Journal of Psychopharmacology
November 30, 2016
Stephen Ross, Anthony P. Bossis, Jeffrey Guss et al.
1,699 citations
A single moderate dose of psilocybin (0.3 mg/kg), combined with psychotherapy, produced immediate and sustained improvements in anxiety and depression among 29 patients with cancer-related psychological distress. At the 6.5-month follow-up, approximately 60–80% of participants continued to show clinically significant reductions in depression or anxiety. Psilocybin also decreased demoralization and hopelessness, improved spiritual wellbeing, quality of life, and attitudes toward death. The therapeutic effects on anxiety and depression were mediated by the psilocybin-induced mystical experience.
JAMA Psychiatry
August 24, 2022
Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt et al.
668 citations
Two doses of psilocybin, given alongside psychotherapy, substantially reduced heavy drinking in people with alcohol use disorder compared to an active placebo (diphenhydramine) plus psychotherapy. Over 32 weeks, heavy drinking days averaged 9.7% in the psilocybin group versus 23.6% in the placebo group—a mean difference of 13.9 percentage points. Daily alcohol consumption was also lower with psilocybin. No serious adverse events occurred in the psilocybin group. The findings support further research into psilocybin-assisted treatment for alcohol use disorder.
Journal of Psychopharmacology
January 9, 2020
Gabrielle Agin-Liebes, Tara C. Malone, Matthew M. Yalch et al.
353 citations
A long-term follow-up of a randomized trial found that psilocybin-assisted psychotherapy produced lasting reductions in anxiety, depression, hopelessness, demoralization, and death anxiety in people with cancer-related psychiatric distress. At an average of 3.2 and 4.5 years after psilocybin administration, 60–80% of participants still showed clinically significant antidepressant or anxiolytic responses. Most participants (71–100%) attributed positive life changes to the therapy and rated it among the most personally meaningful and spiritually significant experiences of their lives. The study's conclusions are limited by the crossover design of the original trial, but the results suggest psilocybin-assisted therapy may promote long-term relief from cancer-related distress.
ACS Pharmacology & Translational Science
March 18, 2021
Stephen Ross, Gabrielle Agin-Liebes, Sharon L. Lo et al.
133 citations
People with advanced cancer face elevated risks of desire for hastened death, suicidal ideation, and completed suicide. Loss of meaning, a component of demoralization, predicts these outcomes. In a randomized controlled trial, psilocybin-assisted psychotherapy produced rapid and sustained improvements in depression, demoralization, and hopelessness. Secondary analyses showed that among participants with elevated suicidal ideation at baseline, reductions in suicidal ideation appeared as early as 8 hours and persisted for 6.5 months. Large reductions in loss of meaning emerged 2 weeks after treatment and remained significant at 6.5 months and at 3.2 and 4.5 year follow-ups. The findings suggest psilocybin-assisted psychotherapy may be an effective antisuicidal intervention for cancer patients due to its positive impact on hopelessness and meaning-making.
Frontiers in Pharmacology
April 3, 2018
Tara C. Malone, Sarah E. Mennenga, Jeffrey Guss et al.
128 citations
Cancer patients who receive psilocybin-assisted psychotherapy often have personalized experiences that extend beyond their diagnosis, centering on self-compassion, love, acceptance of death, and past trauma. In a double-blind trial, 29 patients with cancer-related anxiety and depression received either psilocybin or niacin with psychotherapy. Psilocybin produced rapid and lasting reductions in anxiety and depression. Detailed accounts of four participants show that while the content of each psilocybin session was unique, common themes emerged. The findings highlight how the subjective effects of psilocybin can address individual spiritual and psychological needs.
Frontiers in Pharmacology
February 20, 2018
Michael P. Bogenschutz, Samantha K. Podrebarac, Jessie H. Duane et al.
125 citations
After a 40-year pause, clinical research on classic hallucinogens for addiction has resumed. An ongoing double-blind placebo-controlled trial tests psilocybin-assisted treatment for alcohol use disorder, building on a small open-label feasibility study. Descriptive case studies of three participants illustrate treatment trajectories. Pivotal moments during psilocybin sessions are individualized, vivid, and memorable, often extending beyond the clinical problem. Participants experienced lasting shifts in self-perception, consciousness, and relationship with alcohol. Experiences of catharsis, forgiveness, self-compassion, and love were as salient as mystical content. Feelings of increased mindfulness, spaciousness, and control over choices and behavior were reported. The treatment elicits highly variable experiences that appear to meet individual needs.
Spirituality in Clinical Practice
September 1, 2021
Samantha K. Podrebarac, Kelley C. O’donnell, Sarah E. Mennenga et al.
38 citations
No Summary
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.
American Journal of Psychiatry
January 1, 2025
Noam Goldway, Snehal Bhatt, Stephen Ross et al.
23 citations
Psilocybin-assisted therapy (PAT) produced lasting changes in personality, indicating a normalization of abnormal personality trait expression in people with alcohol use disorder. The findings suggest that PAT may reduce impulsiveness, or that impulsive individuals may inherently respond better to the therapy. Further research is needed to clarify the mechanism.
Journal of Psychedelic Studies
September 1, 2019
Kelley C. O’donnell, Sarah E. Mennenga, Michael P. Bogenschutz
15 citations
Designing rigorous clinical trials of psilocybin for major depressive disorder requires careful attention to participant selection, placebo control, blinding, dosing, non-pharmacological support, outcome measures, and safety. Transparent methods and analysis maximize the chance of obtaining meaningful, reproducible results and help gain broader scientific acceptance for psychedelic research.
Frontiers in Neuroscience
March 13, 2023
Candace R. Lewis, Matthew S. Mcmurray, Sarah E. Mennenga et al.
3 citations
No Summary
Research Square
November 5, 2025
Sarah E. Mennenga, Toni J. Hanson, Moira G. Semple et al.
2 citations
Psilocybin reverses age-related behavioral and epigenetic alterations in aged mice. Male and female C57BL/6 mice (11 months old) received two doses of psilocybin (1mg/kg) or saline one week apart. Psilocybin improved learning and memory in females and reduced depressive-like behavior across sexes. Genome-wide DNA methylation profiling in the prefrontal cortex and hippocampus revealed widespread, sex- and region-specific effects, with the right hippocampus of females showing the most extensive gene-level changes. Differentially methylated loci were enriched for pathways related to synaptic organization, axon guidance, and neuroimmune signaling.
bioRxiv Preprint Server
July 3, 2025
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
1 citation
preprint
Psychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.
Translational Psychiatry
July 11, 2026
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.
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.