Abstract
The medical use of cannabis-derived products in children and adolescents has expanded beyond established indications for purified cannabidiol (CBD), with increasing investigation of CBD-rich extracts containing Δ9-tetrahydrocannabinol (THC) for neuropsychiatric conditions. Although preliminary studies suggest potential symptomatic benefits, the evidence remains limited by small samples, heterogeneous formulations, short follow-up, and insufficient assessment of long-term neurodevelopmental outcomes. Unlike CBD, THC directly activates CB1 receptors as a partial agonist, a pharmacological property underlying both its therapeutic and psychoactive effects. Following oral administration, THC undergoes extensive first-pass metabolism to the psychoactive metabolite 11-hydroxy-THC, with substantial interindividual variability in pharmacokinetics and pharmacodynamics supporting individualized dosing according to clinical response and tolerability. Experimental studies raise concerns regarding THC exposure during neurodevelopment, while observational studies associate frequent, high-potency recreational cannabis use with cognitive impairment, psychosis, and other adverse psychiatric outcomes. These findings cannot be directly extrapolated to regulated medicinal cannabinoid use, which differs substantially in product composition, dosing, administration, therapeutic indication, and clinical monitoring. Nevertheless, long-term neurodevelopmental safety data for medicinal THC exposure in children and adolescents remain limited. These uncertainties must be weighed against the consequences of inadequately treated disease, particularly severe drug-resistant epilepsy. Accordingly, the risk-benefit assessment of THC-containing products should be individualized, considering disease severity, treatment refractoriness, available evidence-based alternatives, therapeutic response, and tolerability. Long-term prospective studies and improved patient-selection strategies are needed to better define the role of THC-containing medicinal products in pediatric populations.
Authors
Crippa JAS, Hallak JEC