Research Ethics
April 2, 2025
Katherine Cheung, Rebecca Ehrenkranz, David B. Yaden
2 citations
Randomized controlled trials (RCTs) are the gold standard for showing treatment efficacy, but they alone do not prevent all bias. This paper reviews conflicts of interest and other biases that challenge methodological rigor in psychedelic RCTs, and recommends four actionable mitigation measures: independent data assessment, multisite trials, quantitative bias analysis, and open science practices. These practices are not specific to psychedelic research and could reduce bias across clinical research fields.
Wellcome Open Res
January 13, 2025
Samuel Streicher, Christopher Register, Xiu Lim et al.
2 citations
A protocol is described for a scoping review that will map ethical arguments for and against the voluntary use of psychedelics as moral bioenhancers. The review will follow the Joanna Briggs Institute methodology, searching multiple databases for published and unpublished sources that present explicit ethical arguments. Sources focused primarily on clinical treatment or unavailable in English will be excluded. Two independent raters will assess eligibility, with disagreements resolved by a third reviewer. Data will be charted and analyzed following PRISMA-ScR guidelines.
BMC Psychol
July 1, 2024
Julia S Rohde, Sean P. Goldy, Marianna Graziosi et al.
2 citations
A Christian contemplative practice, centering prayer, can reduce stress and improve well-being. An online intervention study found that participants who practiced centering prayer reported lower stress levels and greater flourishing compared to a control group. The practice involves silent, intentional focus on God's presence, promoting inner calm and emotional balance. These findings suggest that incorporating this spiritual discipline into daily life may offer mental health benefits, including stress relief and enhanced personal growth.
JAMA Psychiatry
December 6, 2023
David B. Yaden, Natalie Gukasyan, Sandeep M. Nayak
2 citations
No Summary
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%).
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Katherine Cheung, Rebecca Ehrenkranz, Jared T. Hinkle et al.
1 citation
A commentary responds to a proposed framework for assessing adverse events in psychedelic-assisted therapies, which includes spiritual, existential, religious, and theological impacts. The authors argue that adverse event assessment in psychedelic clinical trials should match the rigor and standards of other research areas, and emphasize the need for transparency and accessibility in reporting. The commentary discusses the framework's feasibility and various assessment methods, focusing on ensuring systematic and unbiased evaluation of adverse events.
June 9, 2023
Sandeep M. Nayak, Sydney H White, Samantha Hilbert et al.
1 citation
preprint
A longitudinal study of 657 people planning a psychedelic experience measured changes in beliefs about mind perception, metaphysical positions, and Atheist-Believer status before and after the experience. Replicating prior work, participants showed increased mind perception for living and non-living targets such as plants and animals. However, there was little to no change in metaphysical beliefs like dualism or in Atheist-Believer status. These results contrast with cross-sectional studies suggesting psychedelics alter non-naturalistic beliefs or religious identity, but they support the idea that psychedelics specifically affect how people perceive minds in various entities.
October 28, 2022
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
1 citation
preprint
Serotonergic antidepressants, such as SSRIs and SNRIs, weaken psilocybin's effects, while the non-serotonergic antidepressant bupropion has less of a dampening effect. In 595 reports of taking psilocybin with an antidepressant, the probability of weaker than expected effects was 0.48 for SSRIs, 0.56 for SNRIs, and 0.29 for bupropion. After discontinuing a serotonergic antidepressant, reduced psilocybin effects persisted for up to 3 months, with odds of reduced effects not significantly different from the first week until 3–6 months post-discontinuation. The findings suggest that serotonergic antidepressants diminish psilocybin's effects both concurrently and for months after stopping.
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
International Journal of Drug Policy
June 13, 2026
Katherine Cheung, Caleigh Propes, David B. Yaden
Oregon's psilocybin services program, established under the Psilocybin Services Act, allows adults over 21 to access psilocybin at licensed service centers with facilitator supervision but without a medical referral or clinical oversight. Analysis of the first full year of Oregon Health Authority data shows reported adverse reactions were relatively uncommon in 2025, though the reporting framework sets a high threshold for reportable events. Access remains limited, with most clients being high-income and from outside Oregon. The program has expanded supervised psilocybin use beyond strictly medical uses, with some clients using services for general wellness and others for depression or anxiety. The authors argue that broad eligibility criteria and supervision requirements may raise safety concerns, especially for clients with clinical symptoms.
Psychopharmacology
May 28, 2026
Mazen A Atiq, Eli Weisman, Rodrigo B Guerra et al.
A healthy 35-year-old man experienced a rare hypotensive adverse event—neurocardiogenic syncope (fainting)—about 60 minutes after taking 25 mg of oral psilocybin in a clinical trial. His blood pressure dropped to 93/51 mmHg, with rapid heart rate and sweating, but he stabilized quickly with leg elevation and oral hydration. The episode may have been triggered by upright seated posture, restrictive EEG equipment, and anxiety about upcoming transcranial magnetic stimulation. Fewer than one-quarter of contemporary psychedelic trials report systematic adverse event assessment, highlighting the need for transparent documentation of both hypertensive and hypotensive events as psilocybin moves toward potential FDA approval.
Accountability in research
May 1, 2026
Katherine Cheung, Rebecca Ehrenkranz, Brian D. Earp et al.
Several proposals across fields suggest including independent actors in research to manage bias, such as independent auditors for adverse events in psychedelic science or independent researchers in trial teams. However, the concept of independence is often undefined. While introducing independent actors seems beneficial for reducing bias and improving rigor, it may also have significant drawbacks. The authors argue that the implicit sense of independence is freedom from influences that could reduce the trustworthiness or accuracy of findings. They explore whether such actors can be identified without trade-offs with other scientific goals, like expertise. Two models from law and science are offered to guide incorporation of independent actors.
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.
medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.
American Journal of Bioethics
January 1, 2026
Katherine Cheung, Brian D. Earp, Kyle Patch et al.
No Summary
Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Frederick S. Barrett, Suzette M Evans et al.
Roland R. Griffiths was a highly influential scientist in behavioral and neuropsychopharmacology, known for his rigorous research on abuse liability of substances including alcohol, benzodiazepines, caffeine, tobacco, and psychedelics. This review, authored by his former mentees and collaborators, describes his methodical approach to research, his inclusive and collegial mentoring style, and his role in advancing scientific methods for abuse liability assessment, policy, and regulation. His work culminated in the establishment of the Johns Hopkins Center for Psychedelic and Consciousness Research, reflecting his curiosity-driven, humanity-serving science that continues to inspire innovation.
medRxiv Preprint Server
December 5, 2025
Gabriel Loewinger, Mats J. Stensrud, Sandeep M. Nayak et al.
preprint
Functional unmasking (unblinding) in clinical trials for mental health treatments, especially with psychedelics, can bias results because participants often know they received the active drug due to its unmistakable acute effects. This undermines confidence that outcomes reflect true therapeutic properties rather than placebo-like effects. A counterfactual conceptualization formalizes the shortcomings of existing solutions like dose-response and active controls, and shows how modern causal inference approaches can isolate effects free of this contamination. Feedback mechanisms between perceived benefits and expectancies can make traditional methods obscure or exaggerate therapeutic benefits. The proposal motivates trial designs and statistical methods to mitigate the impacts of functional unmasking.
November 25, 2024
Joshua Maurice Kugel, Ruben Laukkonen, David B. Yaden et al.
preprint
Insights—sudden, subjectively true understandings—are common during psychedelic experiences and are often considered central to therapy, but their role had not been systematically assessed. This systematic review of 98 studies found that psychedelic-catalyzed insight (PCI) was positively correlated with dose and was statistically significant in 93% of studies comparing psychedelic to placebo. Crucially, 86% of studies found PCI associated with positive therapeutic outcomes, often more strongly than mystical-type experiences. The findings suggest PCI is an important topic for clinical psychedelic therapy and for understanding mechanisms of psychedelic therapy.
August 31, 2022
David B. Yaden, Andrew B. Newberg
Numinous experience, the feeling of being in touch with divinity or God, is the most prevalent kind of spiritual experience people report, according to the authors' research data. This chapter of Part II examines numinous experience as part of a typology of spiritual experiences, describing William James's perspective on it, followed by contemporary scholarship and psychological research on both pathological and positive aspects, and concludes with neuroscience research on this type of experience.
General Hospital Psychiatry
January 1, 2026
Jonathan R Schettino, Katherine Cheung, Sandeep M. Nayak et al.
A debate exists in psychedelic research about whether the interpersonal interactions with participants before, during, and after acute drug effects should be called 'psychological support' (focused on safety) or 'psychotherapy' (also aiming for efficacy). The authors propose definitions and criteria for both forms, then test them on 11 published classic psychedelic clinical trials. Their procedure categorized 10 of 11 studies as more consistent with one label or the other, but achieved clear distinctions in only 4 studies. They argue that higher-quality data on the interpersonal interaction is needed to distinguish the two, and suggest ways their criteria can be used to empirically test the relative safety and efficacy of psychological support versus psychotherapy in psychedelic medicine.
The Varieties of Spiritual Experience
October 15, 2022
David B. Yaden, Andrew B. Newberg
Mystical experiences involve an intensely felt fading of the sense of self and/or feelings of increased connectedness, up to a sense of complete unity. In ordinary consciousness, there is a distinction between self and everything else, but during such experiences the sense of self can fade and become part of everything else. Neuroimaging of meditators and nuns shows that brain regions that differentiate self from the world are inhibited during these experiences.
The Varieties of Spiritual Experience
October 15, 2022
David B. Yaden, Andrew B. Newberg
Spiritual experiences can be triggered by a variety of scientifically identified factors, including specific circumstances, personal dispositions, mindsets, rituals, practices, and psychoactive substances like psychedelics. Future neurotechnologies may also play a role. This chapter, drawing on the Jamesian approach of setting aside theological questions, summarizes research on the conditions that make such experiences more likely to occur.
The International journal on drug policy
December 1, 2021
David B. Yaden, Andrea P Berghella, Paul S. Regier et al.
Classic psychedelics like psilocybin show promise for treating substance use disorders, and if larger trials confirm efficacy, psychedelic-assisted psychotherapy might be integrated into existing treatments such as cognitive behavioral therapy and twelve-step facilitation programs like Alcoholics Anonymous. Although AA has historically rejected medication-assisted treatments, the authors argue that classic psychedelics and their subjective experiences may be more compatible than conventional medications. They describe Bill Wilson's, the founder of AA, little-known experiences with psychedelics, suggesting aspects of psychedelic treatments could complement AA. A review of clinical trials evaluating psychedelics for substance use disorders is provided, along with discussion of potential large-scale impact if integrated into AA.