Basic Science Clinical Trial
— dOccLSOfficial title:
Lysergic Acid Diethylamide Occupancy of the Serotonin 2A Receptor in the Human Brain
The investigators wish to quantify the relation between administered dose of lysergic acid diethylamide (LSD), plasma LSD levels, and occupancy at the serotonin 2A receptor (5-HT2AR) using [11C]CIMBI-36 positron emission tomography.
Status | Recruiting |
Enrollment | 40 |
Est. completion date | December 2024 |
Est. primary completion date | June 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: • Healthy individual between 18-75 years old Exclusion Criteria: - Current or past history of primary psychiatric illness (The Diagnostic and Statistical Manual of Mental Disorders IV axis-I or World Health Organisation International Classification of Diseases-10 diagnostic classification) - Current or past history of primary psychiatric illness (The Diagnostic and Statistical Manual of Mental Disorders IV axis-I or World Health Organisation International Classification of Diseases-10 diagnostic classification) in a first degree relative (i.e., parents, siblings) - Current or past history of neurological disease, significant somatic condition/disease - Use of medication that could potentially influence results (e.g.., drugs that act on relevant components of the serotonin system or may interfere with metabolism of study drug) - Non-fluent Danish language skills - Profound visual or auditory impairments - Severe learning disability - Pregnancy on the scan date, verified by a pregnancy test (test omitted if confirmed that individual is post-menopausal) - Lactation (females) - Contraindications for magnetic resonance imaging (e.g., pacemaker, claustrophobia, etc.) - Contraindications for positron emission tomography - Alcohol or drug abuse - Allergy to administered compounds - Participant in research study with >10 millisievert exposure within the past year or significant occupational exposure to radioactive substances - Abnormal ECG (ECG indicating current or previous heart disease or predisposition to heart disease, e.g., QT prolongation) or use of QT prolonging medication - Use of psychedelic substance within the preceding six months - Blood donation up to three months before the study (i.e., more than 500ml of blood) - Head injury or concussion resulting in loss of consciousness for more than 2 min - Haemoglobin levels < 7.8 mmol/l for women and 8.4 mmol/l for men - Ferritin levels outside normal range (12-300 µg/L) - Body-weight < 50 kg or > 110kg - body-mass index > 35 - Individual assessment by research staff deeming drug administration unsafe due to ethical or psychological circumstance of the participant |
Country | Name | City | State |
---|---|---|---|
Denmark | Neurobiology Research Unit, Rigshospitalet | Copenhagen |
Lead Sponsor | Collaborator |
---|---|
Rigshospitalet, Denmark |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Hysteresis effect of 5-HT2AR binding | Estimated dose-occupancy curves derived from the first PET scan and second PET scan will be calculated separately to evaluate whether there are differences in estimated plasma level-occupancy relation at different timepoints following LSD administration which may indicate a hysteresis effect due to peripheral LSD metabolism without unbinding of LSD from the 5-HT2A receptor. | Within 24 hours following drug administration | |
Primary | Plasma LSD - serotonin 2A receptor (5-HT2AR) occupancy relation | Occupancy will be estimated by comparing non-displaceable binding potential (BPND) values using baseline and intervention rescans as calculated using a simplified reference tissue model (SRTM). Occupancy values will be compared to plasma lysergic acid diethylamide (LSD) levels. | Within 24 hours following drug administration | |
Secondary | Subjective drug intensity - 5-HT2AR occupancy relation | Occupancy will be calculated as described above. Subjective drug intensity is collected during positron emission tomography (PET) scans by asking participants. | Within 24 hours following drug administration | |
Secondary | fMRI network disintegration - 5-HT2AR occupancy relation | functional magnetic resonance imaging (fMRI) data will be used to estimate functional-network connectivity using a standard functional brain atlas. Then the relation between decreases in functional network connectivity and 5-HT2AR occupancy will be estimated. | Within 24 hours following drug administration | |
Secondary | fMRI brain entropy - 5-HT2AR occupancy relation | fMRI brain entropy will be estimated by the shannon entropy of dynamic conditional correlation of within and between network connectivity as well as the lempel-ziv complexity of concatenated binarised blood-oxygen level dependent (BOLD) signals across regions. The relation between each of these measures with 5-HT2AR occupancy will be estimated. | Within 24 hours following drug administration | |
Secondary | Cerebral perfusion - 5-HT2AR occupancy relation | Cerebral perfusion will be estimated using arterial spin labelling. The relation between this measure and 5-HT2AR occupancy will be estimated. | Within 24 hours following drug administration | |
Secondary | Administered LSD dose - 5-HT2AR occupancy relation | Administered dose (25 to 200 mcg) will be compared with peak LSD occupancy to determine what doses produce maximal occupancy at the 5-HT2AR. | Within 24 hours following drug administration |
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