For patients with cancer, marijuana may be valuable in controlling pain and chemotherapy-induced nausea and vomiting. Furthermore, it may have efficacy as an appetite stimulant. No randomized clinical trial has investigated the utility of whole-plant medical marijuana to alleviate these symptoms in patients with cancer, however. Research by clinical and basic scientists in the United States is needed to identify the appropriate dose of the drug and its appropriate use in symptom and disease management. First, however, the federal government needs to remove marijuana from a schedule I category in the Federal Controlled Substances Act so that such research can be performed.
Marijuana may be helpful in controlling pain and chemotherapy-induced nausea and vomiting.— Richard J. Boxer, MD
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Marijuana has been used by man for thousands of years. It has been smoked, eaten, vaped, and rubbed, but never thoroughly studied in clinical or basic science research. Medical marijuana is available to millions of Americans who live in states where adult use is legal. This is despite the fact that the drug has not received U.S. government approval. In 1973, when President Richard Nixon declared a war on drugs and expanded the U.S. Food and Drug Administration (FDA), the marijuana plant was classified as a schedule I drug among far more dangerous drugs (ie, heroin and LSD). Schedule I drugs are those having no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.
Reputation as ‘Gateway Drug’ Lingers
The declaration of marijuana as a “gateway drug” has further vilified it. Even though the Institute of Medicine has refuted the myth of marijuana being a gateway drug, its reputation as such lingers. In 1999, the Institute of Medicine stated: “There is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.1” But research from Israel has started not only to dispute many of the unproven (yet promoted by many), unfounded pronouncements about marijuana, and it has begun to define advantages of the chemicals within the marijuana plant.2
FDA Controlled Substance Schedules
Schedule I Controlled Substances
The National Institute on Drug Abuse has promoted some sobering data about marijuana, purporting that 30% of those who use marijuana may have some degree of marijuana use disorder. People who begin using marijuana before the age of 18 are four to seven times more likely to develop a marijuana use disorder than adults. Estimates of the number of people addicted to marijuana are controversial, in part because epidemiologic studies of substance use often consider dependence as a proxy for addiction, even though it is possible to be dependent without being addicted.3 Furthermore, the National Institute on Drug Abuse quoted studies suggesting 9% of people who use marijuana will become dependent on it, rising to about 17% in those who start using marijuana in their teens.4
In 2015, about 4 million people in the United States met the diagnostic criteria for a marijuana use disorder, but just 138,000 of these individuals voluntarily sought treatment for their marijuana use.4,5
Closer Look at the Science
Humans have an endocannabinoid system that affects nearly all parts of the body. This system is a network of receptors spread throughout the entire body that control some of the most vital functions, including the immune system, memory, appetite, sleep, mood, and pain sensation. Receptors have also been found to impact metabolism, movement, temperature, learning, inflammation, neural development, neuroprotection, cardiovascular function, digestion, and reproduction. Thus, it is understandable why many research and clinical scientists are eager to have the federal classification of marijuana as a schedule I drug be removed so a thorough understanding of the substance could be achieved through research.
Within the marijuana plant, there are approximately 400 different chemicals. The chemicals familiar to most are tetrahydrocannabinol (THC), the cannabinol (CBN), and the mixed chemical, cannabidiol (CBD). There are many other chemicals within this family and subgroups as well, but I will focus on the common drug effects of these familiar chemicals.
Common effects of tetrahydrocannabinol are euphoria and relaxation, sleep and drowsiness, appetite stimulant, pain relief, antiemetic, and muscle relaxant. Some effects of cannabidiol may include antianxiety, neuroprotective, anticonvulsant, antipsychotic, pain relief, and anti-inflammatory. Thus, different concentrations of tetrahydrocannabinol or cannabidiol in the product to be consumed will cause a different effect on a patient’s diseases or symptoms.
For patients with cancer, marijuana may be helpful in controlling pain and chemotherapy-induced nausea and vomiting. Furthermore, it may have efficacy as an appetite stimulant.
Furthermore, the National Academies of Science, Engineering, and Medicine studied available data and stated there is conclusive evidence that cannabis has a therapeutic effect on chronic pain, multiple sclerosis muscle spasms, as well as chemotherapy-induced nausea and vomiting, and it does not cause cancer.6 The National Academies of Science, Engineering, and Medicine also noted that there is no conclusive evidence that marijuana reduces, causes, improves, or worsens heart attacks, strokes, diabetes, respiratory diseases, immune competence, and testicular cancer.7 Marijuana is, however, potentially detrimental to mental health (schizophrenia, social anxiety disorders, depression) as well as prenatal, perinatal, and neonatal care. It is also detrimental to driving.
Marijuana and the Opioid Crisis
Cannabis may be helpful in the socially devasting opioid crisis. The statistics are frightening: In 2017, more than 64,000 Americans died of a drug overdose. More than 650,000 total prescriptions for opioids are written every day. The epidemic will continue in the months and years ahead without appropriate interventions to halt the widespread growth.
In the four articles addressing cannabinoids in cancer care in this issue of The ASCO Post conclusions may differ on the efficacy of cannabinoids in controlling chemotherapy-related nausea and vomiting and other effects of cancer and its treatment. This may be due in part to differences in the evidence reviewed, differences in individual perspectives, differences in the characteristics of cannabis or cannabinoid exposure (ie, oral cannabinoids, marijuana plant, other formulations), among other differences.
These articles are not intended to accept or reject the associated risks and benefits of cannabinoids in cancer care. Rather, these articles are intended to call attention to the need for more research on the use of medical marijuana in oncology. Marijuana is legal in many states, and patients may ask their clinicians about the drug’s role in their care. Oncologists need to be able to provide informed guidance and evidence-based care for their patients with cancer.
According to an article in JAMA Internal Medicine several years ago, “States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate compared with states without medical cannabis laws.”8 In addition, researchers from the University of California San Diego found that hospitalization rates of people suffering from opioid painkiller dependence and abuse dropped 23%, and opioid overdoses requiring hospitalization fell 13%, in states after marijuana was permitted for medicinal purposes.9 A more recent study in Colorado, which legalized marijuana in 2014, demonstrated a 6.5% reduction in opioid-related deaths after recreational marijuana was legalized in the state.10 Nationwide, more than 4,000 lives might be saved if marijuana were available and used as a substitute for opioids.
Medical marijuana is currently available to Americans who live in states where adult-use marijuana is legal—approximately 20% of Americans.11 The plea from many patients, providers, and governmental officials is fundamentally the same: Remove marijuana from a schedule 1 category in the Federal Controlled Substances Act so research can be performed by clinical and basic scientists in the United States. Only then will clinicians be able to prescribe a drug that is already available to millions of Americans in an evidence-based manner, in the right dose, and for the right symptoms and diseases. ■
Dr. Boxer, a urologist practicing in Los Angeles, is affiliated with VA Greater Los Angeles Healthcare System. He also is Medical Director of iAnthus Capital.
This article was revised postpublication on 9/12/2018.
DISCLOSURE: Dr. Boxer is Medical Director of iAnthus Capital, a company that raises capital and invests in marijuana-licensed companies.
DISCLAIMER: The views expressed herein are those of the author and not necessarily the views of ASCO or The ASCO Post.
2. Abuhasira R, Schleider LB, Mechoulam R, et al: Epidemological characteristics, safety and efficacy of medical cannabis in the elderly. Eur J Intern Med 49:44-50, 2018.
3. National Institute on Drug Abuse: The neurobiology of drug addiction. Available at www.drugabuse.gov/publications/teaching-packets/neurobiology-drug-addiction/section-iii-action-heroin-morphine/10-addiction-vs-dependence. Accessed August 6, 2018.
4. National Institute on Drug Abuse: Is marijuana addictive? Available at www.drugabuse.gov/publications/research-reports-mariuana/marijuana-addictive. Accessed August 6, 2018.
5. National Institutes of Health: Marijuana use disorder is common and often untreated. Available at www.nih.gov/news-events/news-releases/marijuana-use-disorder-common-often-untreated. Accessed August 6, 2018.
6. National Academics of Sciences, Engineering, and Medicine: The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research (2017). Available at www.ncbi.nlm.nih.gov/books/NBK425767//. Accessed August 6, 2018.
7. National Academics of Sciences, Engineering, and Medicine: Nearly 100 conclusions on the health effects of marijuana and cannabis-derived products presented in New Report: One of the most comprehensive studies of recent research on health effects of recreational and therapeutic use of cannabis and cannabis-derived products. Available at www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=24625. Accessed August 6, 2018.
8. Bachhuber MA, Saloner B, Cunningham CO, et al: Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med 174:1668-1673, 2014.
9. Cohen R: Would legalizing medical marijuana help curb the opioid epidemic? Reuters Health News, March 27, 2017. Available at https://www.reuters.com/article/us-health-addiction-medical-marijuana/would-legalizing-medical-marijuana-help-curb-the-opioid-epidemic-idUSKBN16Y2HV. Accessed August 6, 2018.
10. Livingston MD, Barnett TE, Delcher C, et al: Recreational cannabis legalization and opioid-related deaths in Colorado, 2000-2015. Am J Public Health 107:1827-1829, 2017.
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