Psilocybin to reduce loss of pleasure (anhedonia) in depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.