A Primer on Rising Medical Cannabis Use in Oncology

Eloise Theisen, MSN, AGPCNP-BC

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. As of October 2021, 36 states along with the District of Columbia have legalized medical cannabis, and 19 states plus the District of Columbia have legalized adult-use cannabis.¹

Furthermore, 7 states are expected to have adult-use cannabis legislation on the ballot in 2021, which could mean more than half of the United States supports adult use. In addition to increased cannabis legalization, there has been an explosion of cannabidiol and other nonimpairing 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 1 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:

• Conclusive evidence suggests that cannabis or cannabinoids are effective at treating chronic pain in adults with chemotherapy-induced nausea and vomiting.
• 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.
• There is insufficient evidence to demonstrate whether cannabis or cannabinoids are effective or ineffective in treating patients with gliomas or cancer-associated anorexia-cachexia syndrome.

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 cancerrelated 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 the 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

Cannabinoids are defined as chemical compounds, which can either 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 conditions^7-18:

• Nausea
• Pain
• Appetite loss
• Insomnia
• Sleep apnea
• Anxiety
• Inflammation
• 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 conditions^19-24:

• Nausea and vomiting
• Seizure disorders
• Psychosis disorders
• Inflammatory disorders
• Neurogenerative disorders
• Depression

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

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

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

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.

Ingestion

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. Due to 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 of the unwanted AEs associated with cannabis overconsumption.

Drug Interactions

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 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.

Dosing

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 real-world 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 all a patient needs to achieve 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.

Eloise Theisen, MSN, AGPCNP-BC, is a board-certified adult geriatric nurse practitioner who specializes in cannabis therapy and is cofounder and chief executive officer of Radicle Health and the Radicle Health Clinician Network.

References

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