The Neurobiological Effect of 5-HT2AR Modulation

NCT ID: NCT03289949

Last Updated: 2024-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-03

Study Completion Date

2030-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Basic Science

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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Project 1: Occupancy of psilocybin/ketanserin

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.

Group Type OTHER

Psilocybine

Intervention Type DRUG

Oral dose of psilocybine.

Ketanserin

Intervention Type DRUG

Oral dose of ketanserin.

Project 2: Long term effects of psilocybin

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.

Group Type OTHER

Psilocybine

Intervention Type DRUG

Oral dose of psilocybine.

Project 3: Functional connectivity

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.

Group Type OTHER

Psilocybine

Intervention Type DRUG

Oral dose of psilocybine.

Ketanserin

Intervention Type DRUG

Oral dose of ketanserin.

Interventions

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Psilocybine

Oral dose of psilocybine.

Intervention Type DRUG

Ketanserin

Oral dose of ketanserin.

Intervention Type DRUG

Other Intervention Names

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Psilocybin Ketensin

Eligibility Criteria

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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. Body weight under 50 kg.
17. Plasma ferritin levels outside normal range


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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Gitte Moos Knudsen

OTHER

Sponsor Role lead

Responsible Party

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Gitte Moos Knudsen

Professor, DMsc, MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Gitte M Knudsen, Professor

Role: STUDY_CHAIR

Neurobiology Research Unit, Rigshospitalet

Locations

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Neurobiology Research Unit, Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Gitte M Knudsen, Professor

Role: CONTACT

Phone: +45 35456720

Email: [email protected]

Patrick M Fisher, PhD

Role: CONTACT

Phone: +45 35456714

Email: [email protected]

Facility Contacts

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Gitte M Knudsen, Professor

Role: primary

Patrick M Fisher, PhD

Role: backup

Other Identifiers

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H-16026898

Identifier Type: -

Identifier Source: org_study_id