Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Psilocybin (Usona Institute), Risperidone 1 MG, MRI.
- Who it may be relevant to
- Registry conditions: Depression - Major Depressive Disorder, Anhedonia. Basic parameters: 18 years — 55 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Austria
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects: A Randomized, Open-Label, Cross-Over Functional Magnetic Resonance Imaging Trial
Overview
The goal of this clinical trial is to systematically categorize potential prohedonic effects of psilocybin in patients with anhedonia in depression. The main questions it aims to answer are: Primary Objectives 1. Systematically categorize prohedonic effects (antianhedonic effects in patients with anhedonia in depression, increase in well-being in all participants). 2. Test effects of psilocybin on brain network complexity measures during the hedonic experience using fMRI as a correlate for prohedonic (anti-anhedonic and well-being increasing) effects. 3. Elucidate relevance of the psychedelic experience to these effects (clinical, behavioral, and imaging) in a pharmacological challenge using the 5-HT2A/D2 antagonist risperidone and extensive characterization of the psychedelic experience. Secondary Objectives 4. Test the differential effects of the psychedelic experience on fMRI paradigms measuring symptoms shown to be altered in anhedonia, more specifically reward processing and sexual arousal. 5. Test the relevance of neuroplasticity (BDNF) and inflammatory parameters to anti-anhedonic, well-being promoting, and brain network dynamic complexity effects. 6. Test the effects of the psychedelic experience on BDNF and inflammatory parameters. Researchers will compare the effects of psilocybin in two separate sessions (one with psilocybin alone, one with co-administration of risperidone) in both patients with depression and anhedonia and healthy control participants. Participants will: * Take 25 mg of psilocybin p.o. in two sessions, in one of the two sessions they will take 1 mg risperidone p.o. before ingestion of psilocybin, to block psilocybin's acute psychedelic effects. * Undergo 3 MRI sessions, one before the first psilocybin session ('baseline') and one session each on the day after each respective psilocybin session. * Perform a variety of tasks during each fMRI session to asses the treatment's effects on anhedonia.
Interventions
- Drug Psilocybin (Usona Institute)
Participants will recieve two doses of Psilocybin 25 mg to be taken orally over the course of the study. - Drug Risperidone 1 MG
30 minutes before administration of psilocybin in one of the sessions to inhibit acute psychedelic effects - Diagnostic test MRI
Over the course of the study, participants will undergo three MRI measurement sessions. * M1 (baseline, before treatment) * M2 \& M3 (one day after each psilocybin session)
Primary outcome measures
- Aesthetic task [Time frame: From enrolment until the second assessment session (up to 9 weeks after enrolment)]
- Monetary Incentive Delay (MID) Task [Time frame: From enrolment until the last imaging session (up to 8 weeks after enrolment)]
- Sexual arousal task [Time frame: From enrolment until the last imaging session (up to 8 weeks after enrolment)]
- Cognitive Flexibility Inventory (CFI) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Intensity rating [Time frame: From enrolment until the second medication session (up to 8 weeks after enrolment)]
- Warwick-Edinburgh Mental Well-being Scale (WEMWBS) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Beck-Depression-Inventory (BDI) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Montgomery-Åsberg Depression Rating Scale (MADRS) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Dimensional Anhedonia Rating Scale (DARS) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Aesthetic Experiences Scale (AES) [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
Secondary outcome measures (4)
- Cytokine panel [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Brain-derived neurotrophic factor (BDNF) concentration [Time frame: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
- Neural activity [Time frame: Over the course of the three MRI sessions (3-14 days after enrolment, 1 day after the first medication session, 6 weeks after the second measurement)]
- Brain network dynamic complexity [Time frame: Over the course of the three MRI sessions (3-14 days after enrolment, 1 day after the first medication session, 6 weeks after the second measurement)]
Eligibility 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Austria · 1 center
- Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of Gene — Vienna
Identifiers
NCT: NCT07490353 · PSY-NIL-0016 · 2024-519265-22-00