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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: LSD; Drug: LSD; Drug: LSD; Drug: LSD; Drug: LSD

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo, LSD-25, LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide
Placebo Comparator: LSD-25, LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin, Placebo; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide
Placebo Comparator: LSD-50, LSD-100, LSD-200, LSD-200-Ketanserin, Placebo, LSD-25; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide
Placebo Comparator: LSD-100, LSD-200, LSD-200-Ketanserin, Placebo, LSD-25, LSD-50; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide
Placebo Comparator: LSD-200, LSD-200-Ketanserin, Placebo, LSD-25, LSD-50, LSD-100; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide
Placebo Comparator: LSD-200-Ketanserin, Placebo, LSD-25, LSD-50, LSD-100, LSD-200; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.; Drug: LSD; 0.025 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.05 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.1 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: LSD; 0.2 mg LSD plus 40 mg ketanserin per os, single doses each; Other Names: Lysergic Acid Diethylamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altered states of consciousness	total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects	VAS (Visual analog scales)	18 months
Subjective effects	AMRS scales (Adjective mood rating scale)	18 months
Psychotomimetic effects	ESI scale (Eppendorf Schizophrenia Inventory)	18 months
Mystical-type experiences	MS scales (Mysticism scale)	18 months
Mystical-type experiences	SCQ scales (States of consciousness questionnaire)	18 months
Autonomic effects	Blood pressure	18 months
Autonomic effects	Heart Rate	18 months
Autonomic effects	Body temperature	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, MAS, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): July 11, 2019

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; Lysergic Acid Diethylamide
• Other Study ID Numbers: BASEC-2017-01348

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No