Clinical trial NCT04849013: Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
Official title: Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Mescaline
Serotonin
Hallucinogen
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2021-04-19
Enrollment: 16
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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)


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)

Primary outcomes:
measure: Altered States of Consciousness
timeFrame: 18 months
Secondary outcomes:
measure: Extent of subjective response over time
timeFrame: 18 months
measure: Subjective mood ratings
timeFrame: 18 months
measure: Subjective experiences of spiritual phenomenons
timeFrame: 18 months
measure: States of Consciousness
timeFrame: 18 months
measure: Mystical-type experiences
timeFrame: 18 months
measure: Blood pressure
timeFrame: 18 months
measure: Heart rate
timeFrame: 18 months
measure: Body temperature
timeFrame: 18 months
measure: Pupil size
timeFrame: 18 months
measure: Mescaline concentrations in the blood
timeFrame: 18 months
measure: Mescaline concentrations in the urine
timeFrame: 18 months
measure: Effects on brain-derived neurotrophic factor (BDNF)
timeFrame: 18 months
measure: Effects on inflammatory cytokines
timeFrame: 18 months
measure: Effects on oxytocin
timeFrame: 18 months
measure: Emotional effects
timeFrame: 18 months
measure: Effect moderation through personality traits I
timeFrame: 18 months
measure: Effect moderation through personality traits II
timeFrame: 18 months
measure: Effect moderation through personality traits III
timeFrame: 18 months
measure: Effect moderation through personality traits IV
timeFrame: 18 months
measure: Effect moderation through personality traits V
timeFrame: 18 months
measure: Psychological insight
timeFrame: 18 months
measure: Effects on life satisfaction, well-being and appreciation I
timeFrame: 18 months
measure: Effects on life satisfaction, well-being and appreciation II
timeFrame: 18 months
measure: Effects on life satisfaction, well-being and appreciation III
timeFrame: 18 months
measure: Effects on life satisfaction, well-being and appreciation IV
timeFrame: 18 months
measure: Incidence of Adverse Events before and during each study session
timeFrame: 18 months
measure: Incidence of Adverse Events during each study session
timeFrame: 18 months
measure: Electrical activity of the heart
timeFrame: 18 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Clinical Trial Unit
state: BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: