Comparative Acute Effects of LSD, Psilocybin and Mescaline
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      LSD, psilocybin and mescaline are widely used for recreational and ethnomedical purposes. All
      three substances are thought to induce prototypical psychedelic effects primarily via
      stimulation of the 5-HT2A receptor. However, there are differences in the substances'
      molecular structures and receptor activation profiles which may induce differential
      subjective effects. To date, there are no modern studies comparing LSD, psilocybin and
      mescaline directly within the same clinical study and research subjects using validated
      psychometric tools. Therefore, the LPM-Study compares the acute effects of LSD, psilocybin,
      mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design with
      four treatment conditions: 1) 100 μg LSD, 2) 20 mg psilocybin, 3) 300 or 500 mg mescaline,
      and 4) placebo.
    

Detailed description: 
      LSD (lysergic acid diethylamide), psilocybin (the active substance in "magic mushrooms") and
      mescaline (the active substance in Peyote and San Pedro cacti) are serotonergic hallucinogens
      widely used for recreational and/or ethnomedical purposes. LSD, psilocybin and mescaline are
      thought to induce prototypical psychedelic effects primarily via stimulation of the 5-HT2A
      receptor. However, there are differences in their molecular structures (LSD: ergoline,
      psilocybin: tryptamine; mescaline: phenethylamine)and receptor activation profiles which may
      induce different subjective effects. To date, there are no modern studies comparing these
      three substances directly within the same clinical study and research subjects using
      validated psychometric tools. Therefore, the LPM-Study compares the acute effects of LSD,
      psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over
      design with four treatment conditions: 1) 100 μg LSD, 2) 20 mg psilocybin, 3) 300 or 500 mg
      mescaline, and 4) placebo. The main objective of this study is to determine whether LSD,
      psilocybin and mescaline produce qualitatively similar subjective alterations of mind and
      associated brain activity patterns despite their unique receptor activation profiles. The
      study investigates psychological (psychometry), physiological and neuronal (magnetic
      resonance imaging) variables. The LPM-Study provides insight into the acute effects profiles
      of three serotonergic hallucinogens. It will enhance the understanding of psychedelic-induced
      altered states of consciousness in humans and will be relevant for the fields of psychiatry,
      psychology, and forensic toxicology.
    

Intervention name(s): LSD; Psilocybin; Mescaline; Placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): LSD 0.1 mg per os, single dose OR Psilocybin 20 mg per os, single dose OR Mescaline 300 mg per os, single dose OR Placebo; Psilocybin 20 mg per os, single dose; Mescaline 300 mg or 500 mg per os, single dose; Placebo (Mannitol)
Intervention MeSH terms: Psilocybin; Mescaline
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science