Long-term plasma monitoring of THC and CBD in pediatric drug-resistant epilepsy: Implications for cannabidiol therapy with Epidyolex®
Alessia Cafaro 1, Antonella Riva 2, Federica Pigliasco 1, Sebastiano Barco 1, Valentina Manca 2, Maria Stella Vari 3, Maria Margherita Mancardi 4, Lino Nobili 2 4, Simona Pichini 5, Francesco Paolo Busardò 6, Pasquale Striano 2 3, Giuliana Cangemi 1
- 1Biochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis, IRCCS Istituto Giannina, Gaslini, Genoa, Italy.
- 2Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
- 3Paediatric Neurology and Muscular Disease Unit, IRCCS Istituto Giannina Gaslini, full member of ERN EpiCARE, Genoa, Italy.
- 4Unit of Child Neuropsychiatry, IRCCS Gaslini, Genoa, Italy.
- 5National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy.
- 6Department of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Affiliationer
This study evaluated long-term plasma concentrations of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in children receiving highly purified cannabidiol (hpCBD; Epidyolex®) therapy for drug-resistant epilepsy. A retrospective analysis was performed on 38 patients with a median age of 11 years (IQR, 5) treated in a single center from 2019 to 2024. Incremental doses of Epidyolex® (mean dose: 13.6 mg/kg/day) were administered, and plasma levels of CBD and THC were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). THC remained consistently undetectable (<0.2 μg/L) at all time points, confirming the negligible systemic exposure. CBD levels increased dose-dependently, reaching a median concentration of 89.8 μg/L (IQR, 112.2) at final follow-up, demonstrating a significant positive correlation (p < 0.0001) between dosage and plasma concentration. Epidyolex® treatment effectively maintains therapeutic CBD levels without detectable THC, supporting the safety and suitability of this therapy. These results highlight the value of plasma CBD monitoring to verify dose-dependent exposure and support safe, individualized treatment with CBD. PLAIN LANGUAGE SUMMARY: This study examined blood levels of cannabidiol (CBD) and tetrahydrocannabinol (THC) in children with drug-resistant epilepsy treated with highly purified CBD (Epidyolex). CBD levels increased proportionally with the dose, while THC levels remained undetectable. The consistent lack of THC detection across all measured time points and dose levels suggests that systemic exposure to THC remains negligible, even with prolonged administration.
