The renaissance of research on psychedelics in child and adolescent psychopharmacology

The recent approval of esketamine for adults has renewed interest in psychedelic compounds for psychiatric use, but their relevance for children and adolescents is unclear. This review examines the rationale for investigating classic serotonergic psychedelics (e.g., psilocybin, LSD), the entactogen MDMA, and dissociative compounds like ketamine and esketamine in young populations. Ongoing and planned trials primarily involve adolescents aged 16 years and older, driven by unmet needs in child and adolescent psychiatry, where few medications are approved and therapeutic response is often unsatisfactory. Potential targets include anorexia nervosa, autism spectrum disorder symptoms, obsessive-compulsive disorder, resistant depression, and severe PTSD. Translation to pediatric populations requires caution due to developmental vulnerabilities and limited long-term safety data.

Study at a glance

Abstract

Aims The recent regulatory approval of esketamine in adults heralded the renaissance of research into psychedelic compounds. However, the relevance of this resurgence for children and adolescents remains unclear. This review examines the rationale for investigating psychedelics in pediatric psychopharmacology. Methods We reviewed recent literature, regulatory documents, and clinical trial registries addressing the psychiatric use of classic serotonergic psychedelics (e.g., psilocybin, LSD), the entactogen MDMA, and dissociative compounds such as ketamine and esketamine in adolescent and young populations. Although ketamine is not a classic serotonergic psychedelic, it represents a paradigm for innovative pharmacological approaches. Results Ongoing and planned trials primarily involve adolescents aged 16 years and older. Interest in these compounds is driven by significant unmet needs in child and adolescent psychiatry, where few medications are approved, and unsatisfactory therapeutic response is common. Potential targets include anorexia nervosa, core symptoms of autism spectrum disorders, obsessive-compulsive disorder, resistant depression, and severe PTSD. The fact that psychedelics may have long-lasting effects after only a few sessions raises the question of their effects on neuroplasticity. Conclusions Although psychedelic research has entered a new phase in adult psychiatry, translation to pediatric populations requires caution due to developmental vulnerabilities and limited long-term safety data. Rigorous clinical trials, ethical safeguards, and regulatory oversight are essential before broader application in children and adolescents can be considered.