Skip to content

David J Hellerstein

Department of Psychiatry, Washington University School of Medicine, St. Louis (Bender, Siegel, Ercal, Lenze); Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore (Nayak); Langone Center for Psychedelic Medicine, Department of Psychiatry, Grossman School of Medicine, New York University, New York City (Siegel); Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, and New York State Psychiatric Institute, New York City (Hellerstein).

9 papers in the library · 1,403 citations · publishing 2022-2026

Papers

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

The New England journal of medicine November 3, 2022 Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. 1,095 citations

A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life

Journal of Affective Disorders February 3, 2023 Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. 168 citations

Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.

Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder.

Journal of psychiatric research May 1, 2023 Franklin R Schneier, Jamie Feusner, Michael G Wheaton et al. 79 citations

A single 25 mg oral dose of psilocybin, given with psychological support, significantly reduced body dysmorphic disorder (BDD) symptoms in 12 adults whose condition had not responded to at least one prior serotonin reuptake inhibitor. Over 12 weeks of follow-up, scores on a standard BDD severity scale decreased substantially, with a large effect size and improvements evident from week 1 and sustained through week 12. Seven of 12 participants (58%) showed a 30% or greater reduction in symptoms at week 12. No serious adverse events occurred. These preliminary findings suggest psilocybin may be a promising treatment for BDD, warranting further controlled trials.

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Journal of affective disorders March 1, 2025 Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. 35 citations

In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.

Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder.

The Journal of clinical psychiatry March 3, 2025 Guy M Goodwin, Ania Nowakowska, Merve Atli et al. 14 citations

A single 25 mg dose of the synthetic psilocybin formulation COMP360 showed a longer time before depressive events recurred over 52 weeks compared with 1 mg and 10 mg doses in people with treatment-resistant depression. In the full group of 233 participants, the median time to a depressive event was 92 days for the 25 mg group, 83 days for the 10 mg group, and 62 days for the 1 mg group. Most participants had a depressive event by 12 weeks. Adverse events were rare; one case of mild suicidal ideation in the 1 mg group was considered possibly related to the drug. Larger long-term studies are needed to confirm these results.

The Role of Touch in Psychedelic Therapy: Perspectives From a Survey of Practitioners in Research Settings.

American journal of psychotherapy May 6, 2025 David A Bender, Sandeep M Nayak, Joshua S Siegel et al. 7 citations

Practitioners of psychedelic therapy largely view physical touch as an important component of treatment, but they also emphasize strict professional boundaries and the necessity of patient consent. In a survey of 40 practitioners who had overseen an average of 41.4 psychedelic sessions, 70% agreed that therapeutic touch is crucial. However, most deemed specific forms of touch inappropriate: 63% considered bodywork inappropriate, and 98% considered full-body contact inappropriate. Free-response analysis showed 96% supported touching the patient's hand and 58% supported touching the shoulder. Unprompted, 63% of respondents stressed the importance of consent. These views may inform future practice.

Psychological Support Approaches in Psychedelic Therapy: Results From a Survey of Psychedelic Practitioners.

The Journal of clinical psychiatry February 5, 2025 David A Bender, Sandeep M Nayak, Joshua S Siegel et al. 3 citations

Practitioners who oversee psychedelic therapy sessions slightly prefer an 'emotive' approach—one that emphasizes human and spiritual elements—over a 'neuromodulatory' approach that focuses on biological drug effects. A survey of 40 qualified respondents from at least 4 countries, 11 U.S. states, and 16 institutions found no consensus on many psychological support strategies. Four key themes emerged: the importance of trust, the role of spirituality, creating an emotional setting, and conceptualizing negative experiences. Practitioners trained at the Multidisciplinary Association for Psychedelic Studies or the California Institute of Integral Studies showed a significantly stronger emotive preference than those trained elsewhere.

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.

Journal of affective disorders August 1, 2026 Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. 2 citations

In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.

Provider perspectives on challenges in treatment during psychedelic therapy.

Psychopharmacology October 27, 2025 David A Bender, Sandeep M Nayak, Joshua S Siegel et al.

Providers administering psychedelic drugs in clinical trials report a range of challenges, including intense dysphoria during sessions (42% of respondents), disappointment with the intervention (25%), and re-engaging with traumatic experiences (17%). An anonymous survey of 40 qualified respondents who oversaw 1656 psychedelic sessions identified 11 distinct themes of challenges. 70% of respondents felt that individuals with PTSD or prior trauma need additional psychological support, and they recommended an average of 9.8 hours of total psychological support for first-time recipients with serious mental illness. These findings highlight the need to incorporate potential adverse experiences into psychological support protocols for clinical trials and future guidelines.