The Use of Psychedelics in the Treatment of Adult ADHD: A Systematic and Mechanistic Review.

Abstract

Interest in classical psychedelics as potential treatments for ADHD has grown alongside broader psychiatric psychedelic research, but ADHD-specific evidence remains limited. This systematic review examined prospective and experimental studies on whether classical psychedelics, including microdosing-like use and retreat-based exposure, are associated with changes in adult ADHD symptoms and related functioning. A PRISMA-guided systematic review was conducted using a PECO/PICO framework focused on adults (≥18 years) with diagnosed ADHD and/or elevated ADHD symptomatology who were exposed to a classical psychedelic and assessed prospectively with quantitative ADHD outcomes. Major databases were searched, with reference screening and targeted checks for recent or registered trials. Risk of bias was assessed using RoB 2 for the RCT and ROBINS-I for non-randomized studies. Because of heterogeneity and the small number of studies, findings were synthesized narratively. Five studies met the inclusion criteria. Five prospective/experimental studies were included: three naturalistic online microdosing cohorts, one randomized double-blind placebo-controlled phase 2A trial of low-dose LSD, and one pre-post ayahuasca retreat pilot. In uncontrolled naturalistic microdosing studies, participants reported short-term reductions in ADHD symptom ratings together with improvements in well-being and affect-related functioning; however, these studies were highly vulnerable to self-selection, expectancy, attrition, and non-standardized exposure. In contrast, the only randomized placebo-controlled ADHD trial found improvement in both LSD and placebo groups, with no statistically significant advantage for LSD on clinician-rated or self-reported ADHD outcomes. Objective cognitive findings were limited and inconsistent, and safety data outside the supervised trial context were sparse. Naturalistic studies provide, at most, low-certainty signals of perceived short-term improvement, but the strongest controlled evidence does not demonstrate drug-specific efficacy of repeated low-dose LSD for core ADHD symptoms. Current evidence therefore does not allow separation of pharmacological effects from expectancy, setting, self-monitoring, and broader experiential/contextual influences, and is insufficient to support psychedelics as an evidence-based treatment for ADHD.

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