Frontline Clinician Psilocybin Study

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.

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.