Cannabidiol Lacks Direct Effect on Cortical Excitability: A Randomized, Double Blind, Placebo Controlled, 3‐Way Crossover Trial
Clinical Pharmacology & Therapeutics, vol. 119, pp. 147–157
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.
Authors 8
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Andriy A. Gorbenko Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Leiden University · Leiden University Medical Center · Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Leiden University Medical Centre Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
Leiden University Medical Centre, Leiden, The Netherlands
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Catherine M.K.E. de Cuba Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Leiden University · Leiden University Medical Center · Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Leiden University Medical Centre Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
Leiden University Medical Centre, Leiden, The Netherlands
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Annika A. de Goede Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
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Titiaan E. Post Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
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Román Bohoslavsky Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
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Pamela K. Strugala Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
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Jules A. A. C. Heuberger Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
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Geert Jan Groeneveld corresponding Aachen Centre for Human Drug Research Leiden the Netherlands Centre for Human Drug Research (CHDR)
Leiden University · Leiden University Medical Center · Centre for Human Drug Research
Affiliation as printed
Centre for Human Drug Research Leiden The Netherlands
Leiden University Medical Centre Leiden The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands
Leiden University Medical Centre, Leiden, The Netherlands
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