Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program

@article{Gaston2019DrugdrugIW,
  title={Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program},
  author={Tyler E. Gaston and E. Martina Bebin and Gary R. Cutter and Steve B. Ampah and Yuliang Liu and Leslie P. Grayson and Jerzy P. Szaflarski},
  journal={Epilepsy \& Behavior},
  year={2019},
  volume={98},
  pages={201-206}
}
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Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials

The best clinical evidence to date is provided that CBD exerts therapeutic effects in patients with epilepsy that are independent of its interaction with CLB, and greater antiseizure effects, and a greater burden of adverse effects, are observed when CBD is combined withCLB.

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam

Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy

Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects

Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy.

Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.

The results show that the effect of cannabidiol on the median reduction in drop-seizure frequency in patients with Lennox-Gastaut syndrome may be explained by a drug-drug interaction with clobazam.

Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review

Cannabidiol has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol.

An update on drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors

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Carbonic anhydrase inhibitors have been in clinical use for decades for the management of various disorders but also for better controlling some diseases, such as hypoxic tumors, case for which the combination of CAIs with other anticancer agents proved to be synergistic.

Reduced efficacy and risk of seizure aggravation when cannabidiol is used without clobazam

Pharmacogenetic Predictors of Cannabidiol Response and Tolerability in Treatment‐Resistant Epilepsy

Pharmacogenetic variation is associated with CBD response and influences expression of CBD targets in TRE and Implicated pathways, including cholesterol metabolism and glutathione conjugation, demonstrate potential interactions between CBD and common medications that may require closer monitoring.

Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox–Gastaut Syndrome

The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies, and can provide preliminary support for additional research.

References

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Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome

This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial

Anticonvulsant effects of cannabinoids in mice: Drug interactions within cannabinoids and cannabinoid interactions with phenytoin

The administration of δ9-THC significantly potentiated the anticonvulsant effectiveness of phenytoin against electroshock seizures and this effect was further potentiated by the concurrent administration of CBD.

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial

Clobazam Therapeutic Drug Monitoring: A Comprehensive Review of the Literature With Proposals to Improve Future Studies

Future clobazam TDM studies need to use trough concentrations after steady state has been reached and standardization and more studies of C/D ratios from clobzam and other drugs can be helpful to move TDM forward.

Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome

Among children and adults with the Lennox–Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo.

Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy

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.

The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial