Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression

ConditionBipolar Depression

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-65

SponsorUniversity Health Network, Toronto

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Single group

Treatments tested in this trial

Psilocybin
Drug
25 mg psilocybin
Functional MRI
Device
The fMRI involving resting state measures and a facial affect task will be conducted one-day and one-month after the dosing session.

Treatment groups

30 Participants

are divided into 1 treatment group

Group A: Single Dose PsilocybinExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Correlation of Amygdala Activity on fMRI with MADRS Score

Correlation between changes in the right amygdala signal activity on fMRI during negative emotional stimuli in the facial affect task before and after psilocybin dosing will be evaluated in relation to change in MADRS score.

Time frame

Baseline to 1 and 4 weeks post psilocybin dosing

Change in Depression Symptoms

Depression symptoms will be evaluated using change in Montgomery-Åsberg Depression Rating Scale (MADRS) score, a clinician-administered depression severity rating scale where higher scores indicate greater severity of depression symptoms on a scale of 0-60.

Time frame

Baseline to 4 weeks post psilocybin dosing

Clinical Global Impressions Scale (CGI)

Clinician judgement of illness severity and improvement on a seven-point Likert scale, ranging from "Normal, not at all depressed" to "Among the most extremely depressed patients" and "Very much improved" to "Very much worse". The CGI is evaluated on a scale from 0-30.

Time frame

Baseline to 1 week post psilocybin dosing

Study Recruitment and Retention Rates

Evaluating study feasibility based on recruitment and retention rates

Time frame

Washout period to 4 week post psilocybin dosing

Secondary outcomes

Self-Reported Depression Symptoms

Self-assessment of depression symptoms using the Quick Inventory for Depressive Symptomatology, Self-Report (QIDS-SR) where higher scores indicate greater severity on a scale of 0-42.

Time frame

Baseline to 4 weeks post psilocybin dosing

Self-Reported Anxiety Symptoms

Self-assessment of anxiety symptoms using the Generalized Anxiety Disorder 7-Item (GAD-7) where higher scores indicate greater severity on a scale from 0-21.

Time frame

Baseline to 4 weeks post psilocybin dosing

Subjective Functioning

Self-assessment of subjective function as measured by the Sheehan Disability Scale (SDS) where higher scores indicate greater severity of disability symptoms on a scale from 0-30.

Time frame

Baseline to 4 weeks post psilocybin dosing

Self-Reported Quality of Life

Self-assessment of quality of life measured by the World Health Organization-5, Well-Being Index (WHO-5) where higher scores indicate a better quality of life score on a scale from 0-25.

Time frame

Baseline to 4 weeks post psilocybin dosing

Other outcomes

Self-Reported Mystical Experience

Self-assessment of the degree of mystical experiences following psilocybin administration using the Mystical Experience Questionnaire (MEQ). The MEQ assesses 4 empirically derived factors: mystical experiences, positive mood, transcendence of time and space and ineffability (e.g. inability to adequately describe experience in words). Responses are rated on a 6-point Likert scale ranging from 0 (none, not at all), through to 5 (extreme, more than ever before in my life).

Time frame

Immediately post psilocybin dosing

Self-Reported Anhedonia Symptoms and Reward Thinking

Self-assessment of anhedonia symptoms across four domains: hobbies/past-times, food/drinks, social activities, and sensory experiences as measured by the Dimensional Anhedonia Rating Scale (DARS). Participants are asked to provide at least two of their own examples of what they find rewarding under each domain. The DARS is evaluated on a scale from 0-51 where lower scores indicate greater anhedonic symptoms.

Time frame

Baseline to 4 weeks post psilocybin dosing

Psychomotor Speed, Visual search, and Attention

The Trail Making Test B (TMT-B) requires participants to connect numbered circles with a pencil as quickly as possible in an alternating alphanumeric sequence respectively. Shorter time to complete these tests and fewer errors denotes higher performance.

Time frame

Baseline to 4 weeks post psilocybin dosing

Psychomotor Performance

The Digit Symbol Substitution Test (DSST) is a pencil and paper test of psychomotor performance. Participants will be key grid of numbers and matching symbols and are asked to fill as many empty boxes as possible with the symbol matching each number. The score is the number of correct number-symbol matches achieved in 90 seconds.

Time frame

Baseline to 4 weeks post psilocybin dosing

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Health Network, Toronto

Lead sponsor

Centre for Addiction and Mental Health

Collaborator

Source ClinicalTrials.gov

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