Date of Award

2024

Document Type

Dissertation

Degree Name

Doctor of Medical Science (DMSc)

Department

Department of Physician Assistant Medicine

First Advisor

Jason Brumitt

Abstract

Psilocybe cubensis are a group of mushrooms containing psilocybin with a history of consumption dating back to ancient civilization. Researchers believe the ritual use of psilocybin dates back 3,000 years amongst the indigenous people of Mexico and Central America.1 Psilocybin is responsible for the effects associated with the consumption of “Magic Mushrooms”. These effects include hallucinations, delusions, and feelings of derealization. 2 In 1973, the United States federal government classified psilocybin as a Schedule I substance under the Controlled Substance Act, and today the DEA continues to identify the chemical as “high potential for abuse” with “no currently accepted medical use in treatment in the United States”. 3,4 Current legislation, along with a perceived stigma surrounding psilocybin, has restricted researchers’ ability to investigate the therapeutic potential of this compound. However, in recent years there has been increased funding and research related to the therapeutic potential of psilocybin and other psychedelics, highlighted by the creation of the Center for Psychedelic Consciousness Research at John Hopkins in 2019.5

Since the start of the COVID-19 pandemic, the incidence of depression has risen by 25% globally, affecting approximately 175 million individuals, the majority dealing with Major Depressive Disorder (MDD).6 The first-line therapy for patients with MDD include the selective serotonin reuptake inhibitors (SSRI) escitalopram and sertraline. In the event a patient fails treatment through two pharmacological interventions, their depression disorder is considered Treatment-Resistant Depression (TRD).6 Although difficult to know the true number of individuals with TRD, it is estimated that about 30% of the population with MDD fit the description of TRD.7 Current approved treatment for TRD include intranasal esketamine (Spravato), second generation antipsychotics, and olanzapine-fluoxetine. 7

Alternative therapeutic interventions are necessary for the treatment of patients with TRD. Psilocybin may provide potential therapeutic benefits for MDD/TRD. The purpose of this scoping review is to examine the therapeutic benefits, safety, and mechanism of psilocybin in MDD/TRD.

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