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

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

Interventions

DRUG

LSD

0.025 mg LSD per os, single dose

DRUG

LSD

0.05 mg LSD per os, single dose

DRUG

LSD

0.1 mg LSD per os, single dose

DRUG

LSD

0.2 mg LSD per os, single dose

DRUG

LSD

0.2 mg LSD plus 40 mg ketanserin per os, single doses each

DRUG

Placebo

Capsules containing mannitol looking identical to the other drugs.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland

  lead OTHER

Principal Investigators

• Matthias E Liechti, MD, MAS · University Hospital, Basel, Switzerland

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

25 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-11-28

Primary Completion

2019-07-05

Completion

2019-07-11

Countries

• Switzerland

Study Locations