🏛️ Verified NIH Record • Updated 2026-08-06

Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression (NCT06506019)

Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression: An Emotional-Processing fMRI Pilot Study

🔵 Active, Not Recruiting Phase1 💊 Investigational Drug / Biologic Sponsor: University Health Network, Toronto

🩺 Plain-English Summary (8th-Grade Level)

This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory, monitoring, and integration psychotherapy sessions (psilocybin-assisted psychotherapy, or PAP). Using fMRI (functional magnetic resonance imaging), the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD. The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose (25 mg) of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder, with 2 or more failed treatment trials (i.e., treatment resistant bipolar depression \[TRBD\]). Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task (determined by fMRI one day after the psilocybin dose) and antidepressant effects (determined by changes in the Montgomery-Åsberg Depression Rating Scale \[MADRS\] scores over time, during the one-week period post-psilocybin dose). This is a single-arm, open-label clinical trial wherein all participants will receive the same study intervention. Hypothesis: Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD.

Who can join: To join this study, participants generally need to meet the listed inclusion criteria (13 items) and avoid the listed exclusions (21 items).

Location: Toronto Western Hospital - University Health Network — Toronto, Ontario

Age range: 18 Years to 65 Years

🧪 Interventions in This Study

📋 "Do I Qualify?" — 1-Minute Self Screener

Instant Checklist

Check every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).

Usually NOT eligible if any of the following apply:

  • Exclusion Criteria:
  • Pregnant as assessed by a urine pregnancy test at Screening (Visit 1) or individual's that intend to become pregnant during the study or are breastfeeding;
  • Treatment with another investigational drug or other intervention within 30 days of Screening (Visit 1);
  • Current symptoms of mania, hypomania or mixed features, as determined by the Young Mania Rating Scale (YMRS) score greater than 12;
  • History of mania or hypomania in the past 6 months as determined by psychiatric history;
  • Have a DSM-5 diagnosis of substance use disorder (excluding use of tobacco) within the preceding 12 months;
  • Have active suicidal ideation as determined by the C-SSRS and/or clinical interview Significant suicide risk is defined by suicidal ideation as endorsed by items 4 or 5 of the C-SSRS, OR active suicidality requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months;
  • Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; psychotic disorder (including but not limited to during previous mood episodes or substance-induced psychosis), bipolar I disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history, the MINI clinical interview, and the International Personality Disorder Examination (IPDE) administered at V1;
  • Have contraindications to fMRI as determined by the MRI questionnaire;
  • Have a history of seizures;
  • Are taking anticonvulsants (with the exception of lamotrigine) or benzodiazepines (lorazepam up to 2mg/day is acceptable);
  • History of Steven-Johnson Syndrome (SJS) or suspected SJS as determined by medical history;

🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.

📍 All Participating Trial Locations (1 Sites)

  • Toronto Western Hospital - University Health Network — Toronto, Ontario

💰 Cost, Insurance & Patient Rights

  • 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
  • Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
  • Voluntary Participation: You may withdraw at any time without affecting your standard medical care.
  • 💵 Compensation indicated: This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by pre...

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💡 How to Participate

  1. Check the checklist above to see if you may qualify.
  2. Review the official NIH record below to find the coordinating site.
  3. Ask about the visit schedule, what is covered at no cost, and any travel support.
  4. Confirm with your own doctor before making a decision.
🏛️ View Official NIH Record ↗