Investigating the effects of serotonin receptor modulation on brain function

The Neurobiological Effect of 5-HT2AR Modulation

This study tests how two different substances, psilocybin and ketanserin, affect brain function and mood in healthy volunteers to better understand their impact on the brain.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rigshospitalet, Denmark (other)
• Drugs / interventions: radiation
• Locations: 1 site (Copenhagen)
• Trial ID: NCT03289949 on ClinicalTrials.gov

What this trial studies

This project explores the neurobiological effects of serotonin 2A receptor modulation in healthy volunteers by comparing the effects of psilocybin, a 5-HT2AR agonist, and ketanserin, a 5-HT2AR antagonist. Using advanced neuroimaging techniques such as MRI and PET, the study aims to elucidate how these substances influence brain function and mood. The goal is to identify the neural mechanisms underlying the clinical effects of psilocybin and establish a framework for understanding pharmacological impacts on the human brain.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy individuals over the age of 18 without a history of psychiatric or neurological disorders.

Not a fit: Patients with a history of psychiatric diseases, neurological conditions, or those who are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance our understanding of mood regulation and the therapeutic potential of psychedelics in treating mental health conditions.

How similar studies have performed: Other studies have shown promising results in understanding the effects of psychedelics on brain function, suggesting that this approach may yield valuable insights.

Eligibility 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.

Where this trial is running

Copenhagen

• Neurobiology Research Unit, Rigshospitalet — Copenhagen, Denmark (RECRUITING)

Study contacts

• Study coordinator: Gitte M Knudsen, Professor

Conditions: Basic Science