This double-blind, placebo-controlled, 6-period crossover study (n=16) evaluated escalating oral mescaline doses (100–800 mg) and ketanserin pre-treatment in healthy volunteers aged 25–65.
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.
Placebo capsules in both pre-treatment and challenge periods.
Placebo capsules containing mannitol (pre-treatment and challenge).
100 mg oral mescaline with placebo pre-treatment.
100 mg oral mescaline; placebo pre-treatment.
200 mg oral mescaline with placebo pre-treatment.
200 mg oral mescaline; placebo pre-treatment.
400 mg oral mescaline with placebo pre-treatment.
400 mg oral mescaline; placebo pre-treatment.
800 mg oral mescaline with placebo pre-treatment.
800 mg oral mescaline; placebo pre-treatment.
40 mg oral ketanserin given before 800 mg oral mescaline to probe 5-HT2A contribution.
800 mg oral mescaline.
Ketanserin 40 mg oral pre-treatment (active antagonist; coded as non-listed comparator).
This pooled analysis of two double‑blind, randomized, placebo‑controlled studies (48 participants, 96 administrations) found that single oral doses of mescaline 100–800 mg produced dose‑dependent increases in positive subjective effects with only moderate autonomic changes and no clinically significant liver, kidney or haematological abnormalities. Although nausea was dose‑limiting and small proportions experienced transient diastolic hypertension, tachycardia, fever or “flashbacks”, single doses up to 800 mg were considered safe with respect to acute psychological and physical harm in healthy participants in a controlled clinical setting.