LSD Occupancy of the Serotonin 2A Receptor in the Human Brain

Healthy participants will be administered one of a single dose of lysergic acid diethylamide (LSD) between 25 and 200 micrograms equivalent freebase. They will receive [11C]CIMBI-36 positron emission tomography (PET) scans at baseline and twice following LSD administration during peak and declining drug effects. PET scans will be acquired in a simultaneous PET/Magnetic Resonance Imaging (MRI) scanner which will also collect functional brain imaging data. Venous blood samples will be repeatedly drawn during acute drug effects for quantification of plasma LSD levels. Participants will also repeatedly rate their subjective drug intensity on a scale from 0 to 10 during acute drug effects. Together these data will inform the dose-binding relation of LSD at the serotonin (5-HT) 2A receptor, the primary site of action. This data will also inform the relation between 5-HT2A receptor binding by LSD and the induced subjective effects, as well as the effects on functional brain activity as measured with functional MRI.

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