Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions
@article{Anderson2019CoadministeredCA, title={Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions}, author={Lyndsey L. Anderson and Nathan L. Absalom and Sarah V. Abelev and Ivan K Low and Peter T. Doohan and Lewis J Martin and Mary Chebib and Iain S. McGregor and Jonathon C Arnold}, journal={Epilepsia}, year={2019}, volume={60}, pages={2224 - 2234} }
Cannabidiol (CBD) has been approved by the US Food and Drug Administration (FDA) to treat intractable childhood epilepsies, such as Dravet syndrome and Lennox‐Gastaut syndrome. However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first‐line medication, clobazam. This recognized interaction has led to speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobazam exposure. The present…
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Commentary on: Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions
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The authors properly indicate that an increased risk for sudden unexpected death is observed in patients with Dravet syndrome; therefore the aim of their experimental study to evaluate the effectiveness of the combined treatment of cannabidiol with clobazam is fully justified.
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References
SHOWING 1-10 OF 50 REFERENCES
Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy
- Medicine, PsychologyEpilepsia
- 2015
Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children, and it is predicted a drug–drug interaction.
Interactions between cannabidiol and commonly used antiepileptic drugs
- Biology, MedicineEpilepsia
- 2017
To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open‐label safety…
Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes
- Medicine, BiologyThe Annals of pharmacotherapy
- 2019
CBD offers patients with DS and LGS a new treatment option for refractory seizures and is well tolerated, the first cannabis-derived medication with approval from the US Food and Drug Administration.
The pharmacokinetics and the pharmacodynamics of cannabinoids.
- Medicine, BiologyBritish journal of clinical pharmacology
- 2018
The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects.
Clobazam and Its Active Metabolite N-desmethylclobazam Display Significantly Greater Affinities for α2- versus α1-GABAA–Receptor Complexes
- Biology, ChemistryPloS one
- 2014
GABAA-receptor binding affinities of CLB, N-desmethylclobazam (N-CLB), CLN, and ZOL were characterized with native receptors from rat-brain homogenates and on cloned receptors from HEK293 cells transfected with combinations of α (α1, α2, α3, or α5), β2, and γ2 subtypes, demonstrating the high preference for α1 receptors.
Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
- Medicine, PsychologyJournal of epilepsy research
- 2017
There is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes, for the first time, according to currently available information.
Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome
- MedicineNeurology
- 2018
This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.
Benzodiazepine pharmacology and central nervous system-mediated effects.
- Medicine, BiologyThe Ochsner journal
- 2013
For any patient taking a BZD, the prescribing physician must carefully evaluate the risks and benefits, and higher-risk patients require careful considerations, as Clinically appropriate use of BZDs requires prudence and the understanding of pharmacology.
Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome
- Biology, PsychologyProceedings of the National Academy of Sciences
- 2017
CBD effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome, a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1.