Post-psychedelic and meditation-related challenges: a protocol for a mixed-methods longitudinal-observational study

Introduction: Psychedelics and meditation are increasingly used for therapeutic and wellness purposes. However, research into adverse effects (AEs) has been limited, without adequate investigation of the nature, clinical characteristics, and diversity of persisting challenges following psychedelic use and meditation practice. This study aims to better characterize the clinical and contextual features of these challenges, describe their longitudinal course, and compare psychedelic-related challenges to meditation-related challenges, selected as comparator conditions given previously characterized phenomenological and contextual overlap between the two. Methods and Analysis: This is a mixed-methods, enriched-sample, active-comparator (psychedelics vs. meditation) observational study comprising (1) a cross-sectional retrospective survey (N = 1,600), (2) a prospective 12-month longitudinal design involving six bimonthly surveys (n = 800), (3) 12 weeks of weekly ambulatory assessments combining quantitative symptom ratings with narrative voice report (n = 40), and (4) qualitative interviews (n = 60). Participants are recruited into two parallel arms of 800 each: individuals reporting psychedelic-related challenges and individuals reporting meditation-related challenges, defined as distress or impairment persisting after the acute effects of a psychedelic experience or period of meditation practice have subsided. Data collection includes a tailored item pool aimed at capturing the symptoms and phenomenology of these challenges in detail, developed from qualitative research and collaboratively with stakeholders with lived experience. The World Health Organization Disability Assessment Schedule (WHODAS 2.0) and measures of agent/exposure, set, setting, and social response are administered to characterize biopsychosocial correlates and functional impacts of AEs. Initial analyses will describe the phenomenology, course, and functional impact of psychedelic- and meditation-related challenges, and evaluate the structure and psychometric properties of the novel item pool. The study will produce a publicly available de-identified dataset supporting subsequent analyses, such as correspondence with recognized clinical syndromes, trajectory characterization, and cross-arm comparison of measurement structure, reported in registered reports or preregistrations.