Journal of Palliative Medicine
October 1, 2023
Noah D Gold, Austin J. Mallard, Jacob C Hermann et al.
5 citations
Psychedelic-assisted psychotherapy (PAP) may help alleviate psychiatric and existential distress in people with amyotrophic lateral sclerosis (ALS), a terminal neurodegenerative disease with an average survival of 3-4 years. The authors suggest PAP could also intervene on neuropathological dimensions of ALS, based on neuroprotective properties of psychedelics and robust improvements seen in other populations. They call for future preclinical trials in ALS models and rigorous clinical trials, given the lack of effective treatments for both disease progression and psychological distress.
Neuropharmacology
July 1, 2025
Brennan M. Carrithers, Daniel E. Roberts, Brandon M Weiss et al.
4 citations
Psychedelic therapy may hold potential for treating personality disorders by promoting adaptive changes in personality, though rigorous research is lacking. This review first examines research on psychedelics in individuals with personality disorders using the DSM-5-TR categorical model, then applies the dimensional DSM-AMPD framework to explore how psychedelics might affect self-functioning, interpersonal functioning, and pathological personality traits. The authors discuss clinical relevance, safety considerations, gaps, and recommendations for treating these complex populations.
Journal of Clinical Medicine
February 20, 2025
Shakila Meshkat, Taha Malik, Jennifer Swainson et al.
3 citations
A systematic review examined whether psychedelic therapies can rapidly reduce suicide risk. Four randomized controlled trials reported significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (one study), with effect sizes (Cohen's d) ranging from 0.52 to 1.25 and no safety issues. Five additional randomized trials also showed reductions. Among 24 non-randomized and cross-sectional studies, results were mixed: psilocybin reduced suicidal ideation (odds ratios 0.40–0.75), MDMA-assisted therapy for PTSD showed a pooled effect of d = 0.61, while LSD was associated with increased odds of suicidality (odds ratios 1.15–2.08). DMT studies showed no significant effects. The evidence remains inconclusive, underscoring the need for further trials.
Research Square
October 15, 2024
Alexandra R. Gordon, Brennan M. Carrithers, Broc A. Pagni et al.
3 citations
Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.
Research Square
August 22, 2025
Richard J. Zeifman, George Danias, Gabrielle Agin-Liebes et al.
2 citations
Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder.
The Journal of Clinical Psychiatry
May 9, 2022
Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al.
2 citations
correction
In a meta-analysis of patient-level data on psychedelics and suicidality, two serious adverse events occurred that the original study authors deemed unrelated to the drug. One participant in a very low-dose psilocybin condition (1 mg/70 kg) completed suicide 11 days after administration, having reported boredom and left the session early. Another participant attempted suicide about two months after an active psilocybin dose (21–25.2 mg/70 kg), following a partner's sudden death and subsequent methamphetamine and crack cocaine use, with a brief psychotic episode. These events highlight the need for close monitoring of all participants during and after psychedelic therapy trials.
June 10, 2025
Gabrielle Agin-Liebes, Petros Petridis, Richard J. Zeifman et al.
1 citation
preprint
In a trial where adults with alcohol use disorder received either psilocybin or an active placebo alongside psychotherapy, psilocybin-assisted therapy robustly increased compassionate self-responding and decreased uncompassionate self-responding, with the largest effects on reducing self-judgment, isolation, and over-identification. Across all participants, small but significant correlations linked improvements in self-compassion to reduced drinking. However, in the psilocybin group alone, no significant association emerged between self-compassion gains and drinking reductions, while the control group showed moderate associations. These between-group differences were not statistically significant. Self-compassion appears clinically relevant for alcohol use disorder treatment but may not mediate outcomes when psilocybin is part of therapy.
June 17, 2024
Richard J. Zeifman
1 citation
Psilocybin therapy may improve mental health by reducing experiential avoidance—the tendency to suppress or avoid distressing thoughts and feelings. In a quasi-experimental study with 28 healthy individuals, a high dose (25 mg) of psilocybin led to significant reductions in experiential avoidance at 2 and 4 weeks, sustained at 3 months but not at 6 months, while a very low dose (1 mg) did not. These reductions predicted improvements in well-being and decreases in depressed and anxious mood. In a randomized controlled trial with 59 people with major depressive disorder, psilocybin therapy reduced experiential avoidance more than the antidepressant escitalopram, and these reductions indirectly improved well-being, depression severity, suicidal ideation, and trait anxiety. The findings suggest experiential avoidance is a key mechanism in psilocybin therapy's effects.
Psychedelic Medicine
June 16, 2026
Max Wolff, Samuli Kangaslampi, Richard J. Zeifman et al.
Therapeutic alliance likely plays a meaningful role in shaping both the psychedelic experience and clinical outcomes, contrary to a recent analysis that concluded it did not. This commentary argues that the reported results actually support a meaningful role for alliance when contextualized properly, and that methodological decisions obscured relevant effects. Unexplained deviations from the study protocol also warrant scrutiny. The findings underscore the importance of accurately characterizing psychological and contextual factors in psychedelic treatment research and call for more transparent analyses of psychotherapeutic processes.
May 13, 2026
Robin Carhart-Harris, Richard J. Zeifman, Lorenzo Pasquini et al.
preprint
The paper argues that the term 'plasticity' in neuroscience refers to induced changes in brain function or structure, which differs from the dictionary definition of plasticity as the ability to be shaped or molded. Many biomarkers of neuroplasticity actually index processes that bias phenotypic canalization, the opposite of phenotypic plasticity, creating a paradox. The authors question extrapolating from these biomarkers to improved mental health, as the relationship is context dependent. They propose a new construct, 'mediational and recalibrative plasticity' (MR-P), which aligns with plasticity proper and can describe and predict phenotypic changes relevant to mental health.
Journal of Humanistic Psychology
April 28, 2026
Austin J. Mallard, Matthew Broussard, Richard J. Zeifman et al.
People who have used psychedelics, either currently or in the past, report higher levels of compassionate love, self-compassion, and life satisfaction compared to those who have never used psychedelics. Current users also show greater self-compassion and life satisfaction than past users. Lifetime mystical-type experiences are positively linked to these aspects of positive psychological functioning across all groups, not just among psychedelic users. The findings, based on a cross-sectional survey of 984 people, suggest that psychedelic use and mystical experiences may support well-being, but the study is limited by self-reporting, its cross-sectional design, and a homogenous sample.
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.
European Psychiatry
January 1, 2026
Shakila Meshkat, Qiaowei Lin, Rachel Sousa-Ho et al.
Control groups in psychedelic-assisted psychotherapy trials show substantial symptom improvement, likely due to non-specific factors such as expectancy and concurrent psychotherapy. A meta-analysis of 14 randomized controlled trials (643 participants) found that treatment groups had greater symptom reductions than control groups for depressive symptoms, PTSD symptoms, and anxiety symptoms. For PTSD, inactive placebo groups showed larger within-group improvements. The findings underscore the need for robust control conditions and careful interpretation of treatment effects in psychedelic research.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.