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

Healthy Clinical Trial

— LDR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03321136
• Other study ID #: BASEC-2017-01348
• Status: Completed
• Phase: Early Phase 1
• Start date: November 28, 2017
• Est. completion date: July 11, 2019

Study information

• Verified date: August 2019
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 11, 2019
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• LSD
0.025 mg LSD per os, single dose
• LSD
0.05 mg LSD per os, single dose
• LSD
0.1 mg LSD per os, single dose
• LSD
0.2 mg LSD per os, single dose
• LSD
0.2 mg LSD plus 40 mg ketanserin per os, single doses each
• Placebo
Capsules containing mannitol looking identical to the other drugs.

Locations

Country	Name	City	State
Switzerland	University Hospital	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Altered states of consciousness	total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)	18 months
Secondary	Subjective effects	VAS (Visual analog scales)	18 months
Secondary	Subjective effects	AMRS scales (Adjective mood rating scale)	18 months
Secondary	Psychotomimetic effects	ESI scale (Eppendorf Schizophrenia Inventory)	18 months
Secondary	Mystical-type experiences	MS scales (Mysticism scale)	18 months
Secondary	Mystical-type experiences	SCQ scales (States of consciousness questionnaire)	18 months
Secondary	Autonomic effects	Blood pressure	18 months
Secondary	Autonomic effects	Heart Rate	18 months
Secondary	Autonomic effects	Body temperature	18 months