LSD, Psilocybin, and Mescaline Acute Effects to be Directly Compared in First Modern Double-Blind Crossover Clinical Study

Despite widespread recreational and ethnomedical use of LSD, psilocybin, and mescaline, and their shared primary mechanism via 5-HT2A receptor stimulation, no modern clinical study has directly compared their acute subjective effects within the same individuals using validated psychometric tools. While all three substances are considered prototypical psychedelics, their distinct molecular structures and varying receptor activation profiles (which extend beyond just 5-HT2A to include other monoamine receptors) suggest they may induce subtle yet significant differences in subjective experience, emotional processing, and cognitive effects. This critical knowledge gap hinders a precise understanding of their comparative pharmacology and the optimization of their potential therapeutic applications for various psychiatric conditions, where specific experiential profiles might be more beneficial.

The LPM-Study is designed as a rigorous double-blind, placebo-controlled, 4-period crossover clinical trial, ensuring each participant serves as their own control. The study will administer four distinct treatment conditions: a single oral dose of 100 μg LSD, 20 mg psilocybin, 300 or 500 mg mescaline, and a placebo. The primary objective is to systematically assess and compare the acute subjective effects of these classic psychedelics using a battery of validated psychometric tools and questionnaires, allowing for a robust, within-subject comparison of their pharmacological profiles.