity with Context

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.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis

medRxiv September 8, 2023 Patrick H. Finan, Carly Hunt, Michael L. Keaser et al. 6 citations preprint

A brief Savoring Meditation intervention, compared to Slow Breathing, reduced experimental pain intensity ratings in patients with rheumatoid arthritis. It increased cerebral blood flow in the ventromedial prefrontal cortex and connectivity between that region and the caudate during painful thermal stimulation. Participants also reported increased positive emotions and reduced anhedonic symptoms from before to after the intervention. These results suggest that Savoring Meditation engages reward-related brain circuits during pain, which may inform future work on clinical pain outcomes.

Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory

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.

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 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

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.

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.