The current regulatory and legal landscape for cannabis and cannabis-derived products is extremely difficult and fraught with numerous challenges. For example, in the US, cannabis and products derived from it (including hemp) are federally classified as Schedule I drugs according to the US Controlled Substances Act (1). This means that cannabis and its products have been deemed to have “no currently accepted medical use in treatment in the US” (heroin and LSD are also schedule I drugs), are harmful and consequently, are illegal (2).
Not surprisingly, its Schedule 1 classification has seriously hindered cannabis research in the US and made it extremely challenging for drug companies developing cannabis-derived pharmaceutical products (3). However, over the past decade or so, 29 states including the District of Columbia have enacted legislation that permits some form of cannabis consumption for medical purposes (4). Yet, despite this, cannabis and products derived from it remain illegal at the federal level and during interstate transport (even between states where medical marijuana has been legalized) is illegal and criminally punishable (2).
The confusion regarding cannabis use at the state and federal levels has given rise to two distinct types of companies that are attempting to commercialize cannabis (and products derived from it) for medicinal purposes. The first of these are commonly referred to as medical marijuana or medical cannabis companies. Typically, products from these companies are botanical extracts or actual plant materials derived from specific cannabis strains with anecdotally-reported medicinal properties that can be topically applied, ingested, smoked or vaporized. Patients require a “prescription” (card) from a state-licensed physician to obtain medical marijuana and it can only be used in states that permit consumption of cannabis for medical purposes. It is important to note, that while a prescription is required for medical cannabis use, these products do not require human clinical testing for safety, tolerability and efficacy (like other prescription drugs) prior to their sale in states where medical marijuana is legal.
In contrast with medical marijuana companies, biopharmaceutical companies including GW Pharma, Zynerba, Insys, Kannalife, Aphios and others (Table 1) are committed to developing cannabis-derived pharmaceuticals using conventional US Food and Drug Administration regulatory approval pathways. UK-based GW Pharma is the clear leader in cannabis-derived pharmaceutical space—its flagship product Sativex®, a plant extract, has been approved as a treatment for cancer-related pain and MS spasticity in 27 countries outside the US (5).
While the business case for developing pharmaceutical cannabis-derived pharmaceuticals is a sound one, the time and cost necessary for regulatory approval will be much greater than that for commercializing medical marijuana. At present, the United State Food and Drug Administration (FDA) has signaled a willingness to review new drug applications for cannabis-based pharmaceuticals (6). However, the agency has yet to issue definitive guidance for regulatory approval of these products and to date has not approved any application for cannabis-based products (6). Nevertheless, garnering FDA regulatory approval for cannabis–derived pharmaceuticals may offer several competitive advantages over numerous medical marijuana products that currently dominate the US market.
First, the average cost per patient of Sativex® to treat MS spasticity in countries where it has been approved has been estimated to be roughly $16,000 (6). Several studies indicate (7, 8) that the high price of Sativex® will make it unlikely to be considered cost effective by regulators in countries with government-mandated national formularies like the UK, Ireland and Australia. However, this should not be an impediment in the US market because the federal government does not set drug prices and third-party payers dictate formulary placement and set drug reimbursement rates.
Second, unlike medical marijuana (which as previously state is a Schedule 1 drug), FDA approved cannabis-based pharmaceuticals like dronabinol and nabilone have been classified or reclassified as Schedule 2 (opioids) or Schedule 3 (codeine) drugs (5, 9). Federal regulators are likely to apply the same scheduling criteria to the next generation of FDA-approved cannabis-derived pharmaceuticals like Sativex® and others. Rescheduling will effectively allow these products to compete with medical marijuana because unlike medical marijuana—which is legal in only 29 states and cannot be transported across state borders—approved cannabis-derived pharmaceuticals can be legally prescribed, sold and used in all 50 states and US territories.
Finally, and perhaps most importantly, physicians may be inclined to prescribe FDA-approved cannabis drugs as compared with medical marijuana because they have been evaluated in human clinical trials and officially deemed to be safe and effective treatments for specific therapeutic indications.. In marked contrast, medical marijuana can be prescribed and sold in states where it is legal without going through any formal drug review process. While this is unlikely to interfere with possible therapeutic benefits offered by medical cannabis questions concerning product safety, effectiveness and reproducibility about these products are likely to continue to arise until industry best practices are implemented and standardized.
- https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm Accessed July 17, 2017
- https://www.dea.gov/druginfo/ds.shtml Accessed July 17, 2017
- https://www.brookings.edu/wp-content/uploads/2016/06/Ending-the-US-governments-war-on-medical-marijuana-research.pdf Accessed July 17, 2017
- http://medicalmarijuana.procon.org/view.resource.php?resourceID=000881 Accessed July 17, 2017
- https://www.gwpharm.com/products-pipeline/sativex Accessed July 17, 2017
- https://www.fda.gov/newsevents/publichealthfocus/ucm421163.htm Accessed July 17, 2017
- Pharmacoeconomic NCF. Cost-effectiveness of Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®) as add-on treatment, for symptom improvement in patients with moderate to severe spasticity due to MS who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy. 2014. http://www.ncpe.ie/wp-content/uploads/2013/01/Summary-v1.pdf.
- Lu L, Pearce H, Roome C, Shearer J, Lang IA, Stein K. Cost effectiveness of oromucosal cannabis-based medicine (Sativex(R)) for spasticity in multiple sclerosis. PharmacoEconomics. Dec 1 2012;30(12):1157-1171.
- https://www.deadiversion.usdoj.gov/fed_regs/rules/1998/fr1105.htm Accessed July 17, 2017