Frontiers in Psychology
March 28, 2022
Sandeep M. Nayak, Roland R. Griffiths
76 citations
Among people who reported a belief-changing psychedelic experience, attributions of consciousness to a wide range of entities increased substantially. Before and after the experience, ratings of consciousness rose for non-human primates (from 63% to 83%), quadrupeds (59% to 79%), insects (33% to 57%), fungi (21% to 56%), plants (26% to 61%), inanimate natural objects (8% to 26%), and inanimate manmade objects (3% to 15%). Higher mystical experience scores predicted larger increases. These changes persisted even years later, while beliefs in free will and superstition remained unchanged. The findings suggest psychedelic experiences can durably alter how people attribute consciousness to other beings and objects.
The International Journal of Neuropsychopharmacology
June 5, 2015
Marta Valle, Montserrat Puntes, Jimena Coimbra et al.
75 citations
Salvinorin-A, a compound from the plant Salvia divinorum that activates kappa-opioid receptors, produces dose-dependent changes in perception and body awareness. In eight healthy volunteers with prior psychedelic experience, vaporized salvinorin-A at 0.25, 0.50, and 1 mg caused detachment from external reality, elaborate visions, and auditory phenomena. Lower doses increased bodily sensations, while the highest dose produced a complete loss of contact with the body. The effects on body awareness followed an inverted-U pattern, suggesting the kappa-opioid receptor plays a key role in regulating sensory perception, interoception, and the sense of body ownership.
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.
Journal of Psychopharmacology
June 8, 2023
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
60 citations
Psilocybin-containing mushrooms produce weaker drug effects in people taking SSRI or SNRI antidepressants, with a 47% probability of weaker-than-expected effects for SSRIs and 55% for SNRIs, compared to 29% for bupropion, a non-serotonergic antidepressant. This dampening effect persists for up to three months after discontinuing the antidepressant, based on retrospective survey data from over 2,000 reports. Removing responses involving fluoxetine, which has a long half-life, did not change the result. The findings suggest that serotonergic antidepressants may reduce psilocybin's effects both during use and for a period after stopping.
PLoS ONE
August 24, 2022
Mary M. Sweeney, Sandeep M. Nayak, Ethan Hurwitz et al.
60 citations
Psychedelic drug experiences and near-death or other non-ordinary experiences both change people's beliefs about death, but direct comparisons are rare. In a survey of 3,192 individuals who reported such experiences, those from non-drug causes (e.g., near-death) were more likely to involve unconsciousness, clinical death, or imminent danger. Both groups reported similar reductions in fear of death, high personal meaning, spiritual significance, and psychological insight. However, psychedelic participants scored higher on standardized measures of mystical and near-death features, while non-drug participants more often rated their experience as the single most meaningful of their lives. Among psychedelics, ayahuasca and DMT produced stronger positive enduring effects than psilocybin and LSD.
Nature Reviews Psychology
September 3, 2024
David B. Yaden, Sean P. Goldy, Brandon Weiss et al.
57 citations
No Summary
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.
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.
Sci Am
December 1, 2010
Roland R. Griffiths, Charles S. Grob
46 citations
The text briefly notes that hallucinogens are being used as medicine, indicating a shift toward therapeutic applications of these substances. It does not provide details about specific conditions, outcomes, or evidence.
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.
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.
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.
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.
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.
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.
Drug and Alcohol Dependence
June 7, 2014
Albert P. Garcia-Romeu, Matthew W. Johnson, Roland R. Griffiths
13 citations
No Summary
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.
Nature Mental Health
October 7, 2024
Petros Petridis, Jack Grinband, Gabrielle Agin-Liebes et al.
10 citations
Psilocybin-assisted psychotherapy (PAP) may treat a wider range of psychiatric symptoms in cancer patients than previously recognized. Pooled data from two phase II randomized placebo-controlled crossover trials involving 79 participants with cancer-related distress showed that PAP significantly improved anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, and somatization. No lasting phobia, paranoia, or psychosis was induced. Improvements were consistent across both trials, suggesting PAP could serve as a comprehensive mental health treatment for this population.
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.
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.
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.
Behavioural Pharmacology
August 1, 1996
Christine A. Sannerud, B. Kaminski, Roland R. Griffiths
9 citations
Intravenous self-administration of four substituted phenethylamines was evaluated in baboons trained to self-inject cocaine. High doses of MDE and N-OH-MDA maintained self-injection, while NNDMA did not reliably do so, and BDMPEA maintained self-injection in each of three baboons at one or more doses. Intermediate to high doses of all four compounds decreased food pellet intake. In some baboons, high doses of N-OH-MDA, NNDMA, and BDMPEA produced signs of behavioral toxicity similar to those of classic psychomotor stimulants, though severity and profile differed between compounds. The study documents both similarities and differences in the behavioral profiles of these phenethylamines.
Drug and Alcohol Dependence
November 1, 2015
Frederick S. Barrett, Matthew W. Johnson, Roland R. Griffiths
7 citations
No Summary
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.