On June 25, 2018, the U.S. Food and Drug Administration (FDA) approved Epidiolex (cannabidiol, or CBD) oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. In addition to ushering in the first-ever approved drug for Dravet syndrome, the greenlighting of Epidiolex marks the first time the FDA has approved a drug comprised of an active ingredient derived from marijuana.
The drug is made from purified CBD, which does not cause the mind-altering high that comes from tetrahydrocannabinol (THC), the main psychoactive component of marijuana. According to FDA Commissioner Scott Gottlieb, M.D., “This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies.”[1]
The medical possibilities of cannabis, cannabinoids, and the body’s natural endocannabinoid system inside the brain and nervous system are currently being explored in nearly 700 studies, according to the clinical trial registry of the National Institutes of Health (NIH). According to the U.S. Drug Enforcement Agency (DEA), more than 590 researchers as of December 2017 were registered to conduct scientific research with Schedule I controlled substances, including cannabis/marijuana, cannabis/marijuana extracts and derivatives, and THC.
This represents an increase of more than 60 percent from the 350 researchers who were registered in August 2016.[2] To date, at least 113 different cannabinoids have been isolated from the cannabis/marijuana plant. The best-studied cannabinoids include CBD, THC, and cannabinol (CBN). There is also significant research into the human endocannabinoid system and its involvement in a variety of physiological processes including appetite, pain-sensation, mood, and memory, as well as its role in mediating the psychoactive effects of cannabis/marijuana.
Broadly, the FDA, DEA, and other federal agencies have publicly signaled support for clinical research into cannabis/marijuana and its components. In 2016, the DEA changed the federal government’s long-standing policy to allow for a larger number of DEA-registered marijuana manufacturers to supply registered scientific researchers in the United States. In January 2018, the DEA also rolled out a dedicated web portal and online application process for researchers wishing to register with the agency to study Schedule I substances.[3]
With regard to the FDA, the approval of Epidiolex demonstrates the FDA’s commitment to supporting rigorous scientific research on the potential medical applications of marijuana-derived products and working with sponsors to bring safe, effective, high-quality products to market. As of June 30, 2018, 30 U.S. states and the District of Columbia have legalized the use of medical marijuana. Nine states and D.C. have gone one step further and legalized recreational marijuana use as well.
However, marijuana/cannabis-related medical research remains federally regulated. Currently, conducting clinical research using marijuana, cannabis, or its cannabinoid components is challenging, involving coordinated interactions with no less than three U.S. federal agencies. This involves:
- Obtaining the marijuana for research from the National Institute on Drug Abuse (NIDA) within the National Institutes of Health
- Undergoing review of an investigational new drug (IND) application and research protocol by the FDA
- Obtaining clinical investigator registration and clinical research site licensure from the DEA
The DEA has publicly stated its support of legitimate medical and scientific research on marijuana and its constituent parts along with its commitment to finding ways to make the research process more efficient and effective. Thus far, however, the agency has refused to remove marijuana/cannabis from its list of highly restricted and regulated Schedule I drugs under the 1970 U.S. Controlled Substances Act (CSA) as some scientific, medical, and political communities most recently requested, but failed to push through, in 2016.
Given that the approval of Epidiolex has assigned an accepted medical use to marijuana/cannabis, the DEA will likely need to make a different scheduling decision for CBD. For now, the FDA is encouraging clinical researchers seeking to use cannabis/marijuana to develop a potential new therapy to follow its August 2015 guidance on the use of botanicals [PDF].
While Epidiolex is the first plant-derived CBD medicine for prescription use in the U.S., the FDA previously approved two man-made marijuana-based drugs for medical use: Marinol (dronabinol) for nausea from cancer chemotherapy and Cesamet (nabilone) for nausea and neuropathic pain. The approval of Epidiolex will pave the way for more research into cannabis-derived or cannabis-based therapies, potentially opening the door for further treatments.
[1] U.S. Food and Drug Administration. FDA approved first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611046.htm. Accessed July 13, 2018.
[2] U.S. Drug Enforcement Administration. DEA Announces Actions Related to Marijuana and Industrial Hemp. Available at https://www.dea.gov/divisions/hq/2016/hq081116.shtml. Accessed July 13, 2018.
[3] U.S. Drug Enforcement Administration. DEA speeds up application process for research on Schedule I drugs. Available at https://www.dea.gov/divisions/hq/2018/hq011818.shtml. Accessed July 13, 2018.