A RIGOROUS DOUBLE-BLIND RANDOMIZED-CONTROLLED TRIAL ON MICRODOSING PSILOCYBIN OVER EIGHT WEEKS

Abstract

While microdosing psilocybin—the practice of taking very small, non-hallucinogenic doses— has become more popular recently, especially for mood enhancement, there is a paucity of rigorous clinical research on its effects. This dissertation explores the therapeutic potential of microdosing psilocybin for treating symptoms of depression and anxiety and improving quality of life, addressing critical gaps in the literature surrounding its efficacy and mechanism of action. We conducted a phase II randomized controlled trial (RCT) involving 20 participants diagnosed with mild-to-moderate Major Depressive Disorder. Participants were assigned to either a psilocybin-first microdosing regimen (2 mg weekly) or placebo-first for four weeks, followed by an open-label crossover phase with 2mg of psilocybin for four additional weeks. The study assessed changes in multiple cognitive, state, and trait depressive symptoms, as well as anxiety and quality of life, using a comprehensive battery gold-standard measures. Findings revealed that while the microdosing regimen assessed here did not significantly reduce depressive symptoms, it had a significant positive impact on symptoms of anxiety and quality of life. Furthermore, we found that while participants were significantly better than chance at detecting whether they were in the psilocybin condition, they were still technically and legally unimpaired. Taken together, this research suggests that microdosing may be an effective treatment to symptoms of anxiety, and that the most accurate definition for microdosing is not a “sub-perceptual”, but rather an "unimpairing" dose. These promising results should be followed by additional data collection in larger trials to confirm or falsify our findings.