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

NCT ID: NCT04849013

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-11
• Study Completion Date: 2023-03-27

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo + Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Mescaline-100 + Placebo

Group Type: ACTIVE_COMPARATOR

Mescaline 100mg

Intervention Type: DRUG

Drug: 100mg Mescaline per os, single dose

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

Mescaline-200 + Placebo

Group Type: ACTIVE_COMPARATOR

Mescaline 200mg

Intervention Type: DRUG

Drug: 200mg Mescaline per os, single dose

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

Mescaline-400 + Placebo

Group Type: ACTIVE_COMPARATOR

Mescaline 400mg

Intervention Type: DRUG

Drug: 400mg Mescaline per os, single dose

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

Mescaline-800 + Placebo

Group Type: ACTIVE_COMPARATOR

Mescaline 800mg

Intervention Type: DRUG

Drug: 800mg Mescaline per os, single dose

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

Mescaline-800 + Ketanserin

Group Type: ACTIVE_COMPARATOR

Mescaline 800mg + Ketanserin 40mg

Intervention Type: DRUG

Drug: 800mg Mescaline per os, single dose

Other: 40mg Ketanserin per os, single dose

Interventions

Placebo

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

Intervention Type: DRUG

Mescaline 100mg

Drug: 100mg Mescaline per os, single dose

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

Intervention Type: DRUG

Mescaline 200mg

Drug: 200mg Mescaline per os, single dose

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

Intervention Type: DRUG

Mescaline 400mg

Drug: 400mg Mescaline per os, single dose

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

Intervention Type: DRUG

Mescaline 800mg

Drug: 800mg Mescaline per os, single dose

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

Intervention Type: DRUG

Mescaline 800mg + Ketanserin 40mg

Drug: 800mg Mescaline per os, single dose

Other: 40mg Ketanserin per os, single dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age between 25 and 65 years old

2. Sufficient understanding of the German language

3. Understanding of procedures and risks associated with the study

4. Willing to adhere to the protocol and signing of the consent form

5. Willing to refrain from the consumption of illicit psychoactive substances during the study

6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days

7. Willing not to drive a traffic vehicle or operate heavy machinery within 48 hours after substance administration

8. Willing to use double-barrier birth control throughout study participation

9. Body mass index between 18-29 kg/m2

Exclusion Criteria

1. Chronic or acute medical condition

2. Current or previous major psychiatric disorder

3. Psychotic disorder or bipolar disorder in first-degree relatives

4. Hypertension (>140/90 mmHg) or hypotension (SBP10 cigarettes/day)

5. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months

6. Pregnancy or current breastfeeding

7. Participation in another clinical trial (currently or within the last 30 days)

8. Use of medication that may interfere with the effects of the study medication

9. Tobacco smoking (>10 cigarettes/day)

10. Consumption of alcoholic beverages (>20 drinks/week)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias E Liechti, Prof. Dr. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 40658345 (View on PubMed)

Other Identifiers

BASEC 2021-00035

Identifier Type: -

Identifier Source: org_study_id