Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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)
    


Intervention name(s): Placebo; Mescaline 100mg; Mescaline 200mg; Mescaline 400mg; Mescaline 800mg; Mescaline 800mg + Ketanserin 40mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Drug: Placebo Capsules containing mannitol looking identical to the other drugs Other: Placebo Capsules containing mannitol looking identical to the other drugs; Drug: 100mg Mescaline per os, single dose
Other: Placebo (Capsules containing mannitol looking identical to the other drugs); Drug: 200mg Mescaline per os, single dose
Other: Placebo (Capsules containing mannitol looking identical to the other drugs); Drug: 400mg Mescaline per os, single dose
Other: Placebo (Capsules containing mannitol looking identical to the other drugs); Drug: 800mg Mescaline per os, single dose
Other: Placebo (Capsules containing mannitol looking identical to the other drugs); Drug: 800mg Mescaline per os, single dose
Other: 40mg Ketanserin per os, single dose
Intervention MeSH terms: Ketanserin; Mescaline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Mescaline; Serotonin; Hallucinogen