In this episode of Research Notes, I talk with Dr. Gabe Loewinger of the National Institute of Mental Health about a core challenge in psychedelic clinical trials: participants often know whether they received the treatment. This “functional unblinding” means that people in different trial arms can develop very different expectations about what the treatment will do, and those expectations may themselves influence outcomes.

We explore why common approaches—like adjusting for what participants believe or expect—can actually make things worse from a causal inference perspective. Expectancy is not just a nuisance variable to control for; it sits on the pathway between treatment and outcome. Instead, we discuss an alternative framework based on estimating controlled direct effects, which aims to put treatments on a more equal footing by explicitly accounting for how expectations operate. Along the way, we use causal diagrams and thought experiments to clarify why this is such a difficult problem.