The Neurobiological Effect of 5-HT2AR Modulation

Psilocybin

Brief Summary

The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools.

Intervention / Treatment

  • Psilocybine (DRUG)
    Oral dose of psilocybine.
  • Ketanserin (DRUG)
    Oral dose of ketanserin.

Condition or Disease

  • Basic Science

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Recruiting
    Study results: No Results Available
    Age: 18 Years and older   (Adult, Older Adult)
    Enrollment: 200 (ESTIMATED)
    Funded by: Other
    Allocation: Non-Randomized
    Primary Purpose: Basic Science

    Masking

    SINGLE:
    • Participant

    Clinical Trial Dates

    Start date: Mar 03, 2017 ACTUAL
    Primary Completion: Jun 01, 2027 ESTIMATED
    Completion Date: Jun 01, 2027 ESTIMATED
    Study First Posted: Sep 21, 2017 ACTUAL
    Results First Posted: Aug 30, 2020
    Last Updated: Aug 11, 2022

    Sponsors / Collaborators

    Lead Sponsor: Gitte Moos Knudsen
    Responsible Party: Gitte Moos Knudsen

    Location

    Copenhagen, Denmark

    This project applies an experimental medicine strategy coupled with human functional and molecular neuroimaging to elucidate the effects of 5-HT2A receptor (5-HT2AR) modulation on brain function and mood in healthy individuals. We compare psilocybin (5-HT2AR agonist) and ketanserin (5-HT2AR antagonist) effects on brain function to identify neural mechanisms mediating the clinical effects of psilocybin and, more broadly, to establish this comparative strategy as a pathway for delineating pharmacological effects on the brain in humans.

    Participant Groups

    • After baseline MRI \& 5-HT2AR PET-imaging, participants will be allocated to undergo either one oral dose of psilocybine or one oral dose of ketanserin. After drug administration, participants will undergo two CIMBI-36 PET scans.

    • After baseline MRI \& CIMBI-36 PET-imaging, participants will receive one dose of oral psilocybine intervention. One and 12 weeks after dosing, participants will undergo post-intervention PET-scan. Subproject B: After baseline MRI \& UCB-J PET-imaging, participants will receive one dose of oral psilocybine intervention. One week after dosing, participants will undergo post-intervention UCB-J PET-scan. Subproject C: After baseline MR imaging, participants will receive one dose of oral psilocybine (one of two doses: 3mg or \~0.3 mg/kg). One month after dosing, participants will undergo a post-intervention MRI scan.

    • After baseline MRI scanning and CIMBI-36 PET, participants will undergo one psilocybine-intervention fMRI scan and one ketanserin-intervention fMRI scan. If P2 shows there are long term effects of psilocybine on 5-HT2AR levels, psilocybine will be fixed as the second intervention. If not, interventions will be randomized.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    1) Healthy individuals above 18 years of age.

    Exclusion Criteria:

    1. Presence of or previous primary psychiatric disease (DSM axis 1 or WHO ICD-10 diagnostic classifications) or in first-degree relatives.
    2. Previous or present neurological condition/disease, significant somatic condition/disease or intake of drugs suspected to influence test results.
    3. Non-fluent Danish language skills.
    4. Vision or hearing impairment.
    5. Previous or present learning disability.
    6. Pregnancy.
    7. Breastfeeding.
    8. Contraindications in regard to MRI scanning.
    9. Alcohol or drug abuse.
    10. Allergy to test drugs.
    11. Participation in studies in which participant has received more than 10 mSv of radiation or other significant exposure to radiation.
    12. Abnormal ECG or intake of QT prolonging medication.
    13. Previous significant side-effects in regard to hallucinogenic drugs.
    14. Use of hallucinogenic drugs 6 months previous to inclusion.
    15. Blood donation 3 months before and after project participation
    16. Bodyweight under 50 kg.
    17. Plasma ferritin levels outside normal range

    This clinical trial is recruiting

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    Primary Outcomes

    • The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.

    • Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.

    • Correlations between blood levels of ketanserin and psilocin and the estimated associated receptor occupancy with functional MRI neuroimaging data, including resting state networks. Changes in synaptic density will be assessed with 11C-UCB-J PET scans before and 1 week after psilocybin intervention.

    • Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.

    • Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.

    More Details

    NCT Number: NCT03289949
    Other IDs: H-16026898
    Study URL: https://clinicaltrials.gov/study/NCT03289949
    Last updated: Sep 29, 2023