Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy

  title={Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy},
  author={James W. Wheless and Dennis J. Dlugos and Ian Miller and D. Alexander Oh and Neha Parikh and Steven Phillips and J. Ben Renfroe and Colin M. Roberts and Isra Saeed and Steven Sparagana and Jin Yu and Maria Roberta Cilio},
  journal={CNS Drugs},
  pages={593 - 604}
AbstractBackgroundPrior studies have evaluated the use of various constituents of cannabis for their anti-seizure effects. Specifically, cannabidiol, a non-psychoactive component of cannabis, has been investigated for treatment-resistant epilepsy, but more information is needed particularly on its use in a pediatric population.ObjectiveThe objective of this study was to evaluate the pharmacokinetics and safety of a synthetic pharmaceutical-grade cannabidiol oral solution in pediatric patients… 

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

Efficacy and tolerance in the study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD, which might be a reasonable alternative to plant derived cannabidiol.

Clinical pharmacology of cannabidiol in refractory epilepsy.

A systematic and updated review of the pharmacology of cannabidiol in the context of refractory epilepsy, with special emphasis on its pharmacokinetics, adverse drug reactions and drug-drug interactions, finds the strongest evidence is provided with clobazam.

Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy

Most of the authors' patients showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system, encouraging the use of CBD therapeutic drug monitoring.

A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers

This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products.

Cannabidiol in the Treatment of Epilepsy

The aim of this article is to thoroughly review available research data and practical recommendations to provide the treating physician with the necessary information for counseling patients with epilepsy.

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.

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.

Cannabidiol in Pharmacoresistant Epilepsy: Clinical Pharmacokinetic Data From an Expanded Access Program

These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting and the most relevant finding was the higher CBD C/D in adults.



Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US

Over a 4-year period, cannabidiol was effective in 26.9% of children with otherwise refractory epilepsy and was well tolerated in about 20% of patients, but 80.8% had adverse events, including 23.1% with serious adverse events.

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.

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.

Trial of Cannabidiol for Drug‐Resistant Seizures in the Dravet Syndrome

Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive‐seizure frequency than placebo and was associated with higher rates of adverse events.

Cannabis for the Treatment of Epilepsy: an Update

Understanding of CBD’s efficacy and safety in the treatment of TRE has expanded significantly in the last few years, and data from both open-label expanded access programs (EAPs) and randomized placebo-controlled trials (RCTs) of a highly purified oral preparation of CBD are presented.

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

In vivo and in vitro reports of CBD administration across a wide range of concentrations suggest controlled CBD may be safe in humans and animals, but further studies are needed to clarify reported in vitro and in vivo side effects.