Microdosing

The most informative study to date is the self-blinding citizen science trial run out of Imperial College, which enrolled nearly two hundred people who were already microdosing and had them follow a randomisation procedure with their own supply, using opaque capsules and QR codes so that neither they nor the investigators knew which weeks were active.

Participants improved substantially on measures of mood, energy, creativity and wellbeing. So did the placebo weeks, by a statistically indistinguishable amount. The improvement was real; the drug was not what caused it.

A separate placebo-controlled laboratory trial found that low doses produced measurable physiological effects and some alteration in subjective state, but no reliable improvement in mood or cognitive performance relative to placebo.

A trial in people with major depression found no significant difference between repeated low doses and placebo on depression scores.

Large observational surveys consistently report that microdosers feel better than non-microdosers. Those studies recruit people who have chosen to microdose, know they are doing it, and are answering questions about a practice they have invested time and money in. Selection, expectancy and reporting bias all push the same direction.

That is not a reason to dismiss the reports. People are genuinely feeling better. It is a reason to be careful about attributing the improvement to the pharmacology rather than to the ritual of taking a deliberate action toward feeling better every few days.

Less than the confident tone of most microdosing content suggests. Nobody has run a long-term safety study.

The one specific concern with a plausible mechanism is cardiac valvulopathy. Chronic 5-HT2B receptor agonism causes fibrotic heart valve disease. This is established, and it is why fenfluramine and pergolide were withdrawn. Psilocin binds 5-HT2B. Occasional full doses are not a plausible risk; repeated low doses every few days for years are a genuinely unstudied exposure pattern, and it is the pattern that most resembles the drugs that caused the problem.

This has not been demonstrated to happen with psilocybin. It has also not been ruled out, and it is the reason to be more cautious about a years-long microdosing protocol than about a single session.