Clinical TrialHealthy VolunteersPsilocybinPlaceboPlaceboRecruiting

The Neurobiological Effect of 5-HT2AR Modulation

Non-randomised sequential experimental-medicine study (estimated n=200) using single oral doses of psilocybin and ketanserin to probe 5-HT2A receptor effects in healthy volunteers with PET and MRI outcomes.

Target Enrollment
200 participants
Study Type
Phase I interventional
Design
Non-randomized, single Blind

Detailed Description

This experimental medicine project compares psilocybin (5-HT2A agonist) and ketanserin (5-HT2A antagonist) effects on brain function using MRI and multiple PET tracers (CIMBI-36, UCB-J) in healthy volunteers.

Design includes sequential allocation across subprojects examining receptor occupancy, long-term effects (1 and 12 week follow-ups), and functional connectivity with single oral dosing (25 mg specified in one subproject) and repeated neuroimaging assessments.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin

experimental

Single oral psilocybin dose used across subprojects (25 mg specified in Subproject 2c).

Interventions

  • Psilocybin25 mg
    via Oral• single dose

    25 mg specified in Subproject 2c; other subprojects use a single oral dose (unspecified).

Ketanserin

active comparator

Oral 5-HT2A antagonist used for occupancy and fMRI comparisons.

Interventions

  • Placebo
    via Oral• single dose

    Ketanserin oral dose (unspecified) — encoded as non-listed active comparator.

Placebo

inactive

Oral placebo comparator used in Subproject 2c.

Interventions

  • Placebo
    via Oral• single dose

    Placebo oral capsule.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1) Healthy individuals above 18 years of age.

Exclusion Criteria

  • Exclusion Criteria (For Subprojects 1, 2a, 2b, and 3):
  • 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. Body weight under 50 kg.
  • 17. Plasma ferritin levels outside normal range
  • Exclusion Criteria (For Subproject 2c):
  • 1. Presence of or previous primary psychiatric disease (DSM IV axis 1 or WHO ICD-10 diagnostic classifications).
  • 2. Presence of or previous primary psychiatric disease with psychosis symptoms or hypomania (DSM IV axis 1 [drug/alcohol abuse/dependence, schizophrenia and other psychoses] or WHO ICD-10 diagnostic classifications [F10-29, as well as F30-39 with psychotic symptoms, F60]) in first-degree relatives (parents or siblings).
  • 3. Previous or present neurological condition/disease, significant somatic condition/disease or intake of drugs suspected to influence test results.
  • 4. Non-fluent Danish language skills or pronounced 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. Abnormal ECG or intake of QT prolonging medication.
  • 12. Previous significant side-effects in regard to hallucinogenic drugs.
  • 13. Previous use of hallucinogenic drugs.
  • 14. Body weight under 45 kg.
  • 15. Ethical concerns regarding the administration of a psychedelic drug.

Study Details

Locations

Neurobiology Research Unit, Rigshospitalet — Copenhagen, Denmark

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