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

@article{Bergmann2019ClinicalTS,
  title={Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.},
  author={Kirsten Riber Bergmann and Karen Broekhuizen and Geert Jan Groeneveld},
  journal={British journal of clinical pharmacology},
  year={2019}
}
With this study we aim to test the hypothesis that the effect of cannabidiol on drop-seizure frequency in patients with Lennox-Gastaut syndrome and Dravet syndrome could be attributed to a drug-drug interaction with clobazam. We performed clinical trial simulations for the effect of 20 mg/kg/day cannabidiol on drop-seizure frequency in patients with Lennox-Gastaut syndrome. We assumed that patients taking 10 or 20 mg clobazam would have a 2- to 7-fold increase in N-desmethylclobazam exposure… 
View on PubMed
europepmc.org
11 Citations
Background Citations
2
Methods Citations
1
Results Citations
2

Figures and Tables from this paper

11 Citations

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.

Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research

Interaction of cannabidiol with other antiseizure medications: A narrative review

Parasitic pharmacology: A plausible mechanism of action for cannabidiol

Two randomised placebo‐ controlled and appropriately powered studies were performed with CBD in patients with Lennox–Gastaut syndrome and severe myoclonic epilepsy of infancy, which led to the FDA approval of Epidiolex (CBD) for the treatment of seizures associated with these rare and severely disabling epilepsy syndromes.

The Search for New Anticonvulsants in a Group of (2,5-Dioxopyrrolidin-1-yl)(phenyl)Acetamides with Hybrid Structure—Synthesis and In Vivo/In Vitro Studies

The studies showed that the most plausible mechanism of action of compound 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels, which revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of cytochrome P450, compared to reference compounds.

Cannabidiol in epilepsy: The indications and beyond

  • M. Ryan
  • Medicine, Psychology
    The mental health clinician
  • 2020
This article examines 3 cases: 1 of a patient with Lennox-Gastaut syndrome, 1 of off-label use of cannabidiol to treat epilepsy, and 1 of nonprescription forms of cannABidiolto treat epilepsy.

Over the counter low-dose cannabidiol: A viewpoint from the ACRE Capacity Building Group

Some considerations in relation to over-the-counter availability of CBD and opportunities to improve knowledge about its potential therapeutic benefits alongside its increased uptake are proposed.

The Essential Medicinal Chemistry of Cannabidiol (CBD).

This Miniperspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labelled health products, and associated…

Cannabidiol efficacy and clobazam status: A systematic review and meta‐analysis

To evaluate the potential impact of concomitant clobazam (CLB) use on the efficacy of cannabidiol (CBD) treatment in patients with Dravet syndrome and Lennox‐Gastaut syndrome using meta‐analytical…

The ‘entourage effect’ or ‘hodge-podge hashish’: the questionable rebranding, marketing, and expectations of cannabis polypharmacy

  • P. Cogan
  • Medicine
    Expert review of clinical pharmacology
  • 2020
A broad definition of the entourage effect is presented, followed by brief summaries of the nature of cannabis polypharmacy and the commonly cited contributing phytochemicals, with special attention to their attendant adverse effects.

References

SHOWING 1-10 OF 27 REFERENCES

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.

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

The pharmacokinetics and the pharmacodynamics of cannabinoids.

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.

Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children

The simulations show that DDIs can cause major changes in AED concentrations both in adults and children, and suggest that currently recommended dosing algorithms and titration procedures do not ensure attainment of appropriate therapeutic concentrations.

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.

Plant-Derived and Endogenous Cannabinoids in Epilepsy

There is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy, based on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner.

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.

Gaps in predicting clinical doses for cannabinoids therapy: Overview of issues for pharmacokinetics and pharmacodynamics modelling

Review of currently available PK and/or PD models of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) to highlight the major issues for modelling this complex therapeutic area.

A Phase 1, Open‐Label, Pharmacokinetic Trial to Investigate Possible Drug‐Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects

Cannabidiol was moderately well tolerated, with similar incidences of adverse events reported when coadministered with clobazam, stiripentol, or valproate, and when co Administered with each antiepileptic drug.

Drug‐metabolism mechanism: Knowledge–based population pharmacokinetic approach for characterizing clobazam drug‐drug interactions

Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobzam PK in this study, dosage adjustments may not be required forClobazem in the presence of the AEDS investigated here.