The regulatory action acknowledges the drug’s medical use and clears the way for it to be marketed.
Neurology Reviews. 2018 November;26(11):29
WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.
The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.
A Low Potential for Abuse
“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.
During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.
All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.
An Established Medical Use
Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.
Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.
In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.
Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.
Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.