JAMA
August 31, 2023
Charles L. Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
Contemporary Clinical Trials
December 1, 2022
Kelley C O'Donnell, Sarah E. Mennenga, Lindsey T. Owens et al.
24 citations
Classic psychedelics like psilocybin may help people change their behavior in substance use disorders. This paper describes the protocol for a multi-site, double-blind, randomized controlled trial that tested psilocybin-assisted psychotherapy in 96 alcohol-dependent volunteers. Participants received either psilocybin or an active placebo (diphenhydramine) during two dosing sessions, alongside a structured 12-week psychotherapy platform. The primary outcome was the proportion of heavy drinking days over 32 weeks after the first dose. Secondary outcomes included safety, abstinence, craving, and self-efficacy. The primary results are reported elsewhere; this paper focuses on the rationale and design decisions.
Journal of Affective Disorders
September 1, 2022
David S. Mathai, Scott M Lee, Victoria Mora et al.
16 citations
Informed consent documents from 23 American ketamine clinics for psychiatric treatment cover most required elements but vary greatly in detail. Key gaps include poor communication about long-term side effects, alternative treatments, pre-treatment evaluations, support during treatment, psychological interventions, and dissociative effects. All forms are written at a readability level too high for many patients. The findings suggest that both patients and providers would benefit from more deliberate, evidence-informed consent processes to support shared decision-making as off-label ketamine use expands.
Psychedelic Med (New Rochelle)
December 13, 2023
Kelley C O'Donnell, Daniel E. Roberts, Terence H. W. Ching et al.
13 citations
The term 'psychedelic' carries multiple, sometimes conflicting, meanings across different contexts—scientific, cultural, legal, and historical. This ambiguity can hinder clear communication and slow research progress by creating misunderstandings among researchers, clinicians, policymakers, and the public. The authors argue that recognizing and clarifying these varied definitions is essential for advancing the field, as precise language helps align expectations, improve study reproducibility, and inform policy decisions. Without shared understanding, efforts to study and apply psychedelics therapeutically risk confusion and fragmentation.
PsyArXiv
March 26, 2026
Broc A. Pagni, Stephen Ross, Sarah E. Mennenga et al.
preprint
An open-label extension of a Phase II randomized controlled trial examined the safety and efficacy of psilocybin-assisted therapy for alcohol use disorder. Participants who had received either psilocybin or placebo in the main trial were offered two open-label psilocybin sessions. The treatment was well tolerated, with no serious adverse events attributed to psilocybin. Heavy drinking days decreased substantially from baseline, and the reduction was sustained through the 32-week follow-up. The findings suggest that psilocybin-assisted therapy may produce durable reductions in alcohol consumption among individuals with alcohol use disorder.
Frontiers in Psychology
January 1, 2024
Kelley C O'Donnell, Lauren Okano, Michael Alpert et al.
A conceptual framework for MDMA-Assisted Therapy for PTSD centers on the participant's inner healing intelligence as the primary agent of change, with the therapeutic relationship as the core facilitative condition. This inner-directed, holistic, self-directed, relational, and trauma-informed approach includes a non-pathologizing stance toward embodied experiences, such as intense emotional expression, multiplicity, suicidal ideation, and transpersonal experiences. Therapists bring psychodynamic, somatic, and transpersonal awareness, empathic attunement, relational skillfulness, and cultural humility. MDMA with this psychotherapy outperformed placebo with psychotherapy in Phase 2 and 3 trials, though significant symptom reduction also occurred in the placebo group, supporting the psychotherapy model itself.
Kelley C O'Donnell, Michael Alpert, Lauren Okano et al.
preprint
MDMA-Assisted Therapy for PTSD uses a short-term, intensive psychotherapy model that includes three sessions facilitated by MDMA along with non-drug therapy sessions. The MDMA helps recall and process traumatic memories and enhances learning in social contexts, integrating top-down and bottom-up trauma care. This paper describes the psychotherapeutic concepts and theories behind this approach, centering on the participant's inner healing intelligence as the main agent of change, with the therapeutic relationship as a core facilitative condition. Phase 2 and 3 trials showed MDMA with therapy outperformed placebo with therapy in reducing PTSD symptoms, though significant symptom reduction also occurred in participants who received only therapy.