“Self-Blinding Citizen Science to Explore Psychedelic Microdosing”, Balázs Szigeti, Laura Kartner, Allan Blemings, Fernando Rosas, Amanda Feilding, David J. Nutt, Robin Carhart-Harris, David Erritzoe2021-03-02 (, , ; backlinks; similar)⁠:

[commentary] Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect.

This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date.

All psychological outcomes improved statistically-significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no statistically-significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but statistically-significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind.

The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Figure 4: Each panel shows the adjusted mean estimate of the change from baseline and the 95% CI for the accumulative outcomes. Top horizontal bars represent the over time comparisons for each group (from baseline to post-regime [week 5] and from baseline to follow-up). Symbols on top of bars show the statistical-significance for the PL [4 weeks placebo]/HH [2 weeks placebo, 2 weeks microdose]/MD [4 weeks microdose] groups, respectively (eg. change from baseline to post-regime in well-being was statistically-significant for the MD group, but not statistically-significant for the other two groups, see legend). There was no statistically-significant between-groups difference at any timepoint for any scale. Sample size was 240/191/159 at the pre-test, post-regime and 4 weeks follow-up timepoints, respectively. See Supplementary files 4, 5, and 6 for the unadjusted descriptive statistics, adjusted mean differences (and their statistical-significance) associated with both over time and between group comparisons and model parameters, respectively.

…It is worth noting that the current study was designed to protect blinding integrity by including placebos for the microdose group as well, administering the microdose capsules on different days of the week and by including the half-half group. The 3-arm design can be seen as a strength in this regard, adding ambiguity and thus strengthening blinding. Illustrative of the integrity of the blind, we received several emails from participants in the PL group who were in disbelief after opening their unused envelopes containing unused capsules after the conclusion of the study:

eLife digest: Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of ‘magic mushrooms’), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, ‘microdosing’—a way of administering psychedelics that involves taking about 10% of a recreational dose 2 or 3× per week—has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy.

A key feature of modern medicine are ‘placebo control’ studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether they are taking drug or placebo. This control ensures that observed effects are due to the drug itself and not to unrelated psychological causes. For example, in trials of mood medicines, participants often expect to feel happier, which in itself improves their mood even when taking a placebo. This is known as the placebo effect.

Restrictive drug policies make placebo-controlled studies on psychedelics difficult and expensive, in particular for microdosing, which involves taking psychedelics over a longer time period. To overcome this problem, Szigeti et al 2021 developed a new citizen-science approach, where microdosers implemented their own placebo control based on online instructions. The advantages are the low cost and the ability to recruit participants globally. The experiment was completed by 191 microdosers, making it the largest placebo-controlled study on psychedelics to-date, for a fraction of the cost of an equivalent clinical study.

The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing statistically-significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also improved: there were no statistically-significant differences between the two groups. The findings confirmed positive anecdotes about microdosing improving people’s moods, but at the same time show that taking empty capsules, knowing they might be microdoses, have the same benefits. This result suggests that the observed benefits are not caused by the microdose, but rather by psychological expectations.

The study’s innovative ‘do-it-yourself’ approach to placebo control may serve as a template for future citizen science studies on other popular phenomena where positive expectations and social factors could play a role, such as cannabidiol (CBD) oils, nootropics and nutrition.