Evidence-Based Medicine is inadequate to develop evidence-based psychedelic therapies.

Between April and October 2024, expert bodies in the US and the Netherlands reached opposite conclusions on MDMA for PTSD. The FDA rejected Lykos Therapeutics' New Drug Application despite prior breakthrough therapy status, while the Dutch State Commission recommended making the treatment available as soon as possible. These contrasting decisions highlight epistemic differences in evidence assessment: the FDA's approach aligned with traditional Evidence-Based Medicine (EBM), whereas the Dutch approach resembled the newer EBM+ framework. Drawing on historical fatal examples and recent evidence-assessment debates (e.g., masking during COVID-19), the authors argue that shifting to EBM+ is essential for reliable assessments of psychedelic therapies.

Study at a glance

Abstract

Between April and October 2024, expert bodies in two countries reached strikingly opposite conclusions about the therapeutic use of 3,4-methylenedioxymethamphetamine (MDMA). On the one hand, the Food and Drug Administration in the USA rejected a formal New Drug Application from a specific drug sponsor, Lykos Therapeutics, for Post-Traumatic Stress Disorder (PTSD). The decision was surprising to many, given the FDA granting it “breakthrough therapy status” a few years before. Across the Atlantic, the Dutch State Commission on MDMA recommended the same treatment to be made available as soon as possible for PTSD and also investigated for other conditions. Apart from important differences regarding the legal mandate of these two expert bodies, some important epistemic differences are notable in these two distinct approaches to assess the evidence. These cases serve as examples of the current challenges to develop and implement evidence-based psychedelic therapies given the limitations of the prevailing influential framework of Evidence-Based Medicine (EBM), which seems to have particularly influenced the FDA’s decision. On the other hand, the Dutch approach more closely resembles the recent EBM+ approach. Drawing from historically tragic fatal examples, as well as recent advances in evidence assessment, such as masking and mask mandates during the COVID-19 pandemic, it is argued that a shift to EBM+ is paramount to allow reliable assessments towards evidence-based implementation of psychedelics as therapeutic tools.