Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboCompleted

Frontline Clinician Psilocybin Study

Double-blind, randomized, parallel-group Phase III study (n=30) comparing single 25 mg oral psilocybin + psychotherapy vs 250 mg niacin active placebo with pre- and post-dose psychotherapy for depression and burnout in frontline healthcare clinicians.

Target Enrollment
30 participants
Study Type
Phase III interventional
Design
Randomized, triple Blind

Detailed Description

This single-site, double-blind randomized controlled trial tests whether a single 25 mg oral dose of psilocybin administered with structured pre- and post-dose psychotherapy reduces depressive symptoms and burnout in physicians and nurses exposed to frontline COVID-19 clinical work.

Participants are randomised 1:1 to receive psilocybin 25 mg or an active placebo (niacin 250 mg) with outcomes assessed at 1 day, 1 week and the primary endpoint at 4 weeks post-dose; placebo participants may receive open-label psilocybin after primary outcome assessment.

Primary outcome is change in clinician-administered MADRS score at 4 weeks; secondary measures include burnout, PTSD-related symptoms and safety/tolerability assessments.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Psilocybin

experimental

Psychedelic-assisted psychotherapy (PAP) + single 25 mg oral psilocybin dose.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Usona Institute psilocybin, single 25 mg session with pre- and post-dose psychotherapy.

Niacin (active placebo)

active comparator

PAP + 250 mg niacin active placebo; participants unblinded after primary outcome and placebo group offered open-label psilocybin.

Interventions

  • Placebo250 mg
    via Oral• single dose• 1 doses total

    Niacin 250 mg active placebo

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. 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
  • 2. Have a Montgomery-Asberg Depression Rating Scale (MADRS) clinician-administered depression score >21, indicating moderately severe symptoms.
  • 3. Have had persistent symptoms despite at least one medication and/or therapy trial of standard care treatment for depression.
  • 4. 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.
  • 5. 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.
  • 6. Must be driven home after the medication dosing session by a driver (which could be a friend, family, rideshare or taxi).
  • 7. 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.
  • 8. Has been off selective serotonin inhibitors (SSRIs) for at least five half-lives of the drug plus 2 weeks.
  • 9. 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
  • 10. 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.
  • 11. If able to bear children, must have a negative pregnancy test at study entry.
  • 12. 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

  • Exclusion Criteria:
  • 1. Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder.
  • 2. Suicidal ideation with a Columbia Suicide Severity Rating Scale (C-SSRS) > 3
  • 3. Current substance abuse disorder (except in the case of mild alcohol use )
  • 4. Neuroleptic and SSRI medications that cannot be tapered and discontinued in conjunction with the participant's prescribing physician.
  • 5. Unstable neurological or medical condition; history of seizure, chronic/severe headaches.
  • 6. Positive urine pregnancy test at the time of screening
  • 7. Any unstable medical condition that my render study procedures unsafe.
  • 8. Any use of psychedelic drugs within the prior 12 months.
  • 9. Use of tramadol, due to the potential for serotonin syndrome with concomitant use of psilocybin.

Study Details

Locations

University of Washington — Seattle, Washington, United States

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