Medical Marijuana Use in Oncology : A Review
Gianna Wilkie, Bachir Sakr, Tina Rizack
JAMA Oncology, 2016, 2, (5), 670-675.
IMPORTANCE : Medicinal marijuana use is currently legal in 23 states and the District of Columbia. As more states approve marijuana use for medical indications, physicians will be asked by their patients for more information regarding the risks and benefits of use. This article reviews the history, adverse effects, and proposed mechanisms of action of marijuana and summarizes the available literature regarding symptom relief and therapeutic value in patients with cancer.
OBSERVATIONS : Marijuana in oncologymay have potential for use as an antiemetic, for refractory cancer pain, and as an antitumor agent. However, much of the data are based on animal data, small trials, or are outdated.
CONCLUSIONS AND RELEVANCE : More research is needed in all areas related to the therapeutic
use of marijuana in oncology.
Medical marijuana use is controversial in American society. While states move to legalize marijuana for medical and/or recreational use, research is needed to elucidate the adverse effects and potential therapeutic benefits of cannabis therapy. This literature review focuses on the history of marijuana use, potential mechanisms of action, the therapeutic use of marijuana in oncology, and its adverse effects.
History and Legal Status
Cannabis has a history of both medicinal and recreational use dating back centuries.Tradition holds that Chinese Emperor ShenNung touted the benefits of cannabis in the 28th century BC.1 Cannabis was believed to have healing powers for ailments including rheumatism, gout, malaria,and“absent mindedness.”2 In 1611, the Jamestown settlers brought marijuana (commonly known as hemp) to North America, and throughout the colonial period hemp fiber was an important export.2 Cannabis was first introduced to Western medicine by surgeon W.B.O’Shaughnessy in the 1840s. While working for the British East India company, he reportedly found it to have good analgesic, anti-inflammatory, antispasmodic, and anticonvulsant properties. During this same time, a French psychiatrist, Jacques-
Joseph Moreau, conducted studies that found that marijuana use suppressed headaches, increased appetite, and aided sleep. Marijuana was introduced into the US Pharmacopeia in 1850 and was prescribed for conditions such as labor pain, nausea, and rheumatism.2
The passage of the Harrison Act of 1914 defined the use of marijuana as a crime, which led individual states such as California and Texas to pass laws prohibiting marijuana use for nonmedical purposes.3 TheUS Congress then passed the Marijuana Tax Act, criminalizing the drug in 1937.3 (pp971-1203) It was removed from the US Pharmacopeia in 1941 because it was no longer recognized to have medicinal use.2 The Boggs Act and Narcotics Control Act of 1951 increased marijuana possession and distribution penalties and led to the enforcement of mandatory prison sentences.3 (pp971-1203) In 1970, marijuana became a Schedule I drug,4 a classification given by theUS Drug Enforcement Administration to drugs with no currently accepted medical use with a high potential for abuse.5 In1986, the Anti–Drug Abuse Act was passed, reinstating mandatory minimum penalties and increasing federal penalties for both possession and distribution of marijuana.6(pp189-190) It was not until 1996 that California became the first state to relegalize marijuana for use by people with AIDS, cancer, and other serious illnesses.6(p321) In 2010, California rejected proposition 19, which would have legalized marijuana use for recreational purposes.7 (pp159-215) In November of 2012, the passage of Colorado’s Amendment 64 and Washington’s Initiative 502 made them the first US states to pass recreational use laws.8 Currently, 23 states and the District of Columbia have laws legalizing marijuana use in some form, with 4 states and the District of Columbia legalizing marijuana for recreational use (Table).8
The current state of cannabis use for both medical and recreational purposes in the United States is highly debated. While it is still classified as an illegal substance federally, many states have moved to decriminalize and/or legalize marijuana for medical and/or recreational use.9 Despite limited research on the effects of smoked cannabis, states appear to be motivated to legalize marijuana use for financial gain. In 2010, it was predicted that legalizing marijuana use would generate $8.7 billion in annual federal and state tax revenues while saving billions of dollars that were previously spent for regulating marijuana use.10(pp1-62) The state ofWashington generated $70 million in tax revenue from marijuana sales in the first year of marijuana legalization.11 In addition, many states’ residents support marijuana legalization.11
With access to medical marijuana increasing, physicians maybe asked for prescriptions and information about this substance. Physicians have mixed attitudes about the legalization of medical marijuana use. In 2005, Charuvastra et al 12 sampled 960 physicians for their opinions about the legal prescription of marijuana as medical therapy. Their results showed that 36%of physicians believe marijuana use should be legal, while 26% were neutral to the proposition. In 2013, Adler and Colber13 completed a poll of 1446 physicians and found that 76%approved of using marijuana for a medical purpose. Most physicians in this study cited their “responsibility as caregivers to alleviate suffering” as their reason for support. The American Medical Association has stated that itwould support marijuana rescheduling if it facilitated research and the development of cannabinoid-based medicine.14
Mechanism of Action
The exact mechanism of action of cannabis remains unclear. Cannabis is composed of 3 different bioactive molecules called flavonoids, terpenoids, and cannabinoids. The most well-studied cannabinoid is Δ9-tetrahydrocannabinol (THC), the most active constituent of the plant. Small alterations in the structure of cannabinoids, such as THC, can dramatically change their potency.15 Cannabis exerts its actions by binding to specific receptors called cannabinoid receptors, making up the endogenous cannabinoid system. Devane et al16 characterized the cannabinoid receptor, whereas Compton et al17
showed a strong correlation between the binding affinity for the receptor site and the corresponding potency of a large number of cannabinoid analogs. These receptors, called cannabinoid receptors 1 and 2 (CB1 and CB2),work via their action as G-protein coupled receptors, wherethey inhibit both adenylate cyclase and calcium channels and activate in wardly rectifying potassium channels.18