The Neurobiological Effect of 5-HT2AR Modulation (NeuroPharm2)

Gitte Moos Knudsen

Status and phase: Enrolling; Phase 1

Conditions: Basic Science

Treatments: Drug: Psilocybine; Drug: Ketanserin

Study type: Interventional

Funder types: Other

Identifiers

NCT03289949

H-16026898

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Healthy individuals above 18 years of age.

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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200 participants in 3 patient groups

Project 1: Occupancy of psilocybin/ketanserin

Other group

Description:

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.

Treatment:

Drug: Ketanserin

Drug: Psilocybine

Project 2: Long term effects of psilocybin

Other group

Description:

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 (25 mg) or placebo. One month after dosing, participants will undergo a post-intervention MRI scan.

Treatment:

Drug: Psilocybine

Project 3: Functional connectivity

Other group

Description:

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.

Treatment:

Drug: Ketanserin

Drug: Psilocybine