As of February 2022, 37 states along with the District of Columbia have legalized medical cannabis, and 19 states plus the District of Columbia have legalized adult-use cannabis.
Unsurprisingly, the use of cannabis in patients with cancer appears to be increasing as more and more states are adopting cannabis legislation, both for medical and adult use.
Moreover, in addition to increased cannabis legalization, there has been an explosion of cannabidiol and other non-impairing cannabinoids that hit the market—thanks to the 2018 Farm Bill, which descheduled hemp.
With nearly two-thirds of the states allowing for medical cannabis use and the legalization of hemp, accessing cannabinoids has become much easier, especially for patients with cancer, which is a qualifying condition in almost every state. The increased access to cannabinoids has led to patients’ curiosity. Many of these patients are seeking symptom relief with cannabis and are turning to their oncology care team for further guidance.
Yet, many oncology professionals have had little to no education on cannabis.
In survey findings published in the Journal of Clinical Oncology in 2018, 70% of medical oncologists felt unequipped to make clinical cannabis recommendations, and 46% of oncologists are recommending cannabis for symptom relief even though they have had no formal training.2 Additionally, an estimated 20% to 40% of patients with cancer are consuming some form of cannabis either during or after treatment—and that number may be underreported in states where cannabis is not legal.3
Cannabis Research in Oncology
Uncertainty exists among the different types of cannabis and whether clinical evidence supports cannabis use in certain medical conditions. Research is limited due to the federal designation of cannabis as a Schedule I drug.
Despite this restriction, there is sufficient evidence in some areas to demonstrate that cannabinoids may have a therapeutic effect. In 2017, the National Academy of Sciences, Engineering, and Medicine released The Health Effects of Cannabis and Cannabinoids report, which followed a review of more than 10,000 peer-reviewed journals. The authors concluded the following4:
1. Conclusive evidence suggests that cannabis or cannabinoids are effective at treating chronic pain in adults with chemotherapy-induced nausea and vomiting.
2. Moderate evidence suggests that cannabis or cannabinoids are effective at improving short-term sleep disturbances, and limited evidence suggests effectiveness at improving appetite and decreasing weight loss.
3. There is insufficient evidence to demonstrate whether cannabis or cannabinoids are effective or ineffective in treating patients with gliomas or cancer-associated anorexia-cachexia.
Despite the comprehensive review of the literature, generalized anxiety disorder and chemotherapy-induced peripheral neuropathy were not addressed. However, the report highlighted the need for more clinical research to better understand the therapeutic effects of cannabinoids in certain diseases.
Even though limited data support the use of cannabis as a first-line treatment in cancer-related symptoms, many patients are using it to relieve anxiety, pain, nausea, vomiting, and insomnia. In a recent Cancer study, 42% of 612 patients with breast cancer reported using cannabis for symptom relief.5 Seventy-eight percent used it to help with pain, 70% for sleep, 57% for anxiety, and 46% for nausea and vomiting relief.
Data also found that 39% of participants discussed their cannabis use with their physicians and that when they did, it was initiated by the patient 76% of the time. Moreover, only 4% of respondents listed their physician as the most helpful source of information on cannabis, instead listing the internet (22%), family members (18%), and dispensary staff (12%) as a more helpful source of information. This trend is concerning, considering that the internet is not always an accurate or reliable source of information and that dispensary staff often have no medical background and little cannabis education.
Oncology professionals can start to address patient questions and concerns by educating themselves on the endocannabinoid system, cannabinoids, routes of administration, dosages, potential drug-drug interactions, adverse effects, and common cancer-related uses and considerations.
Unfortunately, this information is not widely taught in medical or nursing schools, and without standardized cannabis education, clinicians are self-selecting sources to decrease their knowledge gap. Foundational knowledge of key concepts can allow oncology professionals to better guide patients to safe and effective use.
The Endocannabinoid System
Discovery of the first cannabinoid receptor in 1988 led to detection of the endocannabinoid system (ECS). The ECS, of which the main function is to maintain homeostasis, is a molecular signaling system that consists of 2 cannabinoid receptors (most commonly CB1 and CB2), ligands, and enzymes that normalize sleep, pain perception, memory, mood, and appetite. These receptors can be stimulated by human endogenous cannabinoids as well as plant-derived cannabinoids (phytocannabinoids) and synthetic cannabinoids.6
CB1 and CB2 are known as G protein–coupled receptors, and CB1 receptors are found predominantly in the adrenal glands, heart, kidneys, prostate, pancreas, colon, liver, central and peripheral nervous systems, lungs, testes, and ovaries. Upon CB1 receptor activation, the CB1 receptors assist in relief from depression, anxiety and stress, pain and inflammation, neurodegenerative disorders, posttraumatic stress, and multiple sclerosis–related symptoms.6
CB2 receptors are also detected in the brain and peripheral nervous systems. However, these are mostly contained in the peripheral immune cells. These receptors are found in the brainstem neurons, lungs, microglia, and uterus. Upon activation, CB2 receptors are known to reduce inflammation and treat mental health disorders and neurologic diseases such as Alzheimer, Parkinson, Huntington, and multiple sclerosis.6
Cannabinoids are defined as chemical compounds, which can be plant-derived (phytocannabinoids), synthetic, or endogenous, with the ability to influence the cannabinoid receptors while promoting neurotransmitter release. D-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) are the 2 most commonly known cannabinoids, the first of which is primarily responsible for the euphoric effects of cannabis. Behavior, consciousness, mood, and perception are all altered by Δ-9 THC, which binds to CB1 receptors in the brain and causes a change to the function of the binding cell. Studies have suggested efficacy when using Δ-9 THC to treat the following conditions7-18:
› Appetite loss
› Sleep apnea
› Posttraumatic stress disorder
CBD is typically the second most abundant cannabinoid in cannabis. It is psychoactive but not in the same manner as THC. It can alter mood, perception, and decrease anxiety. Studies have suggested that CBD can also treat patients with the following conditions19-24:
› Nausea and vomiting
› Seizure disorders
› Psychosis disorders
› Inflammatory disorders
› Neurogenerative disorders
THC and CBD can be found in the cannabis plant along with more than 100 other cannabinoids and can often be purchased through licensed dispensaries in legal states or through hemp retailers (online and in store). Phytocannabinoids are not standardized, and states can set their own limits on potency and testing. FDA pharmaceutical-grade THC is available via dronabinol, which is synthetic and has been approved as an antiemetic and appetite stimulant. Cannabidiol (Epidiolex) is a medication that is derived from the cannabis plant and approved by the FDA as an anticonvulsant. In states where cannabis is legal for medical or adult use, patients can explore cannabinoids for a variety of health conditions without FDA approval.
Cannabis Routes of Administration
Cannabis products offer various routes of administration, including topical, transdermal, inhalation, sublingual, and ingestion. Understanding the onset and duration of action can be helpful in determining which route will effectively treat patient symptoms. Unfortunately, products’ availability to patients depends on an individual state’s cannabis laws, and many state cannabis programs severely limit the product and formulary options.
Topical administration can provide localized relief within 15 minutes and often has little to no adverse effects (AEs). Upon activation, CB1 receptors on the skin assist in redness and inflammation reduction linked with conditions such as atopic and contact dermatitis and psoriasis. Evidence also suggests that topical cannabis can reduce arthritis-related pain and inflammation. There is little risk involved with this administration method.
Transdermal cannabis products—which are most commonly patches—are intended to penetrate the skin and reach the bloodstream and can provide between 6 and 12 hours of relief while avoiding first-pass metabolism. Transdermal products may be the optimal administration choice in patients whom drug interactions or medication adherence is a concern.
Inhalation provides relief quickly by reaching the bloodstream within minutes; this method is also found to be the most predictable while having the most control. It also provides a benefit for those who are unable to ingest other forms of medications. Chronic use has been associated with bronchitis and airway inflammation, so the benefit must outweigh the risk. Additionally, most indications for inhalation are short term.
Ingesting cannabis is a go-to choice for patients who suffer from chronic pain, inflammation, nausea, and insomnia because it can provide more durable and dependable relief. However, it does have variability in onset of action and is dependent on a patient’s metabolism, genetics, gender, and food intake. Taking these factors into consideration, the onset of action can range from 30 minutes to 2 hours or more. That being said, the effects of ingesting cannabis can last for at least 5 hours. Because of this factor, patients can overconsume and experience AEs, such as tachycardia, paranoia, hypotension, vomiting, and hallucinations. AEs associated with cannabis use are often from ingestible products. The use of the “go low and slow” method can help avoid some unwanted AEs associated with cannabis overconsumption.
Although drug interactions with cannabis are rarely hazardous, there is still potential for interactions to occur, especially with ingested cannabinoids. When taken orally, cannabinoids are metabolized by the cytochrome P450 (CYP) family of enzymes. THC is often metabolized by the CYP2C9, CYP2C19, and CYP3A4 enzymes, which convert THC into 11-hydroxy-THC. CBD, however, is commonly metabolized by the CYP2C19 and CYP3A4 enzymes, which convert CBD into 7-hydroxy-cannabidiol.25,26 Because most medications are metabolized by CYP3A4, CBD and THC can inhibit or induce other medications metabolized through that same
enzyme. Warfarin, among other medications, can inhibit or induce THC and CBD, which increases or decreases cannabinoid plasma levels.27 Cannabis should be used with caution with other central nervous system depressants, including alcohol, since it can generate sedative effects.
Cannabis dosing remains one of the most challenging components of providing care. Very few clinical trials have established dosing protocols with cannabinoids for specific conditions. As it stands, most dosing protocols have been developed from realworld evidence rather than evidence-based trials. The go-low-and-slow method is most applicable with cannabis. Because cannabinoids can have biphasic effects, a low dose is often sufficient for symptom relief.
Considerations for Patients With Cancer
With cannabis accessibility on the rise, many patients with cancer will be seeking guidance on the safe and effective use for symptom management. As cannabis research evolves and the industry matures, oncology professionals can look to cannabinoids as a potential supportive medicine. With proper guidance, cannabis can have a high safety profile with adverse effects that are generally well tolerated when administered at low doses. Patients are using it. Therefore, oncology professionals must be ready to meet the needs of their patients.
- State Medical Marijuana Laws. National Conference of State Legislatures. Updated February 3, 2022. Accessed February 4, 2022. https://www.ncsl.org/research/health/ state-medical-marijuana-laws.aspx
- Braun IM, Wright A, Peteet J, et al. Medical oncologists’ beliefs, practices, and knowledge regarding marijuana used therapeutically: a nationally representative survey study. J Clin Oncol. 2018;36(19):1957-1962. doi:10.1200/JCO.2017.76.1221
- Worster B, Handley N, Ashare R, Meghani SH. What do oncology providers need to know about cannabis use in patients with cancer? ASCO Daily News. September 2, 2021. Accessed October 25, 2021. https://dailynews.ascopubs.org/do/10.1200/ ADN.21.200700/full
- The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies of Sciences, Engineering, and Medicine; 2017. doi:10.17226/24625
- Weiss MC, Hibbs JE, Buckley ME, et al. A Coala-T-Cannabis survey study of breast cancer patients’ use of cannabis before, during, and after treatment. Cancer. Published online October 12, 2021. doi:10.1002/cncr.33906
- Theisen E. Medical Cannabis: What Nurses Need to Know. American Nurse. November 4, 2019. Accessed October 25, 2021. https://bit.ly/2Zs8GrK
- Musty RE, Rossi R. Effects of smoked cannabis and oral δ9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy. J Cannabis Therap. 2001;1(1):29-56. doi:10.1300/J175v01n01_03
- Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68(7):515-521. doi:10.1212/01.wnl.0000253187.66183.9c
- Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34(3):672-680. doi:10.1038/npp.2008.120
- Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182(14):E694-E701. doi:10.1503/cmaj.091414
- Abrams DI, Hilton JF, Leiser RJ, et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med. 2003;139(4):258-266. doi:10.7326/0003-4819-139-4-200308190-00008
- Fogarty A, Rawstorne P, Prestage G, Crawford J, Grierson J, Kippax S. Marijuana as therapy for people living with HIV/AIDS: social and health aspects. AIDS Care. 2007;19(2):295-301. doi:10.1080/09540120600841930
- Cousens K, DiMascio A. Delta 9 THC as an hypnotic. an experimental study of three dose levels. Psychopharmacologia. 1973;33(4):355-364. doi:10.1007/BF00437513
- Prasad B, Radulovacki MG, Carley DW. Proof of concept trial of dronabinol in obstructive sleep apnea. Front Psychiatry. 2013;4:1. doi:10.3389/fpsyt.2013.00001
- Carley DW, Prasad B, Reid KJ, et al. Pharmacotherapy of apnea by cannabimimetic enhancement, the pace clinical trial: effects of dronabinol in obstructive sleep apnea. Sleep. 2018;41(1):zsx184. doi:10.1093/sleep/zsx184
- Patel S, Hillard C. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther. 2006;318(1):304-311. doi:10.1124/jpet.106.101287
- Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245-259. doi:10.2147/tcrm.s1928
- Wentling N. Marijuana-PTSD study concludes after 10 years of planning, research. Stars and Stripes. March 31, 2019. Accessed October 25, 2021. https://bit.ly/3vQxQfp
- Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol. 2011;163(7):1411-1422. doi:10.1111/j.1476-5381.2010.01176.x
- Jones NA, Hill AJ, Smith I, et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther. 2010;332(2):569-577. doi:10.1124/jpet.109.159145
- Zuardi AW, Crippa JA, Hallak JE, et al. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des. 2012;18(32):5131-5140. doi:10.2174/138161212802884681
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- Fernández-Ruiz J, Sagredo O, Pazos MR, et al. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol. 2013;75(2):323-333. doi:10.1111/j.1365-2125.2012.04341.x
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