Medical Marijuana: Where Do We Stand Today?By Eellan Sivanesan, MD, Andrea L. Nicol, MD, MSc Jun 22, 2016
Medical marijuana is no longer a taboo topic or exclusive to a minority of states. As of 2015, more than 30 states and the District of Columbia have legalized the use of marijuana for medicinal purposes with varying restrictions (Table 1). This number is forecast only to grow as other states continue to vote on this issue. The question of legalization may soon be replaced by the question of how we will implement safe use criteria. If marijuana will be treated as a prescription medication, it makes sense that it will also have to conform to the same safety standards set for other medications.
A clinical conundrum surrounds this issue as the United States Food and Drug Administration (FDA) has not officially approved the use of marijuana as a safe and effective drug for any indication. Although some synthetic derivatives have been approved, mainly for cancer-related indications, this statement applies to the most frequently used form: botanical marijuana. Thus, it appears that a number of states are allowing the use of medical marijuana, including botanical marijuana, without official FDA approval. The FDA does, however, have a clause that allows patients the ability to access drugs currently under investigation. While a patient is certainly able to use an investigational substance if enrolled in a clinical trial, the Expanded Access or “Compassionate Use” policy bases the use of an investigational substance outside of a clinical trial if the following criteria are met:
- “The person’s physician determines that there is no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat the person’s disease or condition, and that the probable risk to the person from the investigational product is not greater than the probable risk from the disease or condition;
- FDA determines that there is sufficient evidence of the safety and effectiveness of the investigational product to support its use in the particular circumstance;
- FDA determines that providing the investigational product will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval; and
- The sponsor (generally the company developing the investigational product for commercial use) or the clinical investigator submits a clinical protocol (a document that describes the treatment plan for the patient) that is consistent with FDA’s statute and applicable regulations for investigational new drugs (INDs) or investigational device exemption applications (IDEs), describing the use of the investigational product.”
After receiving much scrutiny in the lengthy process for obtaining approval, the FDA has attempted to create a more streamlined process to reduce paperwork fatigue with the creation of FDA Form 3926.
The numerous other agencies involved with regulation add even further complexity and include the National Institute on Drug Abuse, the National Cancer Institute, the Drug Enforcement Agency, and several other federal agencies. Since the regulations are actively changing, it is of utmost importance for prescribers to keep up to date. The Compassionate Access, Research Expansion, and Respect States Act is a bill currently under consideration in Congress that would render the Controlled Substances Act, which provides the current federal ban on marijuana, inapplicable if in disagreement with state law. In addition, this bill would reclassify marijuana from a schedule I to a schedule II substance, expand veteran access, and alter banking regulations hindering marijuana businesses.4 Marijuana has been illustrated in several studies to have a synergistic effect with opioids related both to its analgesic properties and adverse reactions.[5,6] Controversy exists as to hether this relates to an increased potential for abuse; however, a recent study noted that opioid overdose mortality rates were lower in states where medical marijuana is legal. Although no current evidence-based guidelines exist in legalized states when applying this dual therapy, it appears that concurrent therapy may allow decreased opioid dosing. Synthetic derivatives of marijuana, particularly the cannabinoid derivatives, hold promise as more selective agents that potentiate analgesia while avoiding many of the symptomatic adverse effects associated with other forms such as botanical marijuana and derivatives containing delta-9-tetrahydrocannabinol.
Once the regulatory maze has been negotiated and patients are prescribed marijuana, how do we monitor its safety profile? Can it be safely prescribed with other medications, particularly opioids? How do we assess that the prescription is not being diverted? Is there a suggested dose range for these agents? If so, how are estimates made when using botanical marijuana? Is this a “gateway” substance that necessitates routine screening for illicit substances? Which activities should we caution against while medicating with marijuana? These are just a few of the dilemmas
associated with marijuana prescription. Unfortunately, these questions are not easily answered and will most likely be resolved on a case-by-case basis. The continued growth of the marijuana industry is a signal that this topic can no longer be avoided. Just as we would for any other medication, particular those with abuse potential, we must devise appropriate monitoring and dosing standards to keep patient safety a priority.
- National Organization for the Reform of Marijuana Laws. State laws. 2016. Available at: http://norml.org/laws. Accessed March 10, 2016.
- U.S. Food and Drug Administration. Expanded access (compassionate use). Updated February 19, 2016. Available at: http://www.fda.gov/NewsEvents/ PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm. Accessed March 10, 2016.
- U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Individual Patient Expanded Access Applications: Form
3926. February 2015. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM432717.pdf.
- Compassionate Access, Research Expansion, and Respect States Act of 2015,
S.683, 114th Congress (2015–2016).
- Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90(6):844–851.
- Tham SM, Angus JA, Tudor EM, Wright CE. Synergistic and additive interactions of the cannabinoid agonist CP55, 940 with μ opioid receptor and α2-adrenoceptor agonists in acute pain models in mice. Br J Pharmacol.
- Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668–1673.
- Hosking RD, Zajicek JP. Therapeutic potential of cannabis in pain medicine. Br J Anaesth. 2008;101(1):59–68.
Eellan Sivanesan, MD, PGY4, is the ASRA Resident/Fellow Section Committee Chair 2016-2017 and works in the department of Anesthesiology, Perioperative Medicine, and Pain Management at the University of Miami/Jackson Memorial Hospital, Miami, FL.
Andrea L. Nicol, MD, MSc, is an assistant professor in the Department of Anesthesiology at the University of Kansas School of Medicine in Kansas City, KS.
Note: This article originally appeared in the ASRA News, Volume 16, Issue 2, pp. 15-16 (May 2016).