Because of historical negative perceptions and ongoing legal concerns, only a few cannabis-based pharmaceuticals are currently licensed for clinical use. In the United States and Europe the synthetic Δ-9-THC drugs nabilone (Cesmet®) and dronabinol (Marinol®) and dronabinol (Marinol®) are approved for treatment and prevention of chemotherapy-induced nausea and vomiting (CINV; 1). Another synthetic Δ-9-THC product, Syndros (dronabinol oral solution) received approval in 2016 for the treatment of anorexia associated with weight loss in patients with AIDS and for cancer patients with CINV who failed to adequately respond to conventional antiemetic treatments.
GW Pharmaceuticals’ Sativex®, an extract containing THC and CBD, is approved in 27 countries Europe and elsewhere for the treatment of spasticity associated with multiple sclerosis and, in Canada, is also approved as an adjunctive treatment for cancer pain (1) The CB1 cannabis receptor agonist rimonabant (Acomplia®) was approved for use in Europe to treat obesity but was discontinued because of serious adverse effects (2)
While the approved cannabis-based pharmaceutical list is quite short, there are several compounds and extracts that are currently being evaluated in human clinical trials for regulatory approval. Sativex®, which received FDA fast track designation, has completed Phase 3 clinical testing and an application for approval has been filed at FDA. Another GW Pharmaceuticals product called Epidiolex® received FDA orphan drug status and is currently in mid to late stage clinical testing as a treatment for orphan pediatric epilepsy including Dravet Syndrome and Lennox Gastaut syndrome
Other companies, including Arena Pharmaceuticals, are attempting to develop cannabis-based drugs and mimetics that treat pain by binding to certain types of cannabis receptors found throughout the body (3). Removing cannabis’ psychotropic effects and preserving its pain-relieving benefits is the major objective for this new class of pharmaceuticals. Although these drugs are still in early stages of development, using them rather than addictive opioids to manage chronic pain would be an important step in combating the US opioid epidemic.
Although the future of cannabis-based pharmaceuticals in the US is brighter than it has been over the past 50 years, there are still some major hurdles and obstacles that must be overcome. To gain some insight into some of these, please read 2015 testimony to Congress given by Douglas C. Throckmorton, M.D. Deputy Director for Regulatory Programs Center for Drug Evaluation and Research Food and Drug Administration.
Moreover, the approval process for cannabis-based pharmaceuticals has an additional layer of complexity as compared with conventional pharmaceuticals. Because cannabis and its products are classified as Schedule 1 drugs according to the US Drug Enforcement Agency (DEA), a product that garners FDA approval must also be reviewed by DEA for scheduling recommendations. To that end, FDA usually provides DEA with a scientific and medical evaluation to help with scheduling. Scheduling classification is important because it affects the controls necessary for prescribing, supplying, or storing the product. At present cannabis’ Schedule 1 status means that it and any products derived from it have no medicinal value or benefit and consequently are illegal in the US. Nevertheless, it is extremely likely that any newly approved cannabis-based pharmaceuticals will be rescheduled as Schedule II or Schedule III drugs as was FDA’s previous experience with nabilone, dronabinol and Syndros. That said, permanently removing cannabis and its products form the Schedule 1 list would undoubtedly help to speed development and subsequent regulatory approval of potentially life-altering cannabis-based pharmaceuticals.
- Ladin, DA, Soliman E, Griffin L and Van Dross, R. Preclinical and clinical assessment of cannabinoids as anti-cancer agents. Front Pharmacol. Oct. 2016; 7: 361 DOI: 10.3389/fphar.2016.00361
- Fijal, K, Filip M. Clinical/therapeutic approaches for cannabinoid ligands in central and peripheral nervous system diseases: mini review. Clin Neuropharmacol 2016; 39:94-101.
- Mintz CS, Fabrizio AJ, Nison E. Cannabis-Derived Pharmaceuticals. J. Comm. Biotechnol. 2015; 21:16-30.