Pharmacological and Therapeutic Properties of CBD for Epilepsy

Authors : Franco V , Perucca  
DOI : 10.1007 / s40265-019-01171-4S

What is CBD ? 

Cannabidiol ( CBD ) is a major active component of the Cannabis plant (Hemp ) , which, unlike tetrahydrocannabinol ( THC ), lacks excitement-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD – enriched products for the treatment of Epilepsy.

 

Approval : 

In 2018, an Oil-based highly purified liquid formulation of cannabidiol ( Epidiolex ) derived from Cannabis Sativa ( Hemp )

was approved by the FDA for the treatment of seizures associated with Dravet syndrome ( DS ) and Lennox – Gastaut syndrome ( LGS ).

 

Mechanism : 

It’s not clear how CBD controls seizures but it may involve the Antagonistic effect of ( GPR55) and desensitization of (TRPV1) pathways including inhibition of Adenosine uptake.

 

CBD has complex physiological effects with a prominent first-pass ()effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat / high-calorie meal.

Trials : 

In four randomized, double-blind, parallel-group, adjunctive – therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS.

 

Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex.

 

Side Effects : 

The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances.

 

Results : 

About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients, a CBD – induced increase in serum levels of the active metabolite Norclobazam have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.