The Neurobiological Effect of 5-HT2AR Modulation

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Participant)
  • Study Primary Completion Date: December 31, 2019

Interventions

  • Drug: Psilocybine
    • Oral dose of psilocybin.
  • Drug: Ketanserin
    • Oral dose of ketanserin.

Arms, Groups and Cohorts

  • Other: Project 1
    • After baseline MRI & 5-HT2AR PET-imaging, participants will be allocated to undergo either one oral dose of psilocybin or one oral dose of ketanserin. After drug administration, participants will undergo two CIMBI-36 PET scans.
  • Other: Project 2
    • After baseline MRI & CIMBI-36 PET-imaging, participants will receive one dose of oral psilocybin. One and 12 weeks after dosing, participants will undergo post-intervention PET-scan.
  • Other: Project 3
    • After baseline MRI scanning and CIMBI-36 PET, participants will undergo one psilocybin-intervention fMRI scan and one ketanserin-intervention fMRI scan. If P2 shows there are long term effects of psilocybin on 5-HT2AR levels, psilocybin will be fixed as the second intervention. If not, interventions will be randomized.

Clinical Trial Outcome Measures

Primary Measures

  • Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential).
    • Time Frame: Change in Cimbi-36 binding potential from baseline PET to intervention PET 1 and PET 2 scans (same day for psilocybin, and two consecutive days for ketanserin).
    • The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.
  • Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks
    • Time Frame: Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).
    • Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.
  • Effects of psilocybin and ketanserin on brain function assessed with fMRI
    • Time Frame: Changes in functional connectivity (fMRI) from Baseline MR to intervention MR scans for ketanserin (one or three weeks after baseline MR) and psilocybin (one or three weeks after baseline)
    • Correlations between blood levels of ketanserin and psilocin and the estimated associated receptor occupancy with functional MRI neuroimaging data, including resting state networks

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Gitte Moos Knudsen
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Gitte Moos Knudsen, Professor, DMsc, MD – Rigshospitalet, Denmark
  • Overall Official(s)
    • Gitte M Knudsen, Professor, Study Chair, Neurobiology Research Unit, Rigshospitalet
  • Overall Contact(s)
    • Gitte M Knudsen, Professor, +45 35456720, gmk@nru.dk

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