ACS Pharmacol Transl Sci
December 10, 2020
David B. Yaden, Roland R. Griffiths
534 citations
Classic psychedelics induce altered states of consciousness that people often find meaningful. In human studies, when the overall intensity of drug effects is statistically controlled, specific subjective experiences—not just neurobiological changes—predict therapeutic and other positive outcomes. The authors argue that these subjective effects are necessary for lasting benefits and account for most of the improvement, while underlying brain mechanisms are likely necessary but insufficient on their own.
JAMA Psychiatry
October 1, 2022
David B. Yaden, James B. Potash, Roland R. Griffiths
153 citations
Public perception of psychedelics has swung from extreme stigma to uncritical enthusiasm, creating obstacles for clinical application. This viewpoint argues that both poles are problematic and advocates for continued scientific study while encouraging critical examination of claims not supported by evidence. The authors call for a balanced approach that neither dismisses therapeutic potential nor overpromises benefits, emphasizing the need for rigorous research to guide responsible clinical integration.
JAMA Psychiatry
September 4, 2024
Marianna Graziosi, Jared T. Hinkle, Sandeep M. Nayak et al.
126 citations
Classic psychedelics such as LSD and psilocybin are generally well tolerated in clinical or research settings, though serious adverse events do occur. In a systematic review and meta-analysis of 214 studies, serious adverse events were reported for no healthy participants and for about 4% of participants with preexisting neuropsychiatric disorders, including worsening depression, suicidal behavior, psychosis, and convulsive episodes. Nonserious adverse events requiring medical intervention, such as paranoia and headache, were rare. In contemporary research, no deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders were reported after high-dose psychedelic administration. However, the quality of adverse event monitoring and reporting varied significantly across studies.
Journal of Humanistic Psychology
October 24, 2016
David B. Yaden, Khoa D. Le Nguyen, Margaret L. Kern et al.
125 citations
Religious, spiritual, or mystical experiences triggered by psychedelic substances are rated as more intensely mystical and produce a reduced fear of death, a greater sense of purpose, and increased spirituality compared to similar experiences arising through other means. These findings held even after controlling for gender, education, socioeconomic status, and religious affiliation. The results support the view that psychedelic-induced experiences are genuinely mystical and generally positive in outcome.
Frontiers in Psychology
May 23, 2022
David B. Yaden, Dylan Earp, Marianna Graziosi et al.
106 citations
The acute effects of psychedelics depend on users' expectations and surroundings (set and setting). Current clinical psychedelic administration draws on indigenous practices, 1960s new age spirituality, psychodynamic approaches, and cognitive-behavioral therapies. Cognitive-behavioral therapies, including acceptance and commitment therapy (ACT), have the strongest rationale for psychedelic-assisted psychotherapy because they avoid cultural insensitivity, make minimal speculative assumptions about the mind and reality, and have the largest empirical support for safety and effectiveness outside psychedelic therapy. Concepts from CBT, DBT, and ACT can usefully inform preparation, session, and integration phases. Evidence-based psychotherapeutic paradigms provide the best starting point for safety and efficacy.
JAMA Psychiatry
May 1, 2021
David B. Yaden, Mary E. Yaden, Roland R. Griffiths
102 citations
No Summary
Journal of psychopharmacology (Oxford, England)
January 1, 2023
Sandeep M. Nayak, Manvir Singh, David B. Yaden et al.
87 citations
A survey of 2374 people who reported a belief-changing psychedelic experience found that a single experience increased non-physicalist beliefs, including dualism, paranormal/spirituality, and consciousness in both mammals and non-mammals, with medium to large effects. Beliefs in superstition changed negligibly. The percentage identifying as a believer in a higher power or ultimate reality rose from 29% before to 59% after the experience. Greater mystical experiences during the psychedelic session were linked to larger belief shifts. These changes persisted an average of 8.4 years later.
August 18, 2022
David B. Yaden, Andrew B. Newberg
80 citations
Spiritual experiences have been reported worldwide throughout history, including the present day. Founders of major religions, philosophers since ancient Greeks, and about 30% of people in the United States and United Kingdom report them. William James analyzed these experiences a century ago, raising questions about triggers, brain and body effects, and lasting impacts. This book explores modern scientific breakthroughs from psychology and neuroscience, inviting readers into laboratories to learn research methods. It includes survey questions for classifying experiences and diverse personal accounts. Building on James's foundation, it provides a scientifically informed contemporary understanding of these profound, often life-meaningful events.
Psychology of Religion and Spirituality
July 27, 2015
David B. Yaden, Johannes C. Eichstaedt, H. Andrew Schwartz et al.
68 citations
People who report having had mystical experiences use language that is more socially and spatially inclusive—words like 'close,' 'we,' and 'with'—and fewer overtly religious terms such as 'prayed,' 'Christ,' or 'church' compared to those who have not had such experiences. This pattern emerged from quantitative linguistic analysis of 777 participants' written accounts of their most significant spiritual or religious experience. The findings suggest that mystical experiences, though often described as ineffable, can be meaningfully communicated, and that language analysis offers a way to study them.
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.
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.
JAMA Network Open
June 3, 2024
Amy L. Mcguire, I Glenn Cohen, Dominic Sisti et al.
41 citations
A consensus statement from a 2023 meeting of 27 experts identifies 20 points of consensus across five ethical issues for integrating psychedelic medicines into mainstream medical practice: reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping. The meeting included clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists. The statement focuses on government-approved medical use in the US and abroad, emphasizing that policymakers must address challenges ahead while acknowledging the hopeful moment.
Psychopharmacology
April 1, 2023
David S. Mathai, Sandeep M. Nayak, David B. Yaden et al.
36 citations
For esketamine, a form of ketamine used for treatment-resistant depression, there is no clinically meaningful link between how dissociated a person feels during the drug experience and how much their depression improves. Analyzing data from 576 participants across two clinical trials, researchers measured dissociation with the Clinician-Administered Dissociative States Scale (CADSS) and depression with the Montgomery-Åsberg Depression Rating Scale (MADRS). A statistical model found no significant interaction between dissociation and antidepressant effect over four weeks. A separate analysis showed that each additional point on the dissociation scale on day 1 was associated with a very small 0.
Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees
October 1, 2022
David B. Yaden, Brian D. Earp, Roland R. Griffiths
31 citations
Psychedelics partly achieve their therapeutic effects through the subjective experiences they produce and how individuals interpret those experiences. Because these subjective effects can be disturbing for people with certain mental illnesses, researchers are developing 'nonsubjective' psychedelics that cause similar biological changes without the characteristic subjective effects. The authors broadly support creating such substances for scientific and clinical reasons but argue they should be reserved only for cases where subjective effects are specifically contraindicated. Classic psychedelics that produce subjective experiences should remain the default standard of care, as withholding typically positive, meaningful, and therapeutic experiences from most patients raises ethical concerns.
Current Topics in Behavioral Neurosciences
January 1, 2022
David B. Yaden, Sandeep M. Nayak, Natalie Gukasyan et al.
31 citations
End-of-life and palliative care have improved, but psychopharmacological options for depression, existential distress, and well-being remain limited. This review examines recent clinical research on psychedelics for patients with life-threatening diagnoses and proposes that psychedelics could offer clinicians an additional treatment option in end-of-life and palliative care settings.
The American journal of bioethics : AJOB
January 1, 2025
Katherine Cheung, Brian D. Earp, Kyle Patch et al.
30 citations
The authors argue against the idea that psychedelics raise uniquely exceptional ethical issues in clinical medicine, comparing this position to earlier debates about genetic exceptionalism in bioethics. They contend that psychedelics share more commonalities with existing medical interventions than is often assumed, and that adopting a stance of "psychedelic ethical exceptionalism" carries risks. Instead, they propose that consistent ethical rules and evidentiary standards should apply across all relevant areas of clinical medicine. While changes to existing standards may be warranted, such changes should not be justified by appealing to the alleged uniqueness of psychedelics.
Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees
June 27, 2023
Katherine Cheung, Kyle Patch, Brian D. Earp et al.
27 citations
Psychedelics like psilocybin produce altered states of consciousness that change perception, cognition, and affect. They show promise as therapeutic agents combined with talk therapy for conditions such as major depression and substance use disorder. It remains unclear whether these acute subjective effects are necessary for therapeutic benefits. This uncertainty has sparked debate about whether psychedelics without subjective effects could still have therapeutic impact, or whether the subjective effects are essential for full therapeutic realization.
Psychoactives
April 16, 2024
Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al.
26 citations
Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.
Frontiers in Psychology
May 23, 2022
Tomas Frymann, Sophie Whitney, David B. Yaden et al.
26 citations
Two new psychometric scales, the Integration Engagement Scale (IES) and the Experienced Integration Scale (EIS), were developed to measure different aspects of psychedelic integration—the period after acute drug effects. The IES captures positive behavioral engagement with integration, while the EIS captures internal feelings of being integrated. Scale items were refined with input from experts and clinicians using the Iterative Process Model. Content validity, internal structure, and reliability were assessed through expert surveys, cognitive interviewing, convergent validity analysis, exploratory and confirmatory factor analysis. The data indicate the scales are valid and reliable measures of behavioral and experiential forms of psychedelic integration.
Journal of Psychoactive Drugs
January 1, 2023
Julian Urrutia, Brian T Anderson, Sean J Belouin et al.
21 citations
Combining psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems in integrative, community-based models of care could transform global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that positively affect health, well-being, and prosocial behavior, and combining them appears synergistic. Traditional knowledge systems offer ethnobotanical expertise and time-tested practices. A decolonized agenda for psychedelic research requires collaborative engagement with traditional knowledge stewards to co-develop evidence-based integrative care accessible to their communities. Health systems could include Indigenous and traditional healers as stakeholders in designing, implementing, and evaluating community-based approaches for safely scaling psychedelic treatments.
Religion Brain & Behavior
March 22, 2017
Andrew B. Newberg, Nancy Wintering, David B. Yaden et al.
19 citations
A seven-day spiritual retreat involving meditation and prayer led to measurable changes in brain chemistry. After the retreat, dopamine transporter binding decreased in the basal ganglia and serotonin transporter binding decreased in the midbrain, suggesting altered neurotransmitter activity. Participants also reported changes in psychological and spiritual measures. This preliminary study of 14 individuals provides the first neurophysiological data on such retreats, though the authors note methodological challenges for future research.
Psychiatr Res Clin Pract
February 11, 2025
Jules Evans, Marc Aixalà, Brian T Anderson et al.
18 citations
Thirty psychedelic researchers identified critical gaps in knowledge about harms from psychedelic use, including how to define those harms, predict them, and treat them effectively. They recommend better online information, peer support groups, affordable therapy, and psychiatric consultation for people experiencing post-psychedelic difficulties. The researchers also call for improved funding for a psychedelic safety net, suggesting that psychedelic philanthropists, investors, and companies commit 1% of their investment to support safety measures such as research and support services. The article outlines practical steps to make the field of psychedelic medicine safer.
Journal of Psychoactive Drugs
May 7, 2024
Sandeep M. Nayak, Sydney H White, Samantha Hilbert et al.
18 citations
A prospective longitudinal study of 657 people planning a psilocybin experience outside a laboratory found that after the experience, participants reported increased perception of minds in various living and non-living entities such as plants and rocks, replicating earlier findings. However, the study found little to no change in participants' metaphysical beliefs, such as dualism, or in their self-reported Atheist-Believer status. These results contrast with cross-sectional studies suggesting psilocybin experiences alter Atheist-Believer status and non-naturalistic beliefs, but they support the relevance of mind perception and mentalization processes.
Neuroscience and Biobehavioral Reviews
June 1, 2025
Joshua Kugel, Ruben Laukkonen, David B. Yaden et al.
15 citations
A sudden shift in understanding or perspective that feels true—called insight—is common during psychedelic experiences and is often considered central to their therapeutic value. A systematic review of 98 studies (40 survey, 58 interventional) found that insight was positively correlated with psychedelic dose and was significantly higher after psychedelics in 93% of studies comparing to placebo. Crucially, 86% of studies found that insight was associated with therapeutic improvement, and this relationship was often stronger than that of mystical-type experience. The findings suggest insight's importance for clinical practice and understanding mechanisms of psychedelic therapy, though heterogeneous study designs and possible publication bias limit meta-analytic conclusions.