NeuroPharm2: The Neurobiological Effect of 5-HT2AR Modulation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: 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. |
Drug: Psilocybine
Oral dose of psilocybine.
Other Names:
Drug: Ketanserin
Oral dose of ketanserin.
Other Names:
|
| Other: 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 (one of two doses: 3mg or ~0.3 mg/kg). One month after dosing, participants will undergo a post-intervention MRI scan. |
Drug: Psilocybine
Oral dose of psilocybine.
Other Names:
|
| Other: 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. |
Drug: Psilocybine
Oral dose of psilocybine.
Other Names:
Drug: Ketanserin
Oral dose of ketanserin.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential). [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 [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 and PET [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. Changes in synaptic density will be assessed with 11C-UCB-J PET scans before and 1 week after psilocybin intervention.
- Effects of psilocybin on UCB-J binding potential at baseline and at one week [Change in UCB-J binding potential from baseline to one week post psilocybin.]
Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.
- Effects of psilocybin on brain function assessed with fMRI at baseline and one month [Change in fMRI measures from baseline to one month post psilocybin]
Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Healthy individuals above 18 years of age.
Exclusion Criteria:
-
Presence of or previous primary psychiatric disease (DSM axis 1 or WHO ICD-10 diagnostic classifications) or in first-degree relatives.
-
Previous or present neurological condition/disease, significant somatic condition/disease or intake of drugs suspected to influence test results.
-
Non-fluent Danish language skills.
-
Vision or hearing impairment.
-
Previous or present learning disability.
-
Pregnancy.
-
Breastfeeding.
-
Contraindications in regard to MRI scanning.
-
Alcohol or drug abuse.
-
Allergy to test drugs.
-
Participation in studies in which participant has received more than 10 mSv of radiation or other significant exposure to radiation.
-
Abnormal ECG or intake of QT prolonging medication.
-
Previous significant side-effects in regard to hallucinogenic drugs.
-
Use of hallucinogenic drugs 6 months previous to inclusion.
-
Blood donation 3 months before and after project participation
-
Bodyweight under 50 kg.
-
Plasma ferritin levels outside normal range
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neurobiology Research Unit, Rigshospitalet | Copenhagen | Denmark | 2100 |
Sponsors and Collaborators
- Gitte Moos Knudsen
Investigators
- Study Chair: Gitte M Knudsen, Professor, Neurobiology Research Unit, Rigshospitalet
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-16026898