Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?

Introduction

Mental disorders and substance misuse impose a vast global burden, with mental illness among the most costly and prevalent health problems in many high-income countries. Despite rising use of psychiatric medications and psychotherapies, population-level prevalence of mental illness has not declined and existing treatments often produce modest benefit, limited tolerability or restricted access. Carhart-Harris and colleagues situate psychedelic therapy—a psychologically supported administration of classic serotonergic psychedelics (agonists at the serotonin 2A receptor)—within this context, arguing it is a biopsychosocial intervention with promise for depression, end-of-life anxiety, addiction, OCD and possibly other conditions such as eating disorders and chronic pain. They note features that distinguish psychedelic therapy from conventional psychopharmacology: a novel mechanism, rapid and sometimes enduring effects after one or a few doses, low addiction potential, and a safety profile that centres on the need for careful psychological preparation and supervised contexts rather than toxicological hazard alone. Building on this background, the paper advocates supplementing traditional confirmatory double-blind randomised controlled trials (DB-RCTs) with more pragmatic research approaches, real-world data collection and digital technologies. The authors argue that pragmatic trials, basket protocols (single-protocol studies that test one intervention across multiple linked indications), electronic registries and smartphone-based outcome capture could accelerate learning about optimal dosing, psychotherapy integration, patient selection and safety across diverse populations. They position these approaches as complementary to DB-RCTs: useful early in the development pathway to avoid premature regulatory “lock-in” of suboptimal practice and to generate large datasets for prediction-of-response modelling, harm reduction and personalised care.