The Neurobiological Effect of 5-HT2AR Modulation

NCT03289949 | Recruiting Phase 1 DMC

• 1 other identifier: H-16026898
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Basic Science

Outcome Measures

Primary Outcomes (12)

• Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential).

  The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.

  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).

• Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks

  Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.

  Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).

• Effects of psilocybin and ketanserin on brain function assessed with fMRI and PET

  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.

  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)

• Effects of psilocybin on UCB-J binding potential at baseline and at one week

  Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.

  Change in UCB-J binding potential from baseline to one week post psilocybin.

• Effects of psilocybin on brain function assessed with fMRI at baseline and one month

  Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.

  Change in fMRI measures from baseline to one month post psilocybin

• Anxiety Outcome Measure 1: Acute psychological effects as assessed using Challenging Experiences Questionnaire (CEQ).

  Differences in CEQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely; More than ever). Higher scores thus reflect a more challenging experience. Project 2, Subproject C. PsiloZonic.

  Immediately post-intervention.

• Anxiety Outcome Measure 2: Acute psychological effects as assessed using 5D-Altered States of Consciousness (5D-ASC) scale.

  Differences in 5D-ASC anxiety scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Visual analogue scale (VAS) scale ranging from 0 (No, not more than usually) to 100 (Yes, much more than usually). Higher scores on dimension anxiety thus reflect more anxiety. Project 2, Subproject C. PsiloZonic.

  Immediately post-intervention.

• Anxiety Outcome Measure 3: Acute psychological effects as assessed using Extended Subjective Drug Intensity (eSDI) scale.

  Differences in eSDI anxiety scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 10 (Very much). Higher scores on item anxiety thus reflect more anxiety. Project 2, Subproject C. PsiloZonic.

  During intervention.

• Transformative Experiences Outcome Measure 1: Acute psychological effects as assessed using Mystical Type Experiences Questionnaire (MEQ) scale.

  Differences in MEQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect a more profound mystical type experience. Project 2, Subproject C. PsiloZonic.

  Immediately post-intervention.

• Transformative Experiences Outcome Measure 2: Acute psychological effects as assessed using Psychological Insights Questionnaire (PIQ) scale.

  Differences in PIQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect more psychological insight. Project 2, Subproject C. PsiloZonic.

  Immediately post-intervention.

• Transformative Experiences Outcome Measure 3: Acute psychological effects as assessed using Emotional Breakthrough Questionnaire (EBI) scale.

  Differences in EBI scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Visual analogue scale (VAS) scale ranging from 0 (No, not more than usually) to 100 (Yes, much more than usually). Higher scores thus reflect more emotional breakthrough. Project 2, Subproject C. PsiloZonic.

  Immediately post-intervention.

• Persisting Effects Outcome Measure 1: Persisting psychological effects as assessed using Persisting Effects Questionnaire (PEQ) scale.

  Differences in PEQ scores will be assessed between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect more persisting effects. Project 2, Subproject C. PsiloZonic.

  One and three months post-intervention.

Study Arms (3)

Project 1: Occupancy of psilocybin/ketanserin

OTHER

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; Drug: Ketanserin

Project 2: Long term effects of psilocybin

OTHER

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.

Drug: Psilocybine

Project 3: Functional connectivity

OTHER

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; Drug: Ketanserin

Interventions

Psilocybine DRUG

Oral dose of psilocybine.

Also known as: Psilocybin

Project 1: Occupancy of psilocybin/ketanserin; Project 2: Long term effects of psilocybin; Project 3: Functional connectivity

Ketanserin DRUG

Oral dose of ketanserin.

Also known as: Ketensin

Project 1: Occupancy of psilocybin/ketanserin; Project 3: Functional connectivity

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Healthy individuals above 18 years of age.

You may not qualify if:

• 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.
• Blood donation 3 months before and after project participation
• Body weight under 50 kg.

Sponsors & Collaborators

• Gitte Moos Knudsen: lead

Study Sites (1)

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Interventions

Psilocybin; Ketanserin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Piperidines; Heterocyclic Compounds, 1-Ring; Quinazolinones; Quinazolines

Study Officials

• Gitte M Knudsen, Professor

  Neurobiology Research Unit, Rigshospitalet

  STUDY CHAIR

Central Study Contacts

Gitte M Knudsen, Professor

CONTACT

+45 35456720; gmk@nru.dk

Patrick M Fisher, PhD

CONTACT

+45 35456714; patrick.fisher@nru.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMsc, MD

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 21, 2017
• Study Start: March 3, 2017
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Upon project completion
• Access Criteria: All researchers can request access to data from the database by completing a standardized application form to provide detailed information about the specific database request. The application form and guidelines are available here. Please note that there are some formal requirements that must be fulfilled if the data request is from an international researcher. For example we do not have permission for sharing data outside of the EU, so researchers from a non-EU country will have to come here to work on the data instead.

Locations

DK (1)