Study design
This study used a double-blind, placebo-controlled, crossover design with four experimental test sessions to investigate responses to (i) 300 mg or 500 mg mescaline, (ii) 100 µg LSD, (iii) 20 mg psilocybin, and (iv) placebo. The order of administration was random and counterbalanced. Washout periods in between sessions were at least 10 days. The mescaline dose was increased from 300 mg in participants 1–16 to 500 mg in participants 17–32 after it became apparent in the first few study sessions that the initially chosen 300 mg dose was most likely lower than the LSD and psilocybin doses. Hence, allocation to the substance conditions (mescaline, LSD, psilocybin or placebo) was always random and blinded whereas, in contrast, allocation to the 300 or 500 mg mescaline dose was neither randomized nor blinded (i.e. participants 1–16 were informed that they would receive 300 mg mescaline and participants 17–32 were informed that they would receive 500 mg mescaline). The study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Guidelines in Good Clinical Practice, and was approved by the Ethics Committee of Northwest Switzerland (EKNZ) and the Swiss Federal Office for Public Health. The study was registered at ClinicalTrials.gov (NCT04227756).