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

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Mescaline 400mg; Drug: Placebo; Drug: Mescaline 200mg; Drug: Mescaline 800mg; Drug: Mescaline 800mg + Ketanserin 40mg; Drug: Mescaline 100mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04849013

BASEC 2021-00035

Details and patient eligibility

About

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)

Enrollment: 16 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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16 participants in 6 patient groups, including a placebo group

Placebo + Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Mescaline-100 + Placebo

Active Comparator group

Treatment:

Drug: Mescaline 100mg

Mescaline-200 + Placebo

Active Comparator group

Treatment:

Drug: Mescaline 200mg

Mescaline-400 + Placebo

Active Comparator group

Treatment:

Drug: Mescaline 400mg

Mescaline-800 + Placebo

Active Comparator group

Treatment:

Drug: Mescaline 800mg

Mescaline-800 + Ketanserin

Active Comparator group

Treatment:

Drug: Mescaline 800mg + Ketanserin 40mg