From Adults to Adolescents: Bridging Scientific Potential and Evidence-Based Paths for Psychedelic-Assisted Interventions

Adolescent mental health conditions, especially treatment-resistant depression, pose a growing public health problem with high rates of illness, impairment, and suicide risk. Psychedelic-assisted therapies show strong antidepressant effects in controlled adult trials, but extending this work to adolescents is scientifically compelling yet ethically complex due to ongoing brain development and lack of pediatric data. This review examines the history of psychedelic use, summarizes adult findings on effectiveness and mechanisms, explores adolescent-specific opportunities and risks, and considers applications in co-occurring neurodevelopmental disorders. The authors do not advocate for premature clinical adoption but highlight translational gaps, developmental risks, and research priorities needed to responsibly assess these approaches in youth.

Study at a glance

Abstract

Adolescent mental health conditions, particularly treatment-resistant depression (TRD), represent a growing public health challenge associated with high morbidity, functional impairment, and elevated suicide risk. Psychedelic-assisted therapies have shown robust antidepressant and transdiagnostic effects in rigorously controlled adult trials. Extending this work to adolescents is scientifically compelling yet ethically complex, given neurodevelopmental vulnerabilities and the paucity of pediatric data. This review examines the historical context of psychedelic use, summarizes adult efficacy and mechanistic insights, explores adolescent-specific opportunities and risks, and considers applications in co-occurring neurodevelopmental disorders. Conventional treatments, including selective serotonin reuptake inhibitors and psychotherapy, are often inadequate for a narrow but substantial subset of clinical phenotypes, prompting interest in novel and rapid-acting interventions. Psychedelic-assisted therapies have shown promising results in adults with refractory mood disorders, yet their applicability to adolescents remains uncertain due to ongoing neurodevelopment and ethical constraints. This review critically examines evidence from adult psychedelic and psychedelic-adjacent interventions, including esketamine, and evaluates their potential relevance to adolescent populations through a developmental, mechanistic, and ethical lens. Rather than advocating for premature clinical adoption, we highlight translational gaps, developmental risks, and research priorities paramount to responsibly assess these approaches in youth.