Clinical TrialHealthy VolunteersPlaceboMescalineMescalineMescalineMescalineMescalinePlaceboCompleted

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

Double-blind, placebo-controlled, 6-period crossover study (n=16) evaluating escalating oral mescaline doses (100–800 mg) and ketanserin pre-treatment in healthy volunteers aged 25–65.

Target Enrollment
16 participants
Study Type
Phase I interventional
Design
Randomized, quadruple Blind

Detailed Description

This randomized, quadruple-blind, placebo-controlled crossover study characterises subjective and psychometric effects of escalating oral mescaline doses (100, 200, 400, 800 mg) in healthy volunteers and examines the contribution of the 5-HT2A receptor using ketanserin pre-treatment.

Six treatment conditions are administered across separate single-dose sessions with washouts; outcomes include acute subjective measures, pharmacodynamics and safety assessments to determine the role of 5-HT2A signalling in mescaline-induced altered states.

Study Protocol

Preparation

sessions

Dosing

6 sessions

Integration

sessions

Study Arms & Interventions

Placebo + Placebo

inactive

Placebo capsules in both pre-treatment and challenge periods.

Interventions

  • Placebo mg
    via Oral• single dose

    Placebo capsules containing mannitol (pre-treatment and challenge).

Mescaline 100 mg

experimental

100 mg oral mescaline with placebo pre-treatment.

Interventions

  • Mescaline100 mg
    via Oral• single dose

    100 mg oral mescaline; placebo pre-treatment.

Mescaline 200 mg

experimental

200 mg oral mescaline with placebo pre-treatment.

Interventions

  • Mescaline200 mg
    via Oral• single dose

    200 mg oral mescaline; placebo pre-treatment.

Mescaline 400 mg

experimental

400 mg oral mescaline with placebo pre-treatment.

Interventions

  • Mescaline400 mg
    via Oral• single dose

    400 mg oral mescaline; placebo pre-treatment.

Mescaline 800 mg

experimental

800 mg oral mescaline with placebo pre-treatment.

Interventions

  • Mescaline800 mg
    via Oral• single dose

    800 mg oral mescaline; placebo pre-treatment.

Ketanserin + Mescaline 800 mg

experimental

40 mg oral ketanserin given before 800 mg oral mescaline to probe 5-HT2A contribution.

Interventions

  • Mescaline800 mg
    via Oral• single dose

    800 mg oral mescaline.

  • Placebo40 mg
    via Oral• single dose

    Ketanserin 40 mg oral pre-treatment (active antagonist; coded as non-listed comparator).

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Age between 25 and 65 years
  • 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
  • 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)

Study Details

Locations

University Hospital Basel, Clinical Trial Unit — Basel, Canton of Basel-City, Switzerland

Related Publications

Open Accessindividual

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects

This randomised, double-blind, placebo-controlled, crossover study (n=16) investigates the dose-dependent acute effects, pharmacokinetics, and mechanism of action of mescaline (100-800mg; 5x) in healthy subjects. It finds that mescaline induces dose-dependent subjective effects, increases blood pressure and heart rate, and has dose-proportional pharmacokinetics, with effects primarily mediated by 5-HT2A receptors as demonstrated by ketanserin co-administration.

Published
Journal
Translational Psychiatry
Authors
Becker, A. M., Erne, L., Jelusic, A., Klaiber, A., Liechti, M. E., Luethi, D., Schmid, Y., Straumann, I., Thomann, J.

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