Frontline Clinician Psilocybin Study

Study Overview
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Brief Summary
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This study aims to investigate the effects of a single dose of psilocybin, delivered in the contextof pre- and post-dose psychotherapy, on symptoms of depression and burnout suffered by healthcare clinicians as a result of frontline work in the COVID pandemic.

Detailed Description
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Aim 1: To assess short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of depression experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 1.1: Compared to active placebo, PAP will result in short term improvement in symptoms of depression 1 day and 1 week after the psilocybin dose session. Hypothesis 1.2: Compared to active placebo, PAP will result in longer term improvement of symptoms of depression 4 weeks after the medication dosing session. The primary outcome will be a comparison between the psilocybin 25 mg vs control groups of a combination of depression symptoms measured at 4 weeks post medication dose session. 1.1.2. Aim 2: To explore short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of burnout experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 2.1: Compared to active placebo, PAP will result in short term improvement in symptoms of burnout 1 day and 1 week after the psilocybin dose session.

Official Title
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A Randomized, Placebo-controlled Trial of Psychedelic-assisted Psychotherapy With Single Dose Psilocybin for Frontline Clinicians Experiencing COVID-related Symptoms of Depression and Burnout

Conditions
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Burnout, Caregiver, Burnout, Professional, COVID-19, Depression, Post Traumatic Stress Disorder, Moral Injury

Intervention / Treatment
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* Drug: Psilocybin (Usona Institute)
* Drug: Active placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be physicians or nurses with at least 1 month of frontline clinical experience during the COVID pandemic who rate at least 2 of 4 items from the COVID Exposure index as 'more than half the days' during their peak 2 week period of exposure: i. Caring for someone critically ill with COVID-19, or who became critically ill while you were involved; ii. Working longer hours than usual in order to provide assistance or care to individuals with COVID-19; iii. Witnessing or responding to a death related to COVID-19, or losing a patient you had been caring for to COVID-19; iv. Caring for patients who have died without family physically present due to COVID-19 precautions Have a Montgomery-Asberg Depression Rating Scale (MADRS) clinician-administered depression score >21, indicating moderately severe symptoms. Have had persistent symptoms despite at least one medication and/or therapy trial of standard care treatment for depression. English speaking - able to understand the process of consent and the risk and benefits associated with the study, and able to give written informed consent. Must be willing to sign a medical release for the investigators to communicate directly with their therapist and doctors to confirm a medication and/or medical history. This is decided on a case-by-case basis upon the discretion of the PI. Must be driven home after the medication dosing session by a driver (which could be a friend, family, rideshare or taxi). Must provide at least one adult to have continuous contact with the participant, provide participant transportation, monitor changes in the participant's behavior, and notify research staff of behavior changes. Has been off selective serotonin inhibitors (SSRIs) for at least five half-lives of the drug plus 2 weeks. Must avoid taking any psychiatric medications or starting a new psychiatric medication during the study. Should participant's doctor recommend starting a new psychiatric medication, participant will be required to notify the study team and the subject would withdraw from the study Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the Clinical Investigators in the event of a participant becoming suicidal. If able to bear children, must have a negative pregnancy test at study entry. Are willing to commit to preparation sessions, medication dosing sessions, integration sessions, to complete evaluation instruments and commit to be contacted for all necessary telephone contacts. Exclusion Criteria: Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder. Suicidal ideation with a Columbia Suicide Severity Rating Scale (C-SSRS) > 3 Current substance abuse disorder (except in the case of mild alcohol use ) Neuroleptic and SSRI medications that cannot be tapered and discontinued in conjunction with the participant's prescribing physician. Unstable neurological or medical condition; history of seizure, chronic/severe headaches. Positive urine pregnancy test at the time of screening Any unstable medical condition that my render study procedures unsafe. Any use of psychedelic drugs within the prior 12 months. Use of tramadol, due to the potential for serotonin syndrome with concomitant use of psilocybin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study tests a hypothesis that a single session of psilocybin (the 'medication dosing' session) in the context of pre- and post-dose psychotherapy will result in improvement of symptoms of depression and burnout measured 4 weeks post-dose. This study hypothesis will be tested in a single site, double-blind, randomized controlled design involving 30 clinician participants that will compare effects of a single 25mg oral dose of psilocybin to a 250 mg of niacin (active placebo). The primary outcome measurements will be collected 4 weeks after the psilocybin dose, after which the participant group assignment will be unblinded, and participants who received niacin will be offered the opportunity to have a second dose session with a 25 mg dose (with pre- and post-dose psychotherapy).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin arm<br>psychedelic assisted psychotherapy + 25mg psilocybin | Drug: Psilocybin (Usona Institute)<br>* PAP + psilocybin 25 mg<br>* Other names: Psychedelic-assisted psychotherapy (PAP);|
| Active Comparator: Placebo<br>Psychedelic assisted psychotherapy + 250mg niacin | Drug: Active placebo<br>* PAP + niacin 250mg<br>* Other names: PAP with placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale | Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms | 4-weeks post psilocybin-assisted psychotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale | Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms | 1, 8, 12, 24 weeks post-psilocybin-assisted psychotherapy | 
| Stanford Fulfillment Index | Assesses professional burnout in 3 components that are scored separately (professional fulfillment, interpersonal disengagement, work exhaustion) | 1,4,8,12,24 -weeks post psilocybin-assisted psychotherapy | 
| PTSD Checklist for DSM-5 (PCL5) | Assesses symptoms of post-traumatic stress disorder; minimum score 0, max 80; higher scores indicate more severe symptoms of PTSD | 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy | 
| Moral injury symptom scale | Assesses symptoms of moral injury: minimum score 10, max 100; higher score indicates more severe symptoms | 4, 24 weeks post-psilocybin-assisted psychotherapy | 
| Beck Depression Index | Assess self-reported symptoms of depression: minimum score 0, max 63; higher score indicates more severe symptoms of depression | 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psilocybin, psychedelic assisted psychotherapy