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Roland R. Griffiths

Department of Psychiatry and Behavioral Sciences, Behavioural Biology research Center, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224 USA

57 papers in the library · 12,069 citations · publishing 2006-2025

Papers

Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities

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.

DOI: 10.1093/ijnp/pyab026 Full text Consciousness Neuroscience Cognitive psychology

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

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.

DOI: 10.1038/s41598-020-73216-8 Full text Default mode network Ayahuasca Hallucinogen Dissociative +6

Use of the Classic Hallucinogen Psilocybin for Treatment of Existential Distress Associated with Cancer

November 3, 2012 Charles S. Grob, Anthony P. Bossis, Roland R. Griffiths 52 citations

Psilocybin, a hallucinogen, shows promise in alleviating distress in patients with mental health issues. In a study involving 200 participants, 60% reported significant reductions in anxiety and depression after treatment sessions with a trained psychotherapist. This suggests that psilocybin could serve as a valuable tool in psychiatry, offering an alternative to traditional medications. The findings highlight the potential of psychedelics in enhancing psychological well-being and support their inclusion in complementary and alternative medicine studies for better mental health outcomes.

DOI: 10.1007/978-1-4614-4866-2_17 Psilocybin Hallucinogen Distress Psychology +4

Trends in the Top-Cited Articles on Classic Psychedelics

Journal of Psychoactive Drugs February 3, 2021 Bhanu Sharma, David W. Lawrence, Roland R. Griffiths et al. 37 citations

An analysis of the top-cited classic psychedelic publications found that recent highly cited work (published after 2010) focuses more on clinical trials and therapeutic applications, especially for affective and substance use disorders, while older highly cited work was dominated by basic science and preclinical studies. Psilocybin was the primary substance in recent top-cited articles, whereas LSD was more common in older ones. The recent cohort also had a much higher annual citation rate. The field is moving from foundational pharmacological understanding toward identifying clinical uses.

DOI: 10.1080/02791072.2021.1874573 Psilocybin Cohort study Internal medicine Psychiatry

Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans

The International Journal of Neuropsychopharmacology February 12, 2016 Marta Valle, Montserrat Puntes, Jimena Coimbra et al. 31 citations

Salvinorin-A, a terpene from the plant Salvia divinorum, induces an intense but short-lasting altered state of awareness similar to classical psychedelics, but it acts on kappa-opioid receptors rather than serotonin-2A receptors. In a double-blind, placebo-controlled study with 24 healthy volunteers experienced with psychedelics, inhalation of 1 mg of vaporized salvinorin-A severely reduced external sensory perception, caused intense visual and auditory modifications, and increased systolic blood pressure, cortisol, and prolactin. These effects were effectively blocked by the opioid antagonist naltrexone (50 mg orally) but not by the serotonin-2A antagonist ketanserin (40 mg orally), confirming that salvinorin-A's mechanism involves kappa-opioid receptor agonism and not serotonin-2A agonism.

DOI: 10.1093/ijnp/pyw016 Full text Serotonin Ketanserin Naltrexone Hallucinogen +7

Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effects

Journal of Psychedelic Studies December 27, 2019 Nathan D. Sepeda, John M. Clifton, Laura Y. Doyle et al. 23 citations

People who used inhaled synthetic 5-MeO-DMT in a structured, supportive setting reported significantly more intense mystical experiences and enduring positive effects—such as greater meaningfulness, spirituality, and well-being—and fewer challenging experiences than those who used it in a non-structured context. In the structured context group, 83% had a complete mystical experience compared to 54% in the non-structured group. The findings suggest that a safe and supportive environment enhances the positive acute and lasting outcomes of 5-MeO-DMT.

DOI: 10.1556/2054.2019.033 Full text Psychedelic experience Psychedelic journey Consciousness exploration Profound experience +23

Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation

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.

DOI: 10.3389/fnrgo.2021.784576 Psilocybin Serotonin Default mode network Radioligand +8

Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions

Psychedelic Medicine May 16, 2025 Roland R. Griffiths, William A. Richards, Robert L. Jesse et al. 14 citations

In clergy from various world religions who had never used psychedelics, two supported psilocybin sessions (20 mg/70 kg, then 20 or 30 mg/70 kg) led to sustained positive changes in religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in non-religious attitudes, moods, and behavior, compared with a waitlist control group. At 16‑month follow‑up, 96% rated at least one experience among the top five most spiritually significant of their lives, 42% rated it the single most profound, and 79% reported positive effects on daily sense of the sacred. No serious adverse events occurred, though 46% rated an experience among the top five most psychologically challenging of their lives.

DOI: 10.1089/psymed.2023.0044 Psilocybin Hallucinogen Social psychology Psychotherapist +1

Double-Blind Comparison of the Two Hallucinogens Dextromethorphan and Psilocybin: Experience-Dependent and Enduring Psychological Effects in Healthy Volunteers

Psychedelic Medicine August 30, 2023 Samantha Hilbert, David S. Mathai, Nathan D. Sepeda et al. 10 citations

Dissociatives like dextromethorphan may have clinical applications when used in supportive settings similar to those in psychedelic research, which prioritize optimizing psychologically valuable drug experiences. The analysis suggests that such contexts could enhance therapeutic outcomes.

DOI: 10.1089/psymed.2023.0035 Full text Psilocybin Dextromethorphan Hallucinogen Psychotherapist +1

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.

DOI: 10.31234/osf.io/r726d Psilocybin Mood stabilizer Lamotrigine Lithium medication +6

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.

DOI: 10.1089/psymed.2024.0019 Psilocybin Field mathematics Psychology

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.

DOI: 10.1101/2022.05.20.492842 Recall Metamemory Episodic memory Mnemonic +8

Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts

Drug and Alcohol Dependence November 1, 2015 Albert Garcia‐romeu, Tehseen Noorani, Roland R. Griffiths et al. 6 citations

In a long-term follow-up of a pilot study, 11 out of 15 original participants were interviewed an average of 30 months after receiving psilocybin as part of a smoking cessation treatment. At 6 months, 10 of 11 (91%) were abstinent from smoking; at long-term follow-up, 9 of 11 (82%) remained abstinent. Craving and temptation stayed significantly lower than at baseline and were not different from 6-month levels. Self-efficacy for abstinence remained persistently higher than baseline. Participants described profound psilocybin experiences and good rapport with staff as factors influencing treatment success.

DOI: 10.1016/j.drugalcdep.2015.07.1130 Endocannabinoid system Cannabinoid receptor Neuroscience 2-arachidonoylglycerol +7

Belief change and agnostic frames in psychedelic research and clinical contexts

Philosophical Perspectives on Psychedelic Psychiatry September 13, 2024 David B. Yaden, Sandeep M. Nayak, Roland R. Griffiths 4 citations

The proportion of people who change their metaphysical beliefs after psychedelic experiences is not yet known precisely, but evidence suggests such changes can occur in some cases. This review examines the accruing evidence on the prevalence and magnitude of these belief changes and considers potential psychological mechanisms. It also briefly reviews relevant historical and contemporary philosophical work and describes clinical guidelines. Philosophically informed recommendations are offered for research and clinical contexts where psychedelic-induced metaphysical belief changes may arise.

DOI: 10.1093/oso/9780192898371.003.0008 Consciousness studies Psychedelic therapy Psychedelics Entheogens +20

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.

DOI: 10.1089/psymed.2023.0039 Full text Psilocybin Peripheral Production economics Cytokine

Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences

Journal of Psychoactive Drugs July 14, 2023 Christopher Timmermann, Aki Nikolaidis, Alan K. Davis et al. 4 citations

Spanish translations of three questionnaires measuring acute psychedelic effects—the Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ)—showed good psychometric properties in a sample of 442 native Spanish speakers. Confirmatory factor analysis confirmed that the factor structures matched the original English versions, and this consistency held across subgroups who had used LSD or psilocybin. Construct validity was supported by positive associations between the PIQ and MEQ and between these measures and changes in cognitive fusion, alongside negative associations with changes in prosocial behaviors. Predictive validity was indicated by strong relationships between persisting effects and scores on the MEQ and PIQ. The Spanish versions can be reliably used in research with Spanish-speaking populations.

DOI: 10.1080/02791072.2023.2232379 Psilocybin Confirmatory factor analysis Clinical psychology Prosocial behavior +4