The Neurobiological Effect of 5-HT2AR Modulation

Basic Science Clinical Trial

— NeuroPharm2  

Official title:

The Neurobiological Effect of 5-HT2AR Modulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03289949
• Other study ID #: H-16026898
• Status: Recruiting
• Phase: Phase 1
• Start date: March 3, 2017
• Est. completion date: June 1, 2027

Study information

• Verified date: October 2023
• Source: Rigshospitalet, Denmark
• Contact: Gitte M Knudsen, Professor
• Phone: +45 35456720
• Email: gmk[@]nru.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Basic Science

Intervention

Drug:
• Psilocybine
Oral dose of psilocybine.
• Ketanserin
Oral dose of ketanserin.

Locations

Country	Name	City	State
Denmark	Neurobiology Research Unit, Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Gitte Moos Knudsen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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)
Primary	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.
Primary	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
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.