Psilocybin to reduce loss of pleasure (anhedonia) in depression
Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects: A Randomized, Open-Label, Cross-Over Functional Magnetic Resonance Imaging Trial
This trial will test whether psilocybin, given alone or with a risperidone blockade, can reduce anhedonia and boost well‑being in adults with depression.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 85 (estimated) |
| Ages | 18 Years to 55 Years |
| Sex | All |
| Sponsor | Medical University of Vienna Academic / other |
| Locations | 1 site (Vienna, State of Vienna) |
| Trial ID | NCT07490353 on ClinicalTrials.gov |
What this trial studies
This Phase 1 interventional trial gives psilocybin to right‑handed, physically healthy adults (ages 18–55) with major depressive episodes marked by anhedonia and to matched healthy volunteers, with some sessions including a 5‑HT2A/D2 antagonist (risperidone). Functional MRI is used to measure brain network complexity and task responses during hedonic, reward, and sexual processing paradigms as neural correlates of prohedonic effects. The design combines clinical, behavioral, and imaging measures and compares effects when the psychedelic experience is pharmacologically blocked. Participants must be medication‑free and meet strict medical and psychiatric inclusion criteria at a single academic center in Vienna.
Who should consider this trial
Good fit: Ideal candidates are right‑handed adults aged 18–55 with a diagnosed major depressive episode and ICD‑10 anhedonia who are physically healthy, within a normal BMI range, and free of psychotropic medications.
Not a fit: People with current neurological disease, active medical illnesses, pregnancy/breastfeeding, ongoing antidepressant or other psychotropic use, left‑handedness, or who cannot travel to Vienna are unlikely to qualify or benefit from participation.
Why it matters
Potential benefit: If successful, the trial could identify brain and experiential markers tied to psilocybin's ability to restore pleasure, guiding safer and more targeted treatments for anhedonia in depression.
How similar studies have performed: Prior clinical work has shown promising antidepressant and prohedonic effects of psilocybin, but using risperidone as a pharmacological blockade combined with fMRI network complexity measures for anhedonia is a novel, mechanistic approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria: All participants: * General health based on medical history, physical examination, blood draw, and electrocardiogram * Age 18 to 55 years * Right-handedness (due to potential lateralization effects of left-handed subjects) * Willingness and competence to sign the informed consent form * Normal BMI weight range (18.5-24.9) Specific to healthy subjects: * Psychiatric health based on structured clinical interview for DSM-5 (SCID) * No concomitant medication Specific to anhedonia patients: * Major depressive episode (first or recurrent) based on structured clinical interview for DSM-5 (SCID) and ICD-10 * Fulfilling the ICD-10 diagnostic criterion of anhedonia * No concomitant medication, specifically also free of antidepressants or other psychopharmaceuticals (for at least 2 weeks, 5 weeks for fluoxetin) Exclusion criteria: All participants: * Current or history of neurological disease * Current medical illness requiring treatment * Pregnancy or current breastfeeding * Current or former substance dependency * Any contraindication for MRI * Failure to comply with the study protocol or to follow the instruction of the investigating team * Failure to confirm effective use of contraception in females at least 8 weeks before and after study participation each * First-degree relative with bipolar disorder or schizophrenia Specific to healthy subjects: \- Psychiatric diagnosis Specific to anhedonia patients: \- Psychiatric comorbidities excluding anxiety disorders and/or obsessive-compulsive disorders
Where this trial is running
Vienna, State of Vienna
- Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of General Psychiatry — Vienna, State of Vienna, Austria (Recruiting)
Study contacts
- Principal investigator: Marie Spies, Priv.-Doz. DDr. — Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of General Psychiatry
- Study coordinator: Marie Spies, Priv.-Doz. DDr.
- Email: marie.spies@meduniwien.ac.at
- Phone: +43 1 40400
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.