Methodology
Functional Unblinding: Why Psychedelic Trials Cannot Fully Blind
Participants in psilocybin trials correctly identify their arm far above chance because the experience is unmistakable, so expectancy inflates the drug arm and deflates placebo simultaneously — and no standard analysis separates the two. A meta-analysis restricted to equal-unblinding conditions found psychedelic therapy may be no more effective than open-label conventional antidepressants, and pre-treatment expectancy predicts outcome. The general test: could participants tell, and was the endpoint subjective?
The Biohacker Attribution Problem: Why 40-Item Protocols Reveal Nothing
When a protocol contains dozens of simultaneous interventions and reports improvement, no causal claim about any single intervention is recoverable — the kitchen-sink design destroys the very signal it claims to demonstrate.
The Clean Single-Lever Pattern: Why Simple Biological Mechanisms Disappoint in Trials
A mechanism is characterised, implicated in disease, and modulating it works in cells and animals — then the human trial underdelivers. The tell is step four: a mechanism statable in one clean sentence is likelier an incomplete model, because the single-sentence version is the one with the feedback loops removed. Instances include COX-2 selectivity, senolytics, and now 'boost neuroplasticity to offset neurodegeneration'. Redundancy, compensation, pleiotropy and endpoint substitution explain why the failures rhyme.
"The Topic Is Thin" Usually Means "The Noun Is Wrong"
A worked case of research failure: searches for a common plumbing technique returned almost nothing, suggesting an obscure regional practice. In fact one search named the wrong material entirely (felt instead of flax tow), another used the right term at too high an abstraction, and the rest was English reference sources not covering trade knowledge that German Wikipedia and trade literature document thoroughly. A heuristic for distinguishing a thin topic from a wrong search term.