Landscape analysis of pre-registered clinical trials involving classical psychedelics

Psychedelic clinical trials have grown exponentially since 2006, with a sharp acceleration after 2019. Psilocybin is the most studied substance and closest to approval, while short-acting psychedelics like 5-MeO-DMT have recently entered trials with narrower clinical goals. Industry involvement is rising, but university-led research still dominates. Reporting of psychotherapy components increased after 2023 FDA recommendations, yet descriptions of interventions remain inconsistent. The rapid expansion across diverse indications and substances reflects growing clinical interest, though industry prioritizes scalability and approval. Incomplete reporting of psychotherapeutic elements limits cross-study comparisons and understanding of which therapeutic combinations optimize outcomes.

Study at a glance

Abstract

Psychedelic clinical research is expanding rapidly. This review analyses the state and trends in psychedelic clinical trial registrations. A systematic search of ClinicalTrials.Gov was conducted on 11 November 2024, to identify registered interventional trials investigating (therapeutic) effects of serotonergic psychedelics (e.g. lysergic acid diethylamide [LSD], psilocybin, [5-MeO-]DMT). Analyses included a negative binomial regression to assess time trends and descriptive summaries of study characteristics. Outcomes included registration trends, substance distribution, study phase progression, sample and trial characteristics, geographical distribution and psychotherapy reporting. A total of 241 trials were identified, with registrations rising exponentially after 2006 and an acceleration post-2019. Two-thirds of trials are ongoing or planned. Psilocybin remains the most frequently studied substance and is most advanced towards approval, but short-acting psychedelics ([5-MeO-]DMT) have recently been introduced with a more focused clinical scope. Industry involvement is increasing, though university-led research still dominates. Reports of psychotherapy components increased following 2023 FDA recommendations, though no major improvements in intervention descriptions were observed. The rapid expansion of registered psychedelic clinical trials with diverse indications and substances reflects growing clinical interest. While university-led studies initiated early investigations and established a broad knowledge base, later industry involvement increasingly prioritizes scalability and economic considerations by adopting a focused approach towards clinical approval. Inconsistent reporting of psychotherapeutic components limits cross-study comparability and complicates systematic investigations into which combinations of therapeutic elements (type, timing, intensity) may optimize clinical outcomes. Future efforts should focus on complete and standardized trial reporting at study registration to minimize bias, reduce interpretative ambiguity and facilitate cross-trial comparisons.