Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression (NCT06506019) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression
Canada30 participantsStarted 2024-10-09
Plain-language summary
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 participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Adults 18 to 65 years old.
. Must be deemed to have capacity to provide informed consent;
. Must sign and date the informed consent form;
. Stated willingness to comply with all study procedures;
. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
. Primary DSM-5 diagnosis of Bipolar II Disorder (BD-II) currently experiencing a Major Depressive Episode (MDE) without psychotic features as diagnosed by a mood disorder specialist and confirmed using the Mini-International Neuropsychiatric Interview (MINI);
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Correlation of Amygdala Activity on fMRI with MADRS Score
Timeframe: Baseline to 1 and 4 weeks post psilocybin dosing
2
Change in Depression Symptoms
Timeframe: Baseline to 4 weeks post psilocybin dosing
3
Clinical Global Impressions Scale (CGI)
Timeframe: Baseline to 1 week post psilocybin dosing
4
Study Recruitment and Retention Rates
Timeframe: Washout period to 4 week post psilocybin dosing
. Current MDE must be moderate to severe, as determined by the Hamilton Depression Rating Scale (HDRS-17) score greater than 20 with inadequate response to two or more adequate evidence-based treatment trials for bipolar depression, as per the 2018 CANMAT Bipolar Disorder Guidelines. Treatment trials are specific to current MDE rather than lifelong trials;
. Ability to take oral medication;
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;