Cannabis for Oncology Patients: A Clinical Review

As the country continues its spirited conversation about expanding the legal use of cannabis, oncology practitioners have their eye on another issue: the role of marijuana in helping patients to manage the often debilitating symptoms that follow a cancer diagnosis.

Cannabis use goes back 3000 years to China, followed by a long and uneven history of ceremonial, recreational, and medicinal applications. Anecdotally, cannabis effectiveness is reported for a wide range of illnesses— including arthritis, chronic pain, fibromyalgia, glaucoma, multiple sclerosis, cancer, nausea, asthma, anxiety, depression, epilepsy, glaucoma, alcohol withdrawal, and infection^1,2; however, seminal evidence is lacking to support cannabis as a reliable treatment.

More than half of the states in the United States have legalized some form of medical-use cannabis and more states are expected to join those ranks.³ This November, California is among several states to vote on cannabis legalization for recreational use; if the ballot measure passes there, momentum generated from that big state will build, likely prompting more states to consider legalization.

Sixteen states have enacted laws allowing the use of cannabis formulations that are low in the tetrahydrocannabinol (THC) associated with its psychological high, but high in cannabidiol (CBD), the compound believed to target various medical ailments and symptoms.⁴ More than 1700 strains of cannabis are currently available for purchase from authorized dispensaries. The delivery systems for administration are extensive, including smoking, vaping, edible foods and oils, tinctures, juices, teas, and salves.^3,5

Political, economic, and medical interests want further clinical investigations into the pharmacology of cannabis and its efficacy in relieving various symptom and antitumor properties.^4,6 In August, some restrictions on growing cannabis for research lifted, and now federally authorized researchers and drug companies may use cannabis grown in places other than its well-secured facility at the University of Mississippi.

Why the change? The Drug Enforcement Administration announced: “Under the new approach, should the state of scientific knowledge advance in the future such that a marijuanaderived drug is shown to be safe and effective for medical use, pharmaceutical firms will have a legal means of producing such drugs in the United States—independent of the [federal government] contracting process.”⁷

Cannabis Use for Oncology Patients

In the United States, cannabis is classified as a Schedule I drug due to what the government considers its high potential for abuse. Although efforts continue to change its classification, the FDA announced in August that the classification will not change, thus continuing to limit vigorous, targeted research that would expose cannabis’ potential as a treatment for many medical conditions.^3,8

In daily practice, however, patients continue to ask their providers about using cannabis and finding ways to obtain it. And more and more, healthcare providers recommend cannabis as a promising strategy for oncology-related symptom management (Box: Provider Guidelines).

Provider Guidelines^1,5,8

• Establish a treatment plan, based on patient history and physical.

• Consider if standard symptom management treatments are not working or have been exhausted.

• Prescribe to adults only (no prescribing to children or adolescents).

• Avoid prescribing if history of psychiatric disorders or known family history of psychiatric disorders.

• Address any interactions, eg, with dronabinol, since it is formulated with sesame oil and can pose a risk of anaphylaxis to those with a hypersensitivity to sesame seeds or nuts. Other contraindications to cannabinoid use include a history of seizures, and concurrent use of alcohol, sedatives, hypnotics, or other psychoactive agents. Patients taking cannabinoids should be advised not to drive.

• Individualize the dosing/titration plan, taking into account symptom relief and adverse effects.

• Recommend obtaining from a licensed dispensary operated under quality control guidelines and regulations.

• Regular follow-up and monitoring by providers, with accurate documentation.

• Base recommendations on updated, growing body of literature and evidencebased, rigorous clinical studies.

Nevertheless, providers may make cannabis recommendations with very little known about potential adverse effects, drug interactions, optimal dosing and administration, and overall strategies for tolerance and effectiveness.³

Side effects—thought to be dose- or patient age- related—can be both physiologic (hypotension with reflex tachycardia, gastroparesis, ataxia, somnolence, dry mouth), and psychologic (euphoria, poor concentration), and, at high doses, anxiety, delusions, and hallucinations.

Based on anecdotal reports, tolerance for many of these effects develops over 1 to 2 weeks.⁹ Although many cellular and molecular studies provide strong evidence that inhaled marijuana is carcinogenic, the epidemiologic evidence of a link between marijuana use and cancer is still inconclusive.³

It’s not surprising, then, that significant concerns remain about recommending cannabis among practitioners:

“My biggest concerns with medical marijuana is that because of the lack of studies, we do not know if there are significant contraindications that might influence oncology treatment and potential drug-drug interactions that should be considered,” according to Arlene Cramer FNP, AHPCN, from UC San Diego’s Doris A Howell Palliative Care Service.

In addition, she continued, “Medical marijuana is expensive. Obtaining the prescription and medical marijuana care are out-of-pocket expenses, as is the actual purchase of the marijuana. Cost is a major obstacle to our poorer clients, and I fear that they may resort to illegal and less safe sources to purchase these products.”

Managing Side Effects With Marijuana

What is known at this point is that cancer-related cannabinoids are used with some effectiveness as an adjuvant pain management strategy, as an antinausea/vomiting agent for patients undergoing chemotherapy, and as an appetite stimulant to offset cancer-related weight loss. In addition, providers see anecdotal benefits when patients use cannabis as a sleep aid and to reduce anxiety.^3,5,10

In 2015, the Journal of the American Medical Association published a meta-analysis of 79 randomized trials covering more than 6400 participants, finding moderate-quality evidence to support the use of cannabinoids for treating chronic pain. Additional analyses concluded that some low-quality evidence exists suggesting that cannabinoids could impact nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.¹¹

It is suggested that cannabinoids may act synergistically with opioid analgesics in managing cancer-related pain. In the treatment of HIV-related peripheral neuropathy, data show that cannabinoids may be effective in the treatment of neuropathic symptoms that patients experience due to disease, chemotherapies, and diabetes-associated comorbidities.^8,12

As an antiemetic cannabinoid agent, dronabinol and nabilone are FDA-approved for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond to conventional antiemetics. The FDA approved a new oral solution formulation of dronabinol (Syndros) in July for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients who have not responded to conventional antiemetic therapies.

However, cannabinoids for this use may prompt potent side effects (ie, anxiety, paranoia, agitation) and may only be effective for a short time.^4,13 And for most patients, 5-HT3 receptor antagonists and NK-1 receptor antagonist agents—now prescribed as standard therapies—have been shown to be effective and well tolerated to treat CINV, thus lessening the urgency to study cannabinoid as an antiemetic agent.²

Case Study

TS, a 50-year-old female patient, is receiving ongoing care from medical oncology and palliative care teams for metastatic colorectal cancer (pT4zN1bM1 with positive margins). The patient was first diagnosed in January 2014 and presented with abdominal pain. Treatment included colostomy, 4 cycles of FOLFOX, liver resection, and bilateral ureteral stent placement. The patient currently has stable disease and is being treated with FOLFIRI every 2 weeks. Most recent issues:

• Urinary tract infection, treated with macrobid, pyridium

• Cancer-related pain/neuropathic pain, radiating from abdomen to back, treated with fentanyl patch (100 mcg/hour, changed every 72 hours), hydromorphone (8-12 mg/day), and acetaminophen (as needed).

• Refractory nausea: better symptom control now, treated with olanzapine and cannabis (edible).

TS reports that cannabis has reduced her nausea related to chemotherapy and increased her appetite so that she “feels better” since starting cannabis 2 months ago, and her weight gain = 2 lbs: “I was reluctant to use (cannabis) at first...probably because of the way I was raised. But it has been a positive experience.” The patient takes cannabis daily (dosing recommended via Rick Simpson Oil method; http://bit.ly/2c55yG2). She prefers oil or chocolate (edibles) and orders her cannabis online for home delivery from an approved medical dispensary.

As an appetite stimulant, dronabinol is FDA approved for the treatment of anorexia-associated with weight loss in patients with HIV/AIDS; however, it is not clear whether this effect may stimulate calorie intake or enables fat/water accumulation rather than add lean body mass.²

Once again, enough evidence supporting the use of cannabinoids for cancer-associated anorexia has not been allowed to build,² despite the fact that some patients report advantages (Case Study).

Looking Ahead

A recent Gallup poll estimates that 33 million or 13% of US adults use cannabis, suggesting a doubling of use in the past 3 years.¹⁴ This tsunami of interest in cannabis and its use only underscores the need to establish ongoing clinical trials to show just what cannabis can or cannot offer to oncology patients.

“In the past decade or so, we are starting to see that marijuana for medical use has reemerged,” according to Tim Byers, MD, MPH, professor, University of Colorado, and Director of the Center for Public Health Practice, Colorado School of Public Health.

“Marijuana is not a new drug; it is centuries old. And, it has a mixed story illustrating that it has medicinal effects and also recreational and drug abuse effects.”

Thus far, the bulk of the cutting-edge research into the clinical use of cannabis for oncology patients is taking place outside of the United States. For example, in Canada and Israel—where medicinal use has already been legalized—studies are determining the potential effect that cannabis has on cognitive impairment in patients undergoing chemotherapy.

Other studies are evaluating the structure of cannaboid compounds, the efficacy of smoked cannabis for pain relief in patients undergoing radiation therapy for lung cancer, dronabinol’s effects on appetite stimulation and chemosensory abnormalities such as taste and smell, CBD and THC effectiveness in varying ratios, and cannabinoid compounds as adjuvant chemotherapy.^3,4

Nevertheless, as Byers points out, to advance cannabis medicinal use in the United States requires a foundation of research that can only take place if so many legal restrictions are lifted:

“We need to fix the legislation about federal restrictions and policies about research, so we can really study what works and doesn’t work in patients with cancer.”

States Where Medical Marijuana Is Legal Twenty-five states and the District of Columbia have following states have passed laws to legalize medical marijuana:

Alaska

Arizona

California

Colorado

Connecticut

Washington, DC

Delaware Hawaii

Illinois

Louisiana

Maine

Maryland

Massachusetts

Michigan

Montana

Nevada

New Hampshire

New Jersey

New Mexico

New York

Ohio

Oregon

Pennsylvania

Rhode Island

Vermont

Washington

Source: ProCon.org. Medical Marijuana.

Cannabis—Definitions of Terms^5,8,12

Cannabinoids—the biologically active compounds from the cannabis plant. The plant contains about 400 compounds derived from its secondary metabolism, many of which may contribute to its medicinal effect.

Cannabis (marijuana)—cannabis sativa plant that is bred for its potent, resinous glands (trichomes). These trichomes contain high amounts of delta-9 tetrahydrocannabinol (THC), the cannabinoid most known for its psychoactive properties (marijuana “high”). THC mimics compounds in the body called endogenous cannabinoids (elements of the endocannabinoid system). Other cannabis compounds affect the nervous system and have neurologic effects (eg, pain, seizures)

Hemp—from the cannabis sativa plant (bred for industrial use—oils, topical ointments, construction, clothing). Hemp contains only trace amounts of THC.

Cannabidiol (CBD)—one of at least 113 active cannabinoids identified in cannabis. It is a major phytocannabinoid, accounting for up to 40% of the plant's extract. CBD is considered to have a wide scope of potential medical applications, including relief of pain, nausea and inflammation.

Dronabinol—a synthetic pill form of delta-9-THC, the main ingredient in Schedule III drug Marinol; dronabinol was approved in 1985 by the FDA as an antiemetic for patients treated with cancer chemotherapy. In July 2016, the agency approved a liquid version (dronabinol oral solution; Syndros) to treat chemotherapy-induced nausea and vomiting in patients who have not responded to conventional antiemetic therapies and for treating anorexia associated with weight loss in patients with AIDS.

Nabilone—is an engineered THC analog that forms the basis of the Schedule II drug Cesamet. It is approved by the FDA as a secondary option for treatment of nausea and vomiting associated with cancer chemotherapy, when standard treatment is not effective.

Schedule I Drugs—a Drug Enforcement Administration (DEA) term, referring to the Controlled Substances Act. Schedule I drugs are not accepted for medical use and considered high in potential for abuse. Other Schedule I substances include heroin, LSD, mescaline, methylqualone, and gammahydroxybutyrate (GHB). In August 2016, the DEA re-reviewed the classification but ruled that cannabis’ Schedule I classification should remain in effect.

Ellen Carr, RN, MSN, AOCN, is a clinical educator at the Moores UCSD (University of California, San Diego) Cancer Center in La Jolla. She has been a healthcare writer for the past 30 years, specializing in clinical oncology nursing, therapeutic and diagnostic technologies, and patient advocacy.

Reference

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2. Wilner L, Arnold R. Fast Facts Concepts #93: Cannabinoids in the treatment of symptoms in cancer and AIDS. Palliative Care Network of Wisconsin. www.mypcnow.org/ fast-facts. Updated June 2015. Accessed August 3, 2016.

3. National Cancer Institute. PDQ Cannabis and Cannabinoids. Updated May 2016. www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq. Accessed August 3, 2016.

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11. Whiting P, Wolff R, Despande, S., et al. Medicinal use of cannabinoids. JAMA. 2015;313(24):2456-2473.

12. Abrams D, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther. 2015;97(6):575-86.

13. Schrot R, Hubbard J. Cannabinoids: Medical implications. Ann Med. 2016;48(3):128-141.

14. McCarthy J. One in Eight US Adults Say They Smoke Marijuana. www.gallup.com/poll/194195/ adults-say-smoke-marijuana.aspx [Updated August 8, 2016]. Accessed August 14, 2016.