About

Frederick S. Barrett is an Associate Professor of Psychiatry and Behavioral Sciences, Neuroscience, and Psychological and Brain Sciences at Johns Hopkins University School of Medicine. He serves as the Director of the Center for Psychedelic and Consciousness Research and is affiliated with the Solomon H. Snyder Department of Neuroscience. His research focuses on understanding the psychological, cognitive, and neurobiological effects of psychoactive drugs, particularly classic serotonergic psychedelics such as psilocybin and LSD, as well as atypical hallucinogens and other psychoactive compounds like stimulants and cannabinoids. Dr. Barrett employs a multidisciplinary approach, utilizing psychometrically validated questionnaires, computerized cognitive testing, electrophysiological measurements, magnetic resonance imaging, and molecular imaging to investigate these effects. His key contributions include providing empirical evidence on the effects of psilocybin on brain circuits, demonstrating its impact on cortico-striatal-thalamic-cortical circuits, and exploring its enduring effects on brain function and affect in both healthy individuals and patients with mood and substance use disorders. He was the first to show enduring effects of psilocybin on affect and brain function, as well as its antidepressant effects in clinical trials. Dr. Barrett has developed and validated instruments for assessing subjective psychedelic experiences, which are used worldwide, and has investigated how set and setting influence psychedelic experiences and their therapeutic outcomes. Additionally, he has contributed to understanding the neural basis of consciousness and subjective experiences, and has worked on computational models of music cognition, examining how music influences brain activity and behavior, especially under the influence of psychedelics. His work aims to expand knowledge on mood disorder treatments, substance use disorder therapies, and the neural mechanisms underlying consciousness.

Research topics

• Psychiatry
• Medicine
• Clinical psychology
• Internal medicine
• Psychology
• Neuroscience

Selected publications

• Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

  2025-02-13

  preprintOpen access

  Background and HypothesisVisual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation.Study DesignThis narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology.Study ResultsBoth LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Specific classes of VH in LBDs resemble those induced by SPs (e.g., illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT₂AR and 5-HT₁AR) modulation, while in LBDs, 5-HT₂AR upregulation correlates with increased VH, and its inhibition (e.g., with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation.ConclusionsExamining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between visual degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.

  PublisherDOI

• Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

  2025-07-15

  preprintOpen access

  Background and HypothesisVisual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation.Study DesignThis narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology.Study ResultsBoth LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Specific classes of VH in LBDs resemble those induced by SPs (e.g., illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT₂AR and 5-HT₁AR) modulation, while in LBDs, 5-HT₂AR upregulation correlates with increased VH, and its inhibition (e.g., with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation.ConclusionsExamining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between visual degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.

  PublisherOA PDFDOI

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

  Journal of Psychedelic Studies · 2025-09-04 · 2 citations

  articleOpen accessSenior author

  Abstract Background Major Depressive Disorder (MDD) is a leading cause of disability and economic loss, with high recurrence and treatment resistance. Psilocybin-assisted therapy (PAT) shows promise in reducing depressive symptoms, but long-term effects are unknown. We aimed to determine the long-term safety and efficacy of PAT for MDD over a five-year follow-up period. Methods Individuals who previously participated in an RCT studying the effects of PAT for patients with MDD were contacted for a long-term follow-up (LTFU) study. This study uses a parallel convergent mixed methods design. Of the original 24 RCT participants, 21 enrolled in the LTFU study, with 18 (75%) completing it. For the six non-completers, baseline scores were used in quantitative analyses as conservative estimates. The primary outcome was clinician-rated change in depression severity from baseline to LTFU. Secondary outcomes included anxiety, functional impairment, and qualitative assessments of participants' experiences and mental health. Results Significant and sustained reductions in depression were observed, with 67% in remission for at least five years post-treatment. Anxiety and functional impairment also improved. Qualitative interviews revealed lasting positive changes in mindset, emotional health, and relationships. Participants reported enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported. Conclusion This study supports the long-term efficacy and safety of PAT in reducing depressive symptoms and improving mental health in patients with MDD. Further research is needed to determine if these findings can be replicated, and to explore the mechanisms behind the sustained benefits of PAT, potentially validating an approach that could transform the treatment of MDD.

  PublisherDOI

• 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 · 2025-09-24 · 2 citations

  reviewOpen accessSenior author

  The potential for psilocybin, and other psychedelic drugs, to fulfil a much needed and potentially transformative class of psychiatric treatments has garnered significant attention. Consequently, there has been a great deal of interest and investment in accelerating its development and potential implementation in routine clinical practice. However, the expanding scope of scientific discovery, heightened media coverage, and commercial interests in the field risk outpacing the rate of developments in the necessary guidelines and infrastructure required for integration of psilocybin into clinical practice. The US National Network of Depression Centers (NNDC) Task Group on Psychedelics and Related Compounds-comprising psychiatrists, psychologists, neuroscientists, psychedelic researchers, and leaders in healthcare consulting affiliated with the NNDC-developed this consensus statement as a summary of clinical expertise and opinion on the matter, to recognise psilocybin's therapeutic potential while also emphasising the need for further research and careful consideration before the integration of psilocybin into routine clinical care. We outline the current state of the science on psilocybin, incorporating articles published through April 2025. We identify key areas for further research and frame them within the context of therapeutic and ethical implications surrounding psilocybin's use in future clinical practice. We highlight the need for further research to address gaps in understanding of therapeutic dosage, efficacy across diverse populations, and long-term safety. Finally, we propose an agenda which calls for diversification of funding, collaborative research efforts, standardised training for healthcare providers, and careful consideration of ethical dilemmas inherent in the theorised clinical use of psilocybin. Crucially, we advocate for a balanced approach that prioritises rigorous scientific standards while considering the urgency of the need for better treatment options, ensuring equitable access and safety as the field progresses. We acknowledge that the single-country focus of the NNDC may limit the generalisability of recommendations to international contexts with differing healthcare systems and regulatory landscapes.

  PublisherOA PDFDOI

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

  Psychedelic Medicine · 2025-01-20 · 7 citations

  reviewOpen access

  Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes. Methods: To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents. Results: While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research. Conclusions: Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.

  PublisherOA PDFDOI

• An international Delphi consensus for reporting of setting in psychedelic clinical trials

  Nature Medicine · 2025-06-03 · 22 citations

  articleOpen access

  Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based guidelines for reporting settings in psychedelic clinical research, according to an international group of psychedelic researchers, clinicians and past trial participants. We conducted a Delphi consensus study composed of four iterative rounds of quasi-anonymous online surveys. A total of 89 experts from 17 countries independently listed potentially important psychedelic setting variables. There were 770 responses, synthesized into 49 distinct items that were subsequently rated, debated and refined. The process yielded 30 extra-pharmacological variables reaching predefined consensus ratings:i.e., 'important' or 'very important' for ≥70% of experts. These items compose the Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines, categorized into physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. Emergent findings reveal significant ambiguities in current conceptualizations of set and setting. The ReSPCT guidelines and accompanying explanatory document provide a new standard for the design and documentation of extra-pharmacological variables in psychedelic clinical research.

  PublisherOA PDFDOI

• Psychedelics Align Brain Activity with Context

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-11 · 7 citations

  preprintOpen access

  Abstract Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are context-sensitive. To understand how this reorganisation depends on context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and naturalistic stimuli (meditation, music, and movie), before and after ingesting 19 mg of psilocybin (functional MRI ≈80 min post-dose; EEG ≈150 min post-dose). Half the participants ranked the experience among the most meaningful of their lives. Under psilocybin, functional MRI and EEG signals recorded during eyes-closed conditions became similar to those recorded during an eyes-open condition. Global functional connectivity increased in associative regions and decreased in sensory areas. Using machine learning to represent neural activity as low-dimensional trajectories, we found that psilocybin reorganised these into structured, context-sensitive patterns of brain activity that reflected both experimental condition and the quality of subjective experience, revealing an organisation that was missed by time-averaged connectivity measures. Under psilocybin, brain networks that ordinarily segregate internal and external processing coherently integrated and aligned neural dynamics with context. This context-alignment manifested as distinct and cohesive neural trajectories in participants reporting positively felt self- and boundary-dissolving effects, corresponding to the felt experience of being part of the environment, which we refer to as embeddedness —the subjective experience of being continuous with, rather than separate from, the surrounding environment. The strength of this context-alignment was associated with next-day mindset change, bridging the neural, experiential, and therapeutic dimensions of the psychedelic state. These findings show that the organisation of brain activity covaries with the experiential coherence of the psychedelic state, and provide a systems-level framework for how context-sensitive brain dynamics link neurobiology to subjective experience and behavioural change.

  PublisherOA PDFDOI

• Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

  2025-03-29

  preprintOpen access

  Background and HypothesisVisual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation.Study DesignThis narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology.Study ResultsBoth LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Specific classes of VH in LBDs resemble those induced by SPs (e.g., illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT₂AR and 5-HT₁AR) modulation, while in LBDs, 5-HT₂AR upregulation correlates with increased VH, and its inhibition (e.g., with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation.ConclusionsExamining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between visual degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.

  PublisherOA PDFDOI

• Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

  Schizophrenia Bulletin · 2025-04-17 · 2 citations

  reviewOpen access

  BACKGROUND AND HYPOTHESIS: Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; eg, Parkinson's disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; eg, psilocybin and mescaline). While these conditions differ in etiology, overlapping phenomenology, and neural mechanisms suggest shared pathways. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation. STUDY DESIGN: This narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology. STUDY RESULTS: Both LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Some features in LBDs resemble those induced by SPs (eg, illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT2AR and 5-HT1AR) modulation, while in LBDs, 5-HT2A receptor upregulation correlates with increased VH, and its inhibition (eg, with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation. CONCLUSIONS: Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between sensory degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.

  PublisherDOI

• Teaching a new dog old tricks: bringing rigor, grounding, and specificity to psychedelic neuropsychopharmacology

  Neuropsychopharmacology · 2024-08-06 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• NIH Grant R03DA042336

  NIH · $260k · 2018

Frequent coauthors

• Roland R. Griffiths

  Johns Hopkins University

  103 shared

• Matthew W. Johnson

  Johns Hopkins University

  55 shared

• Kelly E. Dunn

  University of California, San Diego

  30 shared

• George E. Bigelow

  Behavioral Pharma (United States)

  26 shared

• David A. Seminowicz

  Western University

  26 shared

• Patrick H. Finan

  University of Virginia

  23 shared

• Manoj K. Doss

  Johns Hopkins University

  21 shared

• Alan K. Davis

  The Ohio State University

  21 shared

Education

• Ph.D., Neuropsychopharmacology of Consciousness

  Johns Hopkins University School of Medicine

• M.D.

  Johns Hopkins University School of Medicine

• B.A.

  University of California, Los Angeles