Role of the Serotonin 5-HT2A Receptor in LSD-induced Altered States of Consciousness (LDR-Study)

University Hospital Basel

Status and phase: Completed; Early Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: LSD

Study type: Interventional

Funder types: Other

Identifiers

NCT03321136

BASEC-2017-01348

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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16 participants in 6 patient groups, including a placebo group

Placebo, LSD-25, LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD

LSD-25, LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin, Placebo

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD

LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin, Placebo, LSD-25

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD

LSD-100, LSD-200, LSD-200-Ketanserin, Placebo, LSD-25, LSD-50

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD

LSD-200, LSD-200-Ketanserin, Placebo, LSD-25, LSD-50, LSD-100

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD

LSD-200-Ketanserin, Placebo, LSD-25, LSD-50, LSD-100, LSD-200

Placebo Comparator group

Description:

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Treatment:

Drug: LSD

Drug: LSD

Drug: LSD

Drug: LSD

Drug: Placebo

Drug: LSD