PET-SPIDER: PET Synaptogenesis After Psilocybin In DEpression Recovery

Sponsor

Washington University School of Medicine (Other)

Overall Status

Withdrawn

CT.gov ID

NCT05601648

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Anhedonia	Drug: Psilocybin	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open label treatment study, no placebo.Open label treatment study, no placebo.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

SV2A Marker of Synaptogenesis in a Clinical Trial of Psilocybin for Depression

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin Eligible adults to undergo a single drug session with psilocybin (25mg tablet) plus supportive psychotherapy	Drug: Psilocybin Psilocybin (25mg tablet) plus supportive psychotherapy

Arm

Intervention/Treatment

Experimental: Psilocybin

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

Drug: Psilocybin

Psilocybin (25mg tablet) plus supportive psychotherapy

Outcome Measures

Primary Outcome Measures

Synaptogenesis in hippocampus [7 days after psilocybin]
Change in 11C-UCB-J signal in the hippocampus from baseline to post-treatment PET scans.
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.

Secondary Outcome Measures

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).
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.

Other Outcome Measures

Limbic functional connectivity, measured with resting state functional MRI [7 days after psilocybin]
Resting state functional connectivity magnetic resonance imaging measures fluctuations in blood oxygenation level dependent (BOLD) signal in the brian. Functional connectivity (FC) analysis measures correlation in BOLD signal between brain areas. FC studies of depression have suggested pathological hyperconnectivity between cortical regions involved in mood and emotion (subgenual anterior cingulate, or sgACC), and the sense of self and rumination (default mode network or DMN). Identifying correlates of neurotrophic stimulation with rsfMRI would be of tremendous value. By acquiring concurrent PET + MRI in the same subjects the investigators will directly test the viability limbic FC as a surrogate marker of synaptogenesis (measured by PET).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women between 18 and 65 years of age;
Able to provide informed consent
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
Willingness to comply and be available for all study requirements, including psychological, cognitive, and imaging for the duration of the study
Meeting DSM-5 criteria for major depressive disorder and current depressive episode
Snaith-Hamilton Anhedonia Pleasure Scale (SHAPS) ≥ 6 points
Willing and able to taper and/or discontinue current psychotropic medications

Exclusion Criteria:

Women who are pregnant or who intend to become pregnant or nurse during the study duration.
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);
Use of psychotropic medication that may interact with psilocybin (TCA, MAOi, antipsychotic/neuroleptics, anti-epileptic/mood stabilizer, lithium, SSRI, SNRI, Mirtazapine, Buproprion, Vortioxetine).
Recent use of psychedelics (psilocybin, LSD, ayahuasca, mescaline; past 5 years); or prior severe adverse reactions to psychedelics
Active suicidal ideation or history of a suicide attempt.
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);
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);
Presence of contraindications to PET or MRI scanning (renal disease, implantable devices, bone hardware, some IUDs);
Body mass index >30 (due to MRI confounds).