Clinical implications of trials investigating drug‐drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

  title={Clinical implications of trials investigating drug‐drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs},
  author={Philip N Patsalos and Jerzy P. Szaflarski and Barry E. Gidal and Kevan E. VanLandingham and David J.P. Critchley and Gilmour Morrison},
  pages={1854 - 1868}
Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox‐Gastaut syndrome or Dravet syndrome in randomized, double‐blind, add‐on, controlled phase 3 trials. It is important to consider the possibility of drug‐drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes… 

Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy

Current research suggests that cannabis exhibits the potential to induce DDI under certain circumstances and there is a strong potential for cannabis-induced DDI among major drug-metabolizing enzymes.

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.

The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations

Clinicians should discuss THC and CBD use in youth prescribed SSRIs and be aware of the impact of initiating, stopping, or decreasing cannabinoid use as this may significantly affect es/citalopram and sertraline exposure.

Not your usual drug‐drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications

Prescribers who treat patients with epilepsy should be familiar with mAb pharmacology to better anticipate potential mAb‐ASM interactions and avoid toxicity, loss of seizure control, or impaired efficacy of mAb treatment.

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19 †

Advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19 are presented.

Inhibition of UDP-Glucuronosyltransferase Enzymes by Major Cannabinoids and Their Metabolites

This study is the first to show the potential of cannabinoids and their metabolites to inhibit all the major kidney UGTs as well as the two most abundant U GTs present in liver, and suggests that greater drug-drug interaction effects might be observed from co-use of cannabinods and therapeutics that are cleared renally.

Cannabinoids in the Treatment of Epilepsy: A Review

This review seeks to offer a fairly comprehensive description of the facets of cannabinoid therapy for refractory epilepsy and examines the interactions between cannabinoids and other conventional antiseizure medications.

Cannabidiol in canine epilepsy.

Time to onset of cannabidiol (CBD) treatment effect in Lennox–Gastaut syndrome: Analysis from two randomized controlled trials

To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), post hoc analyses of data from two randomized, placebo‐controlled, Phase 3 trials of patients with Lennox–Gastaut syndrome were conducted.



A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam

The safety profile of GW Pharmaceuticals’ CBD formulation with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate; one serious AE (seizure cluster) led to CBD discontinuation.

Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.

  • G. ZaccaraE. Perucca
  • Biology, Medicine
    Epileptic disorders : international epilepsy journal with videotape
  • 2014
These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects,such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of sodium channel blocking antiepileptic drugs.

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.

Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from two clinical trials

Co-administration of CYP3A4/CYP2C19 inhibitors will likely increase exposure to selumetinib, while CYP 3A4 inducers will likely reduce its exposure.

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

Current knowledge on the pharmacokinetics and metabolic fate of CBD in humans is summarized, studies on the biological activity of CBD metabolites either in vitro or in vivo are reviewed, and relevant drug–drug interactions are discussed.

Cytochrome P450 Structure, Function and Clinical Significance: A Review.

This review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, pharmacoepigenetics and clinical significance that may be used by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products.

Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19.

Results indicate that CBD caused potent CYP2C19 inhibition, in which one free phenolic hydroxyl group and the pentyl side chain of CBD may play important roles.

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.

A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug–Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy

Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy, and safety results were consistent with the known safety profile of cannABidiol at a dose of 20 mg/kg/day.