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. 2025 Aug 20.
doi: 10.1002/cpt.70038. Online ahead of print.

Cannabidiol Lacks Direct Effect on Cortical Excitability: A Randomized, Double Blind, Placebo Controlled, 3-Way Crossover Trial

Andriy A Gorbenko  1   2 , Catherine M K E de Cuba  1   2 , Annika A de Goede  1 , Titiaan E Post  1 , Roman Bohoslavsky  1 , Pamela K Strugala  1 , Jules A A C Heuberger  1 , Geert Jan Groeneveld  1   2
Affiliations

Cannabidiol Lacks Direct Effect on Cortical Excitability: A Randomized, Double Blind, Placebo Controlled, 3-Way Crossover Trial

Andriy A Gorbenko et al. Clin Pharmacol Ther. .

Abstract

Cannabidiol (CBD) is approved as an adjunctive treatment of seizures associated with Dravet syndrome, Lennox-Gastaut Syndrome, and tuberous sclerosis. Its therapeutic and adverse effects are thought to arise, at least partly, from a pharmacokinetic interaction with clobazam, another anti-seizure medication (ASM). The goal of this study was to evaluate the intrinsic anti-epileptic and sedative properties of CBD. A randomized, double-blind, placebo-controlled, 3-way crossover trial was conducted in 25 healthy males. On each visit, single doses of 30 mg CBD, 700 mg CBD, or placebo were administered orally. The effects of CBD on cortical excitability were measured using transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG). Sedative properties were assessed using a validated CNS test battery. Pharmacokinetic sampling was performed. Data were analyzed using a mixed-effects model. CBD did not have significant effects on single pulse and paired pulse TMS-EMG parameters, compared to placebo. Some significant clusters were seen on paired pulse TMS-EEG at 3 hours post-dose for 30 mg CBD, and at 3 and 5 hours post-dose for 700 mg CBD. CBD did not have significant effects on any tests assessing its sedative properties. These results suggest that CBD may lack intrinsic anti-epileptic and sedative properties and that its effects could be primarily a product of interactions with other drugs, notably clobazam.

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References

    1. Talwar, A., Estes, E., Aparasu, R. & Reddy, D.S. Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: a systematic review and meta‐analysis. Exp. Neurol. 359, 114238 (2023).
    1. Geppert, J., Lietzow, J., Hessel‐Pras, S., Kirsch, F., Schäfer, B. & Sachse, B. Usage and health perception of cannabidiol‐containing products among the population in Germany: a descriptive study conducted in 2020 and 2021. BMC Public Health 23, 2318 (2023).
    1. Bilbao, A. & Spanagel, R. Medical cannabinoids: a pharmacology‐based systematic review and meta‐analysis for all relevant medical indications. BMC Med. 20, 259 (2022).
    1. Drug Approval Package: Epidiolex (Cannabidiol) <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210365Orig1s000T.... Accessed March 3, 2025.
    1. FDA. FDA Approves New Indication for Drug Containing an Active Ingredient Derived from Cannabis to Treat Seizures in Rare Genetic Disease | FDA <https://www.fda.gov/news‐events/press‐announcements/fda‐approves‐new‐ind... Accessed March 3, 2025.

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