The Effects of Psilocybin on Treatment Resistant Depression (TRD)


Psilocybin is a tryptamine alkaloid found in several species of Psilocybin mushrooms. Its potential antidepressant efficacy was suggested by preliminary studies in patients with major depressive disorder (MDD) in the context of life-threatening cancer. Amelioration of symptomatic depression in pilot studies of MDD, including a trial compared to escitalopram, and in treatment resistant depression (TRD) suggest therapeutic potential for this agent (1). Psilocybin therapy is now in clinical development for treatment-resistant depression after these early promising indications of efficacy in depressive states. Data from studies in treatment resistant depression will be reviewed including results from the largest randomized controlled trial of psilocybin to date.

In recent studies, at the 3-week primary endpoint psilocybin administered in a single session as monotherapy at a 25 mg dose with psychological support showed a significantly greater improvement in depression rating total scores compared to a 1 mg dose in mostly psychedelic-naïve TRD participants but was associated with some adverse events (2). Longer and larger trials, including comparison to existing treatments, are required to determine the efficacy and safety of psilocybin for TRD. Pilot studies are underway in bipolar depression and commonalities with other novel treatments, particularly ketamine, will be discussed.

Professor Allan Young is Chair of Mood Disorders and Director of the Centre for Affective Disorders in the Department of Psychological Medicine in the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, where he is also Head of School for Academic Psychiatry. The School of Academic Psychiatry is second in the world rankings for Psychiatry ( He is the clinical academic lead in the Psychological Medicine and Integrated Care Clinical Academic Group in the South London and Maudsley NHS Trust, where he is also Consultant Psychiatrist and Head of the Affective Disorders Service.

Professor Young’s research interests focus on the cause and treatments for severe psychiatric illnesses, particularly mood disorders. He has received research grants from several funding agencies and has over 700 peer-reviewed publications, including several books about psychopharmacology and affective disorders. He is editor of the Journal of Psychopharmacology and deputy editor of the British Journal of Psychiatry (Open). His H-index is 126 with over 88000 citations of his papers. Recent publications have been in the New England Journal of Medicine, JAMA Psychiatry, World Psychiatry and Lancet Psychiatry. Professor Young is a Clarivate Highly Cited Researcher: this highly anticipated annual list identifies researchers who demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index. Professor Young has current grant funding exceeding £30 million (

He is past President of the International Society for Affective Disorders, past President of the British Association of Psychopharmacology and the Inaugural Chair of the Special Committee for Psychopharmacology of the Royal College of Psychiatrists. He is also a trustee of the patient and family charity Bipolar UK, and of the Drug Safety Research Unit (DSRU), which is internationally respected for its work in Pharmacovigilance, Pharmacoepidemiology, Risk Management and Training Services for over 30 years.



1. Rucker JJH, Jelen LA, Flynn S, et al.: Psychedelics in the treatment of unipolar mood disorders: A systematic review. J Psychopharmacol 2016; 30:1220–1229

2. Goodwin et al, NEJM, 2022 Nov 3;387(18):1637-1648. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. doi: 10.1056/NEJMoa2206443.

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