Psychedelics in functional disorders: A scoping review

Functional disorders, characterised by symptoms unexplained by organic disease, impose a significant burden on individuals and healthcare systems. Existing treatments are limited in efficacy, with no effective pharmacotherapies. There is growing evidence supporting the treatment potential of psychedelics in neuropsychiatric conditions, including several distinct functional disorders. This scoping review explores existing studies using classic psychedelics in functional disorders to identify current knowledge, highlight evidence gaps, and inform future research. Four databases (MEDLINE, PsychINFO, EMBASE, and Web of Science) and the World Health Organisation International Clinical Trials Registry Platform were searched, supplemented by citation searching, relevant websites, and search engine alerts. 62 reports were identified from 55 unique studies, comprising six surveys, six case studies of naturalistic psychedelics use, 33 completed clinical studies, and 10 registered trials. For completed studies, most refer to data from prior to 1976, few used comparator or control groups, and LSD was the most common psychedelic used. For registered trials planned or currently underway, most use comparator or control groups and all use psilocybin. Functional neurological symptoms represented the most common category of functional disorder studied. 60.7% demonstrated improvement. Adverse events encompassed several acute psychological and physical effects, including transient exacerbations of functional symptoms. Despite showing potential as a novel treatment, the evidence is limited by predominantly observational study designs, disparate methodologies, and a lack of long-term outcomes. Future research must adapt to the evolving complexities of trial designs in psychedelic research, implement standardised treatment protocols, explore mechanistic analyses, and incorporate comprehensive outcome and safety assessments. • Psychedelics demonstrate an encouraging safety profile and signals of efficacy. • Higher improvement rates were linked to higher doses and therapeutic intent. • However, the evidence is limited by outdated research methods, predominantly observational study designs, and heterogeneity in methodology and outcome reporting. • Further high-quality research is required including standardised treatment protocols, control groups, mechanistic analyses, and comprehensive outcomes and safety assessments.