Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials

  title={Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials},
  author={Meir Bialer and Emilio Perucca},
  pages={1082 - 1089}
Four pivotal randomized placebo‐controlled trials have demonstrated that adjunctive therapy with cannabidiol (CBD) improves seizure control in patients with Dravet syndrome (DS) and Lennox‐Gastaut syndrome (LGS). Between 47% and 68% of patients allocated to CBD treatment in these trials were receiving clobazam (CLB), which shows complex interactions with CBD resulting, in particular, in a 3.4‐ to 5‐fold increase in plasma concentration of the active metabolite norclobazam. This raises concern… 

Response: Cannabidiol antiseizure activity and its interactions with clobazam: “It’s déjà vu all over again” Yogi Berra

The data shown in the article provide ”the best clinical evidence to date that cannabidiol exerts therapeutic effects in patients with epilepsy that are independent of its interactions with clobazam,” even though effect size in the absence of clobzam comedication was modest.

Cannabidiol efficacy and clobazam coadministration: Where do we stand now?

The paradoxical increases in seizure frequency observed in a subset of CLBOff patients with Lennox-Gastaut syndrome attenuated the response in change in the seizure count analysis, without affecting or having little impact on the ≥50% responder rate.

The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond

Knowing knowledge of the pharmacokinetics, antiseizure efficacy and spectrum, and adverse effect profiles of currently used ASMs is an essential component of treating epilepsy successfully and maintaining a high quality of life for every patient, particularly those receiving polypharmacy for drug-resistant seizures.

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

The purpose of this review is to present data from the last few years on drug–drug interactions among of Aeds, as well as AEDs with other drugs, nutrients and food, and to pay a special attention to the new potential interactions of the applied first-generation AEDS.

Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials

To assess the efficacy and safety profile of add‐on cannabidiol (CBD) in patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) on clobazam and in the overall population of four

From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?

A considerable number of pre-clinical and clinical studies have provided strong evidence that phytocannabinoids has anticonvulsant properties, as well as being promising in the treatment of different neuropsychiatric disorders, such as depression, anxiety, post-traumatic stress disorder (PTSD), addiction, neurodegenerative disorders and autism spectrum disorder (ASD).

Cannabidiol efficacy independent of clobazam: Meta‐analysis of four randomized controlled trials

The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox‐Gastaut syndrome, and two

Cannabidiol drug interaction considerations for prescribers and pharmacists.

An overview of evidence-based pharmacokinetic predictions and general guidance about the dose range at which clinically relevant cannabidiol drug interactions are likely are likely is provided.



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.

Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Preliminary results from a recently completed controlled trial indicate that efficacy of CBD extends to the treatment of seizures associated with the tuberous sclerosis complex and to precipitation of some adverse effects, particularly somnolence.

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions

The present study aimed to address the nature of the interaction between CBD and clobazam to address speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobzam exposure.

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.

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.