PET Synaptogenesis After Psilocybin In DEpression Recovery

Phase 2

Withdrawn

• Conditions: Anhedonia; Major Depressive Disorder
• Interventions: Drug: Psilocybin

• Registration Number: NCT05601648
• Lead Sponsor: Washington University School of Medicine

Brief Summary

Participants with depression will be given a single dose of psilocybin and supportive psychotherapy before, during, and after drug administration. Participants will undergo positron emission tomography (PET) imaging before and one week after psilocybin using a marker of synaptic density. This design allows us to assess the relationship between neurotrophic, and antidepressant effects produced by psilocybin.

Detailed Description

The investigators are studying the neurotrophic effects of psilocybin using 11C-UCB-J, a PET marker for synaptogenesis. Psilocybin is a naturally occurring psychedelic and exerts perceptual effects via 5-HT2A receptor agonism. Psilocybin has gained a great deal of attention as a tool for psychiatric treatment, with clinical trials demonstrating symptom relief after a single dose that is immediate and persists for months. Recognizing the therapeutic potential of psilocybin, the US Food and Drug Administration granted breakthrough therapy status to the Usona Institute for Phase 2 testing of psilocybin in depression. Animal models suggest that psychedelics exert antidepressant effects by producing a rapid and powerful neurotrophic response in the brain.

The investigators will enroll patients with major depressive disorder and anhedonia. Participants will be given a single dose of psilocybin and supportive psychotherapy before, during, and after drug administration. Participants will undergo PET imaging before and one week after drug using 11C-UCB-J, a radiotracer that binds to SV2A - a marker of synaptic density and synaptogenesis. This design allows the investigators to assess the relationship between neurotrophic, and antidepressant effects produced by psilocybin.

Study Timeline

• Study First Submitted: 2022-10-17
• Study First Submitted QC: 2022-10-31
• Study First Posted: 2022-11-01
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-26
• Last Update Posted: 2023-01-30
• Study Start: 2023-07-01
• Primary Completion: 2025-01-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Men and women between 18 and 65 years of age;
2. Able to provide informed consent
3. Women of childbearing age must agree to be on two forms of contraception and men are required to utilize at least one form of contraception
4. Willingness to comply and be available for all study requirements, including psychological, cognitive, and imaging for the duration of the study
5. Meeting DSM-5 criteria for major depressive disorder and current depressive episode
6. Snaith-Hamilton Anhedonia Pleasure Scale (SHAPS) ≥ 6 points
7. Willing and able to taper and/or discontinue current psychotropic medications

Exclusion Criteria

1. Women who are pregnant or who intend to become pregnant or nurse during the study duration.
2. Presence of psychiatric conditions that are contraindications to psilocybin exposure (e.g., personal or first degree relative with history of schizophrenia spectrum or bipolar disorder);
3. Use of psychotropic medication that may interact with psilocybin (TCA, MAOi, antipsychotic/neuroleptics, anti-epileptic/mood stabilizer, lithium, SSRI, SNRI, Mirtazapine, Buproprion, Vortioxetine).
4. Recent use of psychedelics (psilocybin, LSD, ayahuasca, mescaline; past 5 years); or prior severe adverse reactions to psychedelics
5. Active suicidal ideation or history of a suicide attempt.
6. Presence of medical conditions that are contraindications to psilocybin exposure (e.g., neurological conditions or severe hypertension, severe and/or unstable metabolic or cardiovascular conditions);
7. Current medical conditions that are known to increase risk of severe coronavirus infection or deemed by a study physician to put an individual at high risk (i.e., cancer, COPD, obesity, immunosuppression, type 2 diabetes, serious heart conditions, sickle cell disease, asthma);
8. Presence of contraindications to PET or MRI scanning (renal disease, implantable devices, bone hardware, some IUDs);
9. Body mass index >30 (due to MRI confounds).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Psilocybin	Psilocybin	Eligible adults to undergo a single drug session with psilocybin (25mg tablet) plus supportive psychotherapy

Primary Outcome Measures

Name	Time	Method
Synaptogenesis in medial prefrontal cortex	7 days after psilocybin	Change in 11C-UCB-J signal in the medial prefrontal cortex from baseline to post-treatment PET scans.
Synaptogenesis in hippocampus	7 days after psilocybin	Change in 11C-UCB-J signal in the hippocampus from baseline to post-treatment PET scans.

Secondary Outcome Measures

Name	Time	Method
Change in anhedonia symptoms	7 days after psilocybin	Change in Snaith-Hamilton Anhedonia Pleasure Scale (SHAPS) - is a 14 item self-report measure assessing pleasure response/hedonic experience across domains. The SHAPS measures both anticipation and experience of pleasure. A score is obtained by making binary (disagree/strongly disagree =1) and summing the 14 items - range 0-14, greater than 3 is considered abnormal.
Change in major depressive disorder symptoms	7 days after psilocybin	Change in Montgomery-Asberg Depression Rating Scale (MADRS) - score range 0-60 (higher score equals greater severity of depressive symptoms).

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States