Microdosing

The largest placebo-controlled study to date is the self-blinding citizen science trial run out of Imperial College. 191 people who were already microdosing (LSD or psilocybin) completed it, following a randomisation procedure with their own supply, using opaque capsules and QR codes so that they did not know which weeks were active.

Psychological outcomes such as wellbeing improved over the four weeks in the microdose group. So did they in the placebo group, with no significant difference between the two. A few acute measures (mood, energy, creativity) showed small differences, which the authors attribute to people guessing correctly what they had taken. Their conclusion: the anecdotal benefits can be explained by the placebo effect.

A separate double-blind study gave 34 people starting to microdose either 0.5 g of dried cubensis or placebo. The active dose produced noticeable subjective effects (in those who correctly guessed their condition) and measurable EEG changes, but no evidence of improved wellbeing, creativity or cognition, and a few small changes in the direction of cognitive impairment.

A preregistered placebo-controlled crossover study found three weeks of psilocybin microdosing did not change emotion processing or symptoms of anxiety and depression compared with placebo. Trials in people with diagnosed depression are only now under way.

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 This is established, and it is why fenfluramine and pergolide were withdrawn.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.