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

NCT05953038 | Active Not Recruiting Early Phase 1

• 2 other identifiers: H-210600562021-002633-42
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Basic Science

Keywords

Lysergic acid diethylamide; PET; Psychedelic; Hallucinogen; Physiological Effects of Drugs; Psychotropic Drugs; Ergolines; Serotonin; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• fMRI brain entropy - 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

Other Outcomes (1)

• Hysteresis effect of 5-HT2AR binding

  Within 24 hours following drug administration

Study Arms (1)

LSD dose-ranging group

EXPERIMENTAL

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.

Drug: Lysergic Acid Diethylamide Tartrate

Interventions

Lysergic Acid Diethylamide Tartrate DRUG

D-Lysergic Acid Diethylamide (LSD) D-tartrate as oral drinking solution (water / ethanol 20% m/m)

Also known as: LSD, d-LSD, LSD-25

LSD dose-ranging group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy individual between 18-75 years old

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Links

• Lab study homepage

MeSH Terms

Interventions

Lysergic Acid Diethylamide

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gitte M Knudsen, DMsc, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Participants will be blinded with respect to dose only.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, DMsc, MD

Model Details: Each participant will be given one of 25, 50, 75, 100, 125, 150, 175 or 200 micrograms of lysergic acid diethylamide (LSD) equivalent as freebase.

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: July 19, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): December 18, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)