Clinical trial NCT03321136: Role of the Serotonin 5-HT2A Receptor in LSD-induced Altered States of Consciousness (LDR-Study)
Official title: Role of the Serotonin 5-HT2A Receptor in LSD-induced Altered States of Consciousness (LDR-Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-10-25
Enrollment: 16
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Serotonin receptors, especially the 5HT2A receptor, are thought to be involved in the effects of various recreationally used psychedelic substances such as LSD. LSD potently stimulates the 5-HT2A receptor but also 5-HT2B/C, 5-HT1 and dopaminergic receptors. LSD induces acute transient alterations in waking consciousness including visual perceptual alterations, audio-visual synesthesia, derealization and depersonalization. LSD has therefore been used as experimental tool ("psychotomimetic") in modern psychiatric research to study psychotic-like states and model psychosis in healthy subjects \[1-5\]. However, the dose-effects of 5-HT2A receptor stimulation by LSD has not yet been studied. Additionally, there is still very limited data to what extent the 5HT2A receptor contributes to LSD's effects and its role in the mediation of the full response to LSD at a high dose is unclear. A recent experimental human study showed the 5-HT2A receptor antagonist ketanserin fully blocked the subjective effects of a moderate dose of 100 µg of LSD \[6\]. But, whether the effects of a high 200 µg oral dose of LSD can be blocked by the selective pharmacological 5-HT2A antagonist ketanserin remains to be tested to confirm the critical role of the 5-HT2A receptor in more pronounced alterations of consciousness and perception. The present study therefore explores the role the 5-HT2A receptor in LSD-induced altered states of consciousness using escalating doses of LSD and the 5-HT2A receptor blocker ketanserin administered before a high dose of LSD.


Eligibility criteria: Inclusion Criteria:

1. Age between 25 and 65 years.
2. Understanding of the German language.
3. Understanding the procedures and the risks associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. 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.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
9. Women of childbearing potential must be willing to use double-barrier birth control
10. Body mass index 18-29 kg/m2.

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder in first-degree relatives
4. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
5. Pregnant or nursing women.
6. Participation in another clinical trial (currently or within the last 30 days)
7. Use of medications that may interfere with the effects of the study medications (any psychiatric medications)
8. Tobacco smoking (\>10 cigarettes/day)
9. Consumption of alcoholic drinks (\>10/week)

Primary outcomes:
measure: Altered states of consciousness
timeFrame: 18 months
Secondary outcomes:
measure: Subjective effects
timeFrame: 18 months
measure: Subjective effects
timeFrame: 18 months
measure: Psychotomimetic effects
timeFrame: 18 months
measure: Mystical-type experiences
timeFrame: 18 months
measure: Mystical-type experiences
timeFrame: 18 months
measure: Autonomic effects
timeFrame: 18 months
measure: Autonomic effects
timeFrame: 18 months
measure: Autonomic effects
timeFrame: 18 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References: