AnhedoniaPhase 1NCT07607938
Psilocybin as a Novel Therapy for Residual Anhedonia
A Phase 1 study testing Psilocybin in people with Anhedonia and Emotional Blunting, run by NYU Langone Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anhedonia, Emotional Blunting
- What is being tested?
- Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2026to 30 Sep 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
NYU Langone Health
New York, New York, 10016
About this study
Official title: Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia
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).
- Conditions
- Anhedonia, Emotional Blunting
- Being tested
- Psilocybin, Placebo
- Keywords
- SSRI, SNR, Depression, Anhedonia, Emotional Blunting, Psilocybin
- Medical subject headings
- Anhedonia, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
One-time dose of psilocybin 25 mg, oral, in capsule form.
PlaceboDrug
One-time dose of placebo (25 mg of inert filler), oral, in capsule form.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | Participants will complete a total of six MRI sessions; two sessions prior to psilocybin administration day and four sessions after.
On administration day, the psilocybin arm will receive psilocybin (25 mg single dose, under supervision). Receives: Drug: Psilocybin |
| Control | Placebo comparator | Participants will complete a total of six MRI sessions; two sessions prior to placebo administration day and four sessions after.
The control arm will receive placebo on administration day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Dimensional Anhedonia Rating Scale (DARS) Score
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.
Measured: Baseline (Week -3), End of Study (Week 8)
Change in Fronto-Striatal Connectivity (pgACC-NAcc FC)
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.
Measured: Baseline (Week -3), End of Study (Week 8)
Secondary outcomes (3)
Change in Motivation and Pleasure Scale - Self-Report (MAP-SR) Score
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.
Measured: Baseline (Week -3), End of Study (Week 8)
Change in Experiential Avoidance (BEAQ) Score
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).
Measured: Baseline (Week -3), End of Study (Week 8)
Change in Montgomery-Asberg Depression Scale (MADRS) Score
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.
Measured: Baseline (Week -3), End of Study (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study startSep 2026 (estimated)
- Primary completion1 Aug 2030 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnhedoniaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Joshua Siegel, MD, PhD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07607938
- Sponsor's protocol ID
- 26-00063
- Other IDs
- R01MH142698
- Status last verified
- Sep 2026
- First submitted
- 19 May 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified participant data from the final research dataset will be shared with researchers who provide a methodologically sound proposal, or investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose, beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Joshua Siegel, MD, PhD, Joshua.Siegel@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.