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

NCT04849013 | Completed Phase 1

• 1 other identifier: BASEC 2021-00035
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Mescaline; Serotonin; Hallucinogen

Outcome Measures

Primary Outcomes (1)

• Altered States of Consciousness

  5 Dimensions of Altered States of Consciousness (5D-ASC) assesses mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. The questionnaire is consisting of 94 items to be rated on a visual analog scale (horizontal line, 100 mm, marked with "not at all" on the left and "extremely" on the right), with higher values indicating stronger effects. Subjects will mark the scale with vertical lines.

  18 months

Secondary Outcomes (28)

• Extent of subjective response over time

  18 months

• Subjective mood ratings

  18 months

• Subjective experiences of spiritual phenomenons

  18 months

• States of Consciousness

  18 months

• Mystical-type experiences

  18 months

Study Arms (6)

Placebo + Placebo

PLACEBO COMPARATOR

Drug: Placebo

Mescaline-100 + Placebo

ACTIVE COMPARATOR

Drug: Mescaline 100mg

Mescaline-200 + Placebo

ACTIVE COMPARATOR

Drug: Mescaline 200mg

Mescaline-400 + Placebo

ACTIVE COMPARATOR

Drug: Mescaline 400mg

Mescaline-800 + Placebo

ACTIVE COMPARATOR

Drug: Mescaline 800mg

Mescaline-800 + Ketanserin

ACTIVE COMPARATOR

Drug: Mescaline 800mg + Ketanserin 40mg

Interventions

Placebo DRUG

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

Placebo + Placebo

Mescaline 100mg DRUG

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

Mescaline-100 + Placebo

Mescaline 200mg DRUG

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

Mescaline-200 + Placebo

Mescaline 400mg DRUG

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

Mescaline-400 + Placebo

Mescaline 800mg DRUG

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

Mescaline-800 + Placebo

Mescaline 800mg + Ketanserin 40mg DRUG

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

Mescaline-800 + 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 old
• Sufficient understanding of the German language
• Understanding of procedures and risks associated with the study
• Willing to adhere to the protocol and signing of the consent form
• Willing to refrain from the consumption of illicit psychoactive substances during the study
• Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days
• Willing not to drive a traffic vehicle or operate heavy machinery within 48 hours after substance administration
• Willing to use double-barrier birth control throughout study participation
• Body mass index between 18-29 kg/m2

You may not qualify if:

• Chronic or acute medical condition
• Current or previous major psychiatric disorder
• Psychotic disorder or bipolar disorder in first-degree relatives
• Hypertension (\>140/90 mmHg) or hypotension (SBP10 cigarettes/day)
• Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
• Pregnancy or current breastfeeding
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medication that may interfere with the effects of the study medication
• Tobacco smoking (\>10 cigarettes/day)
• Consumption of alcoholic beverages (\>20 drinks/week)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, 4056, Switzerland

Location

Related Publications (1)

• Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, Schmid Y, Liechti ME. Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants. Clin Pharmacokinet. 2025 Oct;64(10):1495-1506. doi: 10.1007/s40262-025-01544-x. Epub 2025 Jul 14.

  PMID: 40658345 DERIVED

MeSH Terms

Interventions

Mescaline; Ketanserin

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Matthias E Liechti, Prof. Dr. MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: 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: March 26, 2021
• First Posted: April 19, 2021
• Study Start: August 11, 2021
• Primary Completion: March 27, 2023
• Study Completion: March 27, 2023
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)