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Divergent Effects of Psilocybin for 2 Patients Participating in a Psilocybin-assisted Cognitive Behavioral Therapy Trial for Major Depressive Disorder.

Marc J. Weintraub, David J. Miklowitz, Jessica K Jeffrey

Journal of Psychiatric Practice May 1, 2025 DOI: 10.1097/pra.0000000000000853 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Case study Case report Peer reviewed
Sample size 2
Population Patients with major depressive disorder in a clinical trial
Interventions Psilocybin Cognitive behavioral therapy
Dose 10 and 25 mg
Duration 7-month study
Topics Psilocybin Depression
Keywords Depressive disorders Drug/psychotherapy combination Depression treatment Psilocybin therapy Psychedelic medicine Cbt Treatment outcomes
Key findings Psilocybin-assisted cognitive behavioral therapy produced immediate and sustained antidepressant effects in one patient but minimal to no effects in another, highlighting divergent individual responses.

Abstract

We present divergent experiences of 2 patients who participated in a clinical trial of psilocybin-assisted cognitive behavioral therapy for major depressive disorder. Both patients participated in an open trial involving 2 drug administration sessions separated by one month (10 and 25 mg, respectively) along with 12 sessions of cognitive behavioral therapy. The first of the 2 patients had powerful and beneficial experiences on psilocybin that led to immediate and sustained antidepressant effects over the 7-month study. The second participant reported significant challenges with psilocybin and minimal to no antidepressant effects following the drug administration. We present the clinicians' experiences who treated both patients. Finally, we theorize and discuss areas of future research to elucidate how psilocybin can yield the greatest psychiatric benefit, the conditions within the patient that can lead to (or inhibit) psychiatric benefit, and the psychosocial environment that can best facilitate psilocybin therapy.

Comparable studies

Other case reports and case series on psilocybin for depression, most cited first.

Study Year Design Participants
Underground small-group therapy of treatment-resistant depression and complex post-traumatic stress disorder (C-PTSD) with psilocybin—A retrospective case study A woman in her early forties with early complex trauma and treatment-resistant depression 2023 Case report n = 1
Self-treatment of depression and complex post-traumatic stress disorder with psilocybin and LSD—A retrospective case study Young man with early-onset complex trauma, anxiety, and depression 2023 Case study n = 1
Psilocybin-assisted psychotherapy for Parkinson's disease without depression: A case-report. Non-depressed 43-year-old female with a 2-year history of Parkinson's disease 2025 Case study n = 1
Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report Adult patient with difficult-to-treat depression 2024 Case report n = 1
Self-treatment of parental neglect-induced mixed anxiety and depressive disorder with psilocybin – A retrospective case study Young woman in her mid-twenties with a history of depression since childhood 2023 Case study n = 1

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