Melbourne-based MindBio Therapeutics recently released top-line results from a Phase 2B trial testing low-dose LSD against major depressive disorder, showing that the psychedelic substance was outperformed by a placebo. The eight-week study involved eighty-nine adult patients whose depressive symptoms were tracked using the recognized Montgomery-Åsberg Depression Rating Scale (MADRS). This outcome directly contrasts with widespread anecdotal endorsements that positioned microdosing as a potent, non-hallucinogenic mood enhancer.
MindBio CEO Justin Hanka publicized the findings via LinkedIn, framing the research as the "most vigorous placebo controlled trial ever performed in microdosing." The trial administered LSD doses ranging from four to twenty micrograms, amounts deliberately kept below the psychoactive threshold. Despite this, participants receiving the microdose reported some subjective upticks in well-being.
However, the crucial metric, the MADRS score, favored the control group receiving the placebo. Researchers employed a caffeine pill as the active placebo, a common practice in psychedelic research to account for expectation bias. Patients in these trials often anticipate a psychoactive effect, necessitating a control substance with known, albeit mild, psychoactive properties.
Microdosing, the practice of consuming minute quantities of substances like psilocybin or LSD, gained significant traction in technology circles over the past decade. Proponents suggested benefits ranging from enhanced focus to reduced depressive symptoms, often citing personal testimonials.
This new data, which has not yet undergone formal peer review or publication, introduces significant scrutiny to the movement. While the study did not confirm microdosing as ineffective, it strongly suggests that expectation and the context of clinical trial participation contribute substantially to reported improvements in mood.
The results warrant a careful re-evaluation of the mechanisms driving purported benefits in psychedelic-adjacent treatments. The scientific community will need to analyze the full data set to understand the interaction between expectation, dosage, and clinical outcome measures like the MADRS.
For the emerging sector of psychedelic medicine, which seeks clinical validation for higher-dose therapies, these findings underscore the necessity of rigorous, placebo-controlled methodologies. Future research must clearly delineate the specific pharmacological action of these compounds from powerful psychological suggestion.
