Anhedonia, Emotional Blunting
Conditions
Keywords
SSRI, SNR, Depression, Anhedonia, Emotional Blunting, Psilocybin
Brief summary
This study is for adults with major depressive disorder (depression) who are currently taking an SSRI or SNRI antidepressant but continue to experience anhedonia (reduced interest or pleasure) and emotional blunting. The study will test whether a single 25 mg dose of psilocybin, compared with placebo, can improve these symptoms and improve the function of brain circuits involved in reward and motivation. Researchers will measure changes using brain imaging (fMRI) and clinical questionnaires, including the Dimensional Anhedonia Rating Scale (DARS).
Interventions
DRUGPsilocybin
One-time dose of psilocybin 25 mg, oral, in capsule form.
DRUGPlacebo
One-time dose of placebo (25 mg of inert filler), oral, in capsule form.
Sponsors
NYU Langone Health
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 65 years * Able to provide voluntary signed and dated informed consent. * Females of childbearing potential (FOCBP) must agree to practice an effective means of birth control throughout the duration of the trial * Males who have FOCBPs as partners must agree to practice an effective means of birth control throughout the duration of the trial * State willingness to comply and be available for all study requirements, including psychological, cognitive, imaging and procedural evaluations for the duration of the study * Meet DSM-5 criteria for major depressive disorder (MDD) * Screening Dimensional Anhedonia Rating Scale (DARS) total score of \< 28.5 points * Have an identified support person * Agree to refrain from taking all non-prescription medications and supplements (nutritional and herbal) for at least 1 week prior to the IP administration session unless approved by the Investigator.
Exclusion criteria
* Inability to speak and understand English sufficiently to complete informed consent and study procedures. * Inability to provide informed consent. * Women who are pregnant or who intend to become pregnant or nurse during the study duration. * Prior exposure to classic psychedelics (i.e., psilocybin, LSD, ayahuasca, and/or mescaline) within the past 1 year. * Current or previous psychiatric conditions that meet DSM-5 criteria for psychotic disorders (i.e., schizophrenia, schizoaffective disorder, MDD with psychosis), bipolar 1 or 2 disorder, or current diagnosis of active substance use disorder. * Have active suicidal ideation with intent, based on Columbia-Suicide Severity Rating Scale (C-SSRS assessment (severity score \> 3) at the Screening visit, confirmed by the Investigator. * Have made a medically significant suicide attempt (i.e., one that had a significant possibility of causing death or permanent harm in the absence of intervention) within the past 12 months, based on Screening C-SSRS assessment and confirmation by the Investigator. * Immediate family history (i.e., parents, full siblings, or half siblings) with known or suspected psychotic disorder. * Presence of medical conditions that may confound results of imaging study or that are contraindications to or psilocybin exposure (i.e., neurological, renal, hypertension, metabolic or cardiovascular disease or pregnancy); * Presence of contraindications to MRI scanning (implantable devices, bone hardware, various IUD). * Participants who received electroconvulsive therapy (ECT), trans magnetic cranial stimulation (TMS), and/or ketamine in the past 90 days. * Has any other physical or psychological symptom, medication, or other relevant finding prior to randomization that, based on the clinical judgment of trial personnel, would make a participant unsuitable for the trial. * Are unable or unwilling to discontinue taking any protocol-prohibited medications and supplements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dimensional Anhedonia Rating Scale (DARS) Score | Baseline (Week -3), End of Study (Week 8) | DARS is a 17-item, patient-reported instrument designed to measure "state" anhedonia (how a person is feeling right now). The total score is the sum of responses and ranges from 0-68; lower scores indicate more severe anhedonia. |
| Change in Fronto-Striatal Connectivity (pgACC-NAcc FC) | Baseline (Week -3), End of Study (Week 8) | This outcome measures the change in functional connectivity (FC) between the pregenual anterior cingulate cortex (pgACC) and the nucleus accumbens (NAcc). PgACC-NAcc FC will be measured using fMRI sequencing. The standard deviation of FC is assumed to be 0.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Motivation and Pleasure Scale - Self-Report (MAP-SR) Score | Baseline (Week -3), End of Study (Week 8) | MAP-SR is an 15-item self-report assessment designed to measure the "experiential" negative symptoms of psychiatric disorders. Each item is rated on a scale from 0-4; the total score is the sum of responses and ranges from 0-60; lower scores indicate more severe psychiatric symptoms. |
| Change in Experiential Avoidance (BEAQ) Score | Baseline (Week -3), End of Study (Week 8) | The Brief Measure of Experimental Avoidance Questionnaire (BEAQ) is a 15-item assessment of experiential avoidance. Each item is rated on a scale from 1-6; the total score is the sum of responses and ranges from 15 to 90. Higher scores indicate greater levels of experiential avoidance (and lower psychological flexibility). |
| Change in Montgomery-Asberg Depression Scale (MADRS) Score | Baseline (Week -3), End of Study (Week 8) | The MADRS is a 10-item assessment of depression severity. Each item is rated on a scale from 0-6; the total score is the sum of responses and ranges from 0-60. Higher scores indicate greater severity of depression. |
Countries
United States
Contacts
CONTACTJulia Diamond
PRINCIPAL_INVESTIGATORJoshua Siegel, MD, PhD
NYU Langone Health
Outcome results
None listed