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

NCT03321136 | Completed Early Phase 1 DMC

• 1 other identifier: BASEC-2017-01348
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Altered states of consciousness

  total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)

  18 months

Secondary Outcomes (8)

• Subjective effects

  18 months

• Subjective effects

  18 months

• Psychotomimetic effects

  18 months

• Mystical-type experiences

  18 months

• Mystical-type experiences

  18 months

Study Arms (6)

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: LSD; Drug: Placebo

Interventions

LSD DRUG

0.025 mg LSD per os, single dose

Also known as: Lysergic Acid Diethylamide

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

Placebo DRUG

Capsules containing mannitol looking identical to the other drugs.

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

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital

Basel, 4031, Switzerland

Location

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

• Matthias E Liechti, MD, MAS

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: October 25, 2017
• Study Start: November 28, 2017
• Primary Completion: July 5, 2019
• Study Completion: July 11, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)