Category: Parkinson’s Disease: Clinical Trials
Objective: To investigate the safety, tolerability, feasibility, and preliminary efficacy of moderate and high dose psilocybin treatment with psychotherapeutic support for comorbid Parkinson’s disease (PD) and mood dysfunction
Background: Depression and anxiety are common in PD, often treatment-resistant, and linked to reduced quality of life as well as accelerated physical and cognitive decline [1,2]. Early evidence suggests that the serotonergic psychedelic psilocybin may be a promising novel intervention for treatment-resistant depression  and mood dysfunction in people with terminal cancer [4,5]. However, no prior psilocybin trials have enrolled participants with PD or any other neurodegenerative illness.
Method: This is an open-label single-arm pilot study enrolling people (N=15) ages 40 to 75 with idiopathic PD (Hoehn and Yahr stages 1-3) who also meet Diagnostic and Statistical Manual, 5th Edition criteria for a depressive and/or anxious disorder. Participants receive a 10 mg oral administration of psilocybin followed approximately 2 weeks later by a 25 mg administration, each in a physician-monitored setting with psychological support. Participants complete psychotherapy sessions before and after each drug administration session. Primary outcomes are safety and tolerability measured by the incidence, severity, and treatment-relatedness of adverse events (AEs) elicited through assessments of the following: vital signs, acute subjective drug effects, motor and non-motor symptoms, psychotic symptoms, suicidality, cognitive performance, and care partner distress. The secondary outcome is feasibility measured by recruitment and retention rates as well as treatment satisfaction. Exploratory efficacy outcomes are severity of depression and anxiety measured by clinical assessments as well as functional impairment and quality of life measured by participant report. As this is a pilot study, no formal sample size calculation was performed.
Results: This study is ongoing and planned to finish in June 2023. To date, 13 people have enrolled, 12 have completed the 10 mg session and 12 have completed the 25 mg session. No participants have declined the second drug administration session, and treatment has been well-tolerated with no serious AEs thus far.
Conclusion: This study will provide the first data on the potential of psilocybin therapy for people with PD and mood dysfunction.
References:  Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG. A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1992;55(5):377-382. doi:10.1136/jnnp.55.5.377
 Weintraub D, Mamikonyan E. The Neuropsychiatry of Parkinson Disease: A Perfect Storm. Am J Geriatr Psychiatry. 2019;27(9):998-1018. doi:10.1016/j.jagp.2019.03.002
 Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016;3(7):619-627. doi:10.1016/S2215-0366(16)30065-7
 Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol Oxf Engl. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
 Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol (Oxf). 2016;30(12):1165-1180. doi:10.1177/0269881116675512
To cite this abstract in AMA style:E. Bradley, K. Sakai, G. Fernandes, C. Ludwig, M. Bock, J. Ostrem, C. Tanner, A. O'Donovan, P. Finley, Z. Busby, A. Mckernan, R. Zuzuarregui, A. Penn, A. Wang, A. Theberge, R. Rosen, J. Woolley. Psilocybin therapy for depression and anxiety associated with Parkinson’s disease: a pilot study (NCT04932434) [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/psilocybin-therapy-for-depression-and-anxiety-associated-with-parkinsons-disease-a-pilot-study-nct04932434/. Accessed September 23, 2023.
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