Evidence for tolerance in psychedelic microdosing from the self-blinding microdose trial

Introduction

Interest in therapeutic applications of classic psychedelics has grown sharply, with the best‑established model being psychedelic‑assisted therapy that pairs one or two supervised, moderate-to-high dose drug sessions with psychotherapy. A distinct and less-regulated practice, microdosing, has also become popular; although definitions vary, typical regimens involve very low doses taken 2–4 times per week (for example 5–20 µg LSD or 0.1–0.3 g dried psilocybin mushroom). Anecdotal reports and some observational studies claim benefits for mood, creativity and cognition, but placebo‑controlled trials have generally failed to find robust support for such effects, raising the possibility that reported benefits are driven by placebo or expectancy effects. Baumann and colleagues used data from their self‑blinding microdose trial to test whether tolerance develops during microdosing. The self‑blinding design is a citizen‑science, at‑home placebo‑controlled approach that allowed a large real‑world sample. The study specifically examined whether the probability of correctly guessing a microdose (used here as a proxy for noticeable subjective drug effects) declined as participants accumulated previous microdoses during the trial, and whether any tolerance effect differed between LSD/LSD‑analogues and psilocybin microdosing.