Role of the Serotonin 5-HT2A Receptor in LSD-induced Altered States of Consciousness (LDR-Study)
The present randomised crossover study (n=16) in healthy volunteers used escalating single oral doses of LSD (25–200 µg) with a placebo arm and a ketanserin (40 mg) pre-treatment to probe the role of the 5-HT2A receptor in LSD-induced altered states.
Detailed Description
This randomized, quadruple-masked, within-subject crossover study tested single oral doses of LSD (25, 50, 100, 200 µg), a 200 µg LSD plus ketanserin (40 mg) condition, and placebo in healthy volunteers to assess dose–response effects on altered states of consciousness.
Outcomes included subjective altered-state measures, safety and tolerability assessments, and physiological monitoring; ketanserin was used to pharmacologically probe the contribution of 5-HT2A receptors to high-dose LSD effects.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
LSD crossover
experimentalWithin-subject crossover including placebo and a ketanserin pre-treatment condition; six single-dose sessions per participant.
Interventions
- LSD25 µgvia Oral• single dose
Single dose 25 µg (0.025 mg).
- LSD50 µgvia Oral• single dose
Single dose 50 µg (0.05 mg).
- LSD100 µgvia Oral• single dose
Single dose 100 µg (0.1 mg).
- LSD200 µgvia Oral• single dose
Single dose 200 µg (0.2 mg).
- LSD200 µgvia Oral• single dose
200 µg LSD plus ketanserin 40 mg oral pre-dose.
- Placebovia Oral• single dose
Mannitol capsule placebo, visually identical.
Participants
Inclusion Criteria
- Inclusion Criteria:\n\n1. Age between 25 and 65 years.\n2. Understanding of the German language.\n3. Understanding the procedures and the risks associated with the study.\n4. Participants must be willing to adhere to the protocol and sign the consent form.\n5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.\n6. Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.\n7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.\n8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.\n9. Women of childbearing potential must be willing to use double-barrier birth control.\n10. Body mass index 18-29 kg/m2.
Exclusion Criteria
- Exclusion Criteria:\n\n1. Chronic or acute medical condition\n2. Current or previous major psychiatric disorder\n3. Psychotic disorder in first-degree relatives\n4. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.\n5. Pregnant or nursing women.\n6. Participation in another clinical trial (currently or within the last 30 days)\n7. Use of medications that may interfere with the effects of the study medications (any psychiatric medications)\n8. Tobacco smoking (>10 cigarettes/day)\n9. Consumption of alcoholic drinks (>10/week)