DEA and FDA clear Epidiolex: Where do we go from here?

On September 27, 2018, the Drug Enforcement Agency (DEA) made a remarkable move. The agency placed a cannabidiol (CBD) containing product, Epidiolex, into Schedule V (classified as having low potential for abuse) so that it could be manufactured in the U.S. following a recent Food and Drug Administration (FDA) approval. Epidiolex is a pure, standardized form of CBD indicated for the treatment of two severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. Approval for Epidiolex by the FDA came in June of this year.

CBD is one of two natural compounds found in the marijuana plant, with the other being tetrahydrocannabinol (THC). THC is the psychoactive component of the plant, which causes the “high.” CBD is considered the less-addictive component that only stimulates the cannabinoid receptors 1 and 2 in the brain, but does not bind to them like THC. Currently, THC and all cannabis-derived CBD remains as a Schedule I substance. Due to potential benefits of CBD, it is often self-prescribed to treat conditions such as pain, depression, anxiety, Alzheimer’s and many others, although more clinical evidence is needed.

Epidiolex will be available in the market later this year as 100mg/ml drops in a 105ml bottle at a cost of $32,500 per year.  GW Research Ltd, manufacturer of Epidiolex, received FDA approval for the research and manufacturing of the drug, but was not able to release the product in the market until the DEA made its scheduling determination.

FDA Commissioner Dr. Scott Gottlieb emphasized that this is the only regulated and tested form of CBD that will be available in the market and that its efficacy and safety has been thoroughly investigated. In addition to four epilepsy trials to study the efficacy and safety of Epidiolex, the manufacturer also evaluated its potential for abuse and dependence. It had some abuse potential when tested at high doses, but less “liking” effect when compared to dronabinol (synthetic THC, Schedule III) and alprazolam (Schedule IV). Subjects did not show any signs of dependence over a six-week period following discontinuation of the drug.

While it might be considered a relatively safer alternative to other forms of marijuana, Epidiolex still has the potential for severe side effects, especially when taken at the maximum recommended dose of 20mg/kg/day compared to 10mg/kg/day. It is not recommended for people with hepatic disease, and caution is advised when combined with alcohol or other central nervous system (CNS) drugs such as opioids and benzodiazepines. It has a very high incident of drug-drug interaction with medications such as morphine, lorazepam, nicotine, anticonvulsants and certain antidepressants. Dose adjustment is recommended for other medications that interact with Epidiolex.

While the use of marijuana and its components is still controversial, clinical evidence does demonstrate Epidiolex’s effectiveness to treat certain types of seizures. Despite being a Schedule V drug, which indicates a lesser potential for abuse, it still carries a lot of warnings and concerns that we must consider before using it for our patient population. It is currently only studied and approved for these specific, rare epilepsy disorders.

With the scheduling determination of CBD with <0.1% THC as Schedule V, it will not be surprising to see more drugs in the pipeline in near future. GW Pharmaceuticals has looked at cannabis-based medicine (Sativex) for the treatment of chronic rheumatoid arthritis pain, but the results were inconclusive and warranted further research. Until we have some concrete evidence, the use of marijuana or any of its components is not recommended to treat chronic pain, and there is no standardized CBD product in the market that is FDA indicated for such use.


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