Psychopharmacology
February 1, 2021
Richard J Zeifman, Nikhita Singhal, Rafael G Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
Scientific reports
April 17, 2024
Jordan Sloshower, Richard J Zeifman, Jeffrey Guss et al.
56 citations
Psilocybin-assisted therapy improves psychological flexibility, mindfulness, and values-congruent living in people with moderate to severe major depressive disorder, and these improvements are strongly linked to reductions in depression severity. In an exploratory placebo-controlled study, participants received placebo then psilocybin (0.3 mg/kg) four weeks later, with dosing sessions embedded in Acceptance and Commitment Therapy. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved after psilocybin and were maintained through week 16. The findings suggest that increasing psychological flexibility may be a key mechanism underlying psilocybin's therapeutic effects.
Journal of affective disorders
August 1, 2023
Richard J Zeifman, Anne C Wagner, Candice M Monson et al.
56 citations
In a double-blind randomized controlled trial comparing psilocybin therapy (two 25 mg sessions plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among 59 individuals with major depressive disorder, reductions in experiential avoidance mediated improvements in well-being, depression severity, suicidal ideation, and trait anxiety only in the psilocybin group. Exploratory analyses indicated that these improvements (except for suicidal ideation) occurred serially through increased connectedness. Experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance. The findings support reduced experiential avoidance as a mechanism underlying psilocybin therapy's positive outcomes.
Scientific Reports
February 7, 2024
Christopher Timmermann, Richard J Zeifman, David Erritzoe et al.
37 citations
Intravenous DMT, a fast-acting psychedelic, improved depression scores in healthy volunteers one to two weeks after administration. In a placebo-controlled comparison (13 participants) and a prospective dataset (17 participants), depression severity decreased significantly. Reductions in trait neuroticism appeared only in the placebo-controlled sample. Changes in depression and anxiety correlated with the intensity of acute peak experiences, suggesting that DMT may reduce depressive symptoms by inducing such experiences. The short half-life and flexible dosing of intravenous DMT make it a practical candidate for psychedelic medicine, though further research in clinical samples is needed.
European journal of psychotraumatology
January 1, 2024
Richard J Zeifman, Hannes Kettner, Stephen Ross et al.
34 citations
Therapeutic alliance—the quality of the relationship between therapist and client—predicts improvement in PTSD symptoms after MDMA-assisted psychotherapy. Among 22 adults with chronic PTSD who received MDMA during a clinical trial, stronger therapeutic alliance measured at sessions 4 and 9 (but not before the third session) was associated with lower clinician-assessed PTSD severity after treatment, even after accounting for initial symptom severity. Self-reported PTSD severity was also predicted by alliance at baseline, session 4, and session 9, though the baseline finding did not survive correction for multiple comparisons. These results provide initial evidence that common psychotherapeutic factors like alliance contribute to outcomes in MDMA-assisted therapy.
Scientific reports
January 29, 2025
Richard J Zeifman, Meg J Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
European journal of psychotraumatology
December 1, 2025
Gabrielle Agin-Liebes, Richard J Zeifman, Jennifer M Mitchell
11 citations
MDMA-assisted therapy (MDMA-AT) for severe posttraumatic stress disorder (PTSD) improves self-compassion, which may explain its therapeutic benefits. In a double-blind trial with 82 adults, MDMA-AT significantly increased compassionate self-responding (self-kindness, common humanity, mindfulness) and decreased uncompassionate self-responding (self-judgment, isolation, over-identification) compared to placebo plus therapy, with large effect sizes on most subscales. Changes in self-compassion fully mediated the reduction in PTSD severity and depressive symptoms, but not in alcohol or substance use. Self-compassion appears to be a key psychological mechanism in MDMA-AT, suggesting that targeting it could refine treatments for PTSD with co-occurring depression.
Neuroscience and biobehavioral reviews
June 1, 2025
Shakila Meshkat, Gunjan Malik, Richard J Zeifman et al.
11 citations
Psilocybin-assisted psychotherapy may reduce alcohol consumption and help with smoking cessation, especially for alcohol and tobacco use disorders. In a systematic review of 16 published studies, most focused on alcohol or tobacco use, and over half used psilocybin combined with psychotherapy. Doses ranged from microdosing to 20–40 mg per 70 kg. Alcohol use disorder studies reported fewer heavy drinking days and higher abstinence rates, with brain scans showing normalized activity. Tobacco use disorder studies found high smoking abstinence rates, with mystical experiences predicting long-term success. Findings for other substance use disorders were mixed. The evidence is preliminary; larger clinical trials are needed.
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.