Lysergic Acid Diethylamide Occupancy of the Serotonin 2A Receptor in the Human Brain
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Plasma LSD - serotonin 2A receptor (5-HT2AR) occupancy relation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
Participants will be blinded with respect to dose only.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy individual between 18-75 years old
排除标准
- •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
研究组 & 干预措施
LSD dose-ranging group
All participants will receive between 25 and 200 micrograms of lysergic acid diethylamide equivalent as freebase, single blinded with respect to dose. Simultaneous PET/MR imaging will be performed during acute drug effects.
干预措施: Lysergic Acid Diethylamide Tartrate (Drug)
结局指标
主要结局
Plasma LSD - serotonin 2A receptor (5-HT2AR) occupancy relation
时间窗: Within 24 hours following drug administration
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.
次要结局
- fMRI brain entropy - 5-HT2AR occupancy relation(Within 24 hours following drug administration)
- Subjective drug intensity - 5-HT2AR occupancy relation(Within 24 hours following drug administration)
- fMRI network disintegration - 5-HT2AR occupancy relation(Within 24 hours following drug administration)
- Cerebral perfusion - 5-HT2AR occupancy relation(Within 24 hours following drug administration)
- Administered LSD dose - 5-HT2AR occupancy relation(Within 24 hours following drug administration)
研究者
Gitte Moos Knudsen
Professor, DMsc, MD
Rigshospitalet, Denmark