Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness

Summary

Mescaline (the active substance in Peyote and San Pedro cacti) is a classic and long known serotonergic psychedelic substance (hallucinogen) that is widely used for recreational, spiritual, and/or ethno medical purposes. Despite its long history, modern data on the acute effects of mescaline on human is lacking. Mescaline produces prototypical psychedelic effects, similar as lysergic acid diethylamide (LSD) and psilocybin. The serotonin 2A (5-HT2A) receptor is thought to primarily mediate acute alterations of consciousness induced by LSD and psilocybin. However, the contributory role of the 5-HT2A receptor in mescaline-induced alterations of consciousness is unclear. Using 5-HT2A receptor antagonist ketanserin, the psychedelic experience induced by LSD and psilocybin can be attenuated and shortened. The present study therefore explores the role the 5-HT2A receptor in mescaline-induced altered states of consciousness using escalating doses of mescaline and the 5-HT2A receptor blocker ketanserin administered before a high dose of mescaline.

Objective: The present MDR-study will characterize the subjective effects of different doses of mescaline using modern psychometric instruments and examine the contribution of the 5-HT2A receptor in the mescaline-induced alterations of consciousness.

Design: Double-blind, placebo-controlled, 6-period cross-over design with six treatment conditions. 1) Placebo (Pla + Pla), 2) 100 mg mescaline (Pla + 100mg mescaline), 3) 200 mg mescaline (Pla + 200mg mescaline), 4) 400 mg mescaline (Pla + 400mg mescaline), 5) 800 mg mescaline (Pla + 800mg mescaline), and 6) 40mg ketanserin and 800mg mescaline (Ket + 800mg mescaline).

Participants: 16 healthy participants aged ≥ 25 and ≤ 65 years (8 female, 8 male)

Conditions

• Healthy

Interventions

DRUG

Placebo

Drug: Placebo Capsules containing mannitol looking identical to the other drugs Other: Placebo Capsules containing mannitol looking identical to the other drugs

DRUG

Mescaline 100mg

Drug: 100mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

DRUG

Mescaline 200mg

Drug: 200mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

DRUG

Mescaline 400mg

Drug: 400mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

DRUG

Mescaline 800mg

Drug: 800mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

DRUG

Mescaline 800mg + Ketanserin 40mg

Drug: 800mg Mescaline per os, single dose Other: 40mg Ketanserin per os, single dose

Sponsors & Collaborators

• University Hospital, Basel, Switzerland

  lead OTHER

Principal Investigators

• Matthias E Liechti, Prof. Dr. MD · 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

2021-08-11

Primary Completion

2023-03-27

Completion

2023-03-27

Countries

• Switzerland

Study Locations