In psychedelic studies, participants almost always know whether they got the real drug or a placebo because the experience is so powerful and obvious. This is called 'functional unblinding,' and it makes it hard to know if the benefits come from the drug or from people simply expecting to feel better. Regulators and scientists are increasingly calling this out as a problem that no one has solved yet.
No current trial design eliminates expectancy effects from psychoactive blinding failure, and this critique was central to the 2024 FDA advisory rejection; it will continue to appear in regulatory and scientific discussion.