Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a depressive episode, 12.5% reporting serious thoughts of suicide, and 17% meeting criteria for a substance use disorder.1 Close to 5% of adolescents experience posttraumatic stress disorder.2 Impairing psychiatric symptoms remain present in upwards of 40% of adolescents after receiving existing mental health services,3 so it is necessary to identify additional and more effective treatment options. We propose there is an acceptable benefit-to-risk calculation that supports trialing classic serotonergic psychedelics (eg, psilocybin) and phenethylamine compounds with empathogenic and entactogenic range of effects (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in combination with psychotherapy among select adolescents aged 16 to 17 years. Specifically, we propose testing these treatments among adolescents aged 16 to 17 years who are experiencing treatment-resistant manifestations of psychiatric disorders (ie, multiple failed trials of current evidence-based treatments) or psychiatric disorders that are in line with the current evidence base for adults as determined, for example, by the breakthrough designation of the US Food and Drug Administration for a particular psychedelic medicine (eg, psilocybin for major depressive disorder, MDMA for posttraumatic stress disorder).
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