Medical Marijuana Use in a Community Cancer Center

According to the American Cancer Society, nearly 1.7 million people will be diagnosed with cancer in 2018, and an estimated 609,000 people will die as a result of this disease in 2018.¹ Although cancer prevention, detection, and treatment have markedly improved survival rates among patients with cancer, cancer treatment still causes many adverse effects. Numerous prescription medications are used to help alleviate the unwanted adverse effects of these agents, but some patients may be turning to more alternative remedies, such as marijuana. Some patients use marijuana to help manage a variety of symptoms, whereas others claim that they use it to treat their cancers. Marijuana is currently the most popular illicit drug in the United States.^2,3 According to a recent survey, 89.5% of adults who use marijuana use it for recreational purposes; 10.5%, for medical purposes; and 36.1%, for mixed medical/recreational use.^2-4 Many states, including Michigan, have legalized marijuana for medical purposes. There are currently 10 qualifying conditions in the state of Michigan in which patients may use marijuana for medical purposes, including cancer and associated symptoms.⁵

Patients who are undergoing treatment for cancer may use marijuana to manage symptoms such as severe nausea, chronic pain, anxiety, and/or cachexia/anorexia. According to a recent report, evidence suggests that oral cannabinoids are effective antiemetics in the treatment of chemotherapy-induced nausea and vomiting and chronic pain.² There is no or insufficient evidence, however, that cannabis or cannabinoids are an effective treatment of cancer-associated anorexia-cachexia syndrome or anorexia nervosa.²

Anecdotally, patients have reported use of marijuana to treat their underlying cancers.^2,6 Currently, there is no or insufficient evidence that marijuana is an effective treatment for cancer.² Although there are limited in vivo and in vitro studies, there has been only one small phase I study (N = 9 patients) in which patients with glioblastoma multiforme were given tetrahydrocannabinol by intracranial adminsitration.⁷

Numerous adverse effects are associated with the use of marijuana, including cardiovascular, respiratory, CNS, and potential carcinogenic effects. Current evidence suggests that smoking cannabis does not increase the risk for some cancers, such as lung and head and neck, but has modest (limited) evidence for the development of non–seminoma-type testicular germ cell tumors.² Drug-drug interactions exist with marijuana, especially when administered with medications that act on the CNS, such as tricyclic antidepressants, opioids, and antipsychotic medications.⁸ Drug-disease interactions also may exist with concurrent use of marijuana; examples include immunosuppressive disorders, psychiatric disorders, cardiovascular disease, respiratory disease, diabetes and obesity, and pregnancy.^2,8-10

In 2017, our community-based outpatient cancer center encountered approximately 14,743 patient visits by six hematologists/oncologists and 727 chemotherapy infusions. It is believed that patients who were undergoing chemotherapy treatment in our cancer center were using marijuana for symptom management and/or as an additional option to treat their cancers. It is not currently known how many patients are using marijuana for these indications. The primary purpose of this study was to compare the incidence of marijuana use in patients with early- versus advanced-stage cancers. Other outcomes included comparisons of the differences in adverse effects, drug-drug interactions, and drug-disease interactions in patients who use marijuana versus those who do not use marijuana.

Throughout the study period, 229 patients met the inclusion criteria and were invited to participate in the survey. Of those 229 patients, 51 patients declined, and three were excluded after they took the survey; 175 patients remained for the final analysis (Fig 1). Patient demographics are listed in Table 1. Of note, 56 patients (32%) had early-stage cancers, and 119 (68%) had advanced-stage cancers.

In general, the medical and recreational uses of marijuana have been well quantified by several organizations.^4,14-16 We expect the numbers of users to continue to increase as more states approve both the medicinal and recreational uses of this schedule I controlled substance. Distribution centers and dispensaries will continue to grow as well. To our knowledge, little is known about the incidence of marijuana use specifically in the population of patients with cancer. In our community-based cancer center, patients and health care providers often inquire about marijuana and about how to get certified for medicinal use. We did not know, however, how many patients were actually using marijuana; therefore, we developed a questionnaire to determine the overall incidence of marijuana use. In our cancer center, we found that 18.3%, or approximately one in five patients with cancer who were undergoing chemotherapy treatment, were using marijuana. The majority of these patients were using marijuana for symptom control, which may explain why a difference was not seen between early- and advanced-stage cancer groups, because both groups were receiving chemotherapy. Only four patients indicated that marijuana was being used for cancer treatment, although no randomized clinical studies in patients with cancer support this indication at this time. It is unclear whether cannabinoids promote tumor growth and proliferation or possess antitumor properties, so more research is needed.¹⁷ In a recently published survey of cannabis use at a large comprehensive cancer center in a state where cannabis is legal recreationally and medically, the authors reported a 24% incidence of use, which was slightly higher than our findings.⁶ Active cannabis use was defined as use within the last year (compared with use within the last month in our survey). Similar to our findings, the majority of patients used marijuana for pain, nausea/vomiting, appetite, and stress. Also, a small number of patients (7.3%) used marijuana for recreational purposes (compared with five responses of nonmedical reasons for use in our survey). It should be noted that, in our survey, patients could provide more than one indication for use. It is unclear from these results whether recreational use would affect use in patients with cancer.

According to our survey, most patients used marijuana through a variety of routes of administration, on a daily basis, and with a frequency of 5 to 7 days per week. More patients who used marijuana reported pain, nausea, appetite issues, and anxiety compared with those who did not use marijuana. It is not known if these patients inherently had higher baseline scores for these symptoms and sought out marijuana use for better symptom management or if it could be argued that marijuana did not help these particular patients better control these symptoms. Statistical and clinical significance could not be determined from this study. Also, we did not correlate the route of marijuana administration to symptom indication. The bioavailability and half-life of marijuana may differ according to whether the patient inhales or ingests the product.¹⁷ Surprisingly, no difference was noted between nonusers and users in terms of tiredness or drowsiness, an expected adverse effect associated with marijuana use. It is not known, however, what time of day marijuana was used and whether this would have affected patient adverse effects or not.

There is limited information about interactions between marijuana and other drugs. US Food and Drug Administration–approved cannabinoid preparations appear to interact with a variety of drugs, and information is often extrapolated from these reports.⁸ Delta(9)-THC is metabolized by CYP3A4 and CYP2D6 to an active metabolite, 11-hydroxy-THC.^17,18 Some cannabinoids may interfere with the P450 isoforms CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Little to no information is available about interactions between marijuana and chemotherapeutic medications. One study indicated no pharmacokinetic alterations when irinotecan or docetaxel was given concurrently with cannabis tea.¹⁹ It is also unclear whether cannabinoids may be immunostimulating or immunosuppressive and how this may affect response to programmed death ligand 1 (PD-L1) inhibitors (ie, either improvement or impairment of immunity and clinical response).^17,18 Many patients with cancer are prescribed benzodiazepines, opioids, muscle relaxants, antidepressants, and antiemetic medications (eg, prochlorperazine), all of which can potentiate the CNS depressant effects of marijuana when they are used concurrently. Our study results most commonly reflect these CNS interactions, especially in patients who reported marijuana use. Alcohol consumption and marijuana use should be assessed, and patients should be educated about the impact of marijuana used concurrently with CNS depressants.

Some other risks associated with marijuana use include the impact of this agent on patient comorbidities. There is some evidence that marijuana use may trigger an acute myocardial infarction, ischemic stroke, or subarachnoid hemorrhage, and increase the risk of prediabetes.^2,8 Those with pre-existing respiratory conditions may experience worsening of symptoms with use and improvement upon cessation of marijuana smoking. Marijuana use has been associated with an increased development of schizophrenia and psychoses and symptoms of mania and hypomania. An increased risk of the following conditions has also been documented: depressive disorders; suicidal ideation, attempts, and completion; and social anxiety disorder. Impairments in learning, memory, and attention have been reported.^2,20,21 Cardiovascular disease was the most common comorbidity considered to be potentially exacerbated by marijuana use in our patients studied.

According to our results, the majority of patients are using marijuana on their own accord without the advice of or consultation with a health care provider, as evidenced by the lack of certification with the state of Michigan and a lack of counseling on the benefits, harms, or drug- or disease-marijuana interactions. In our survey, we did not ascertain why patients did not obtain certification, nor did we address knowledge or attitudes of the oncologists. Patients may be fearful of judgement, being labeled drug users, losing their privacy, being turned in to the authorities (especially if they are not certified), or being rejected by their providers. Health care providers may be reluctant to certify a patient because of the lack of scientific evidence of efficacy, lack of formulation standards (dose, potency, route), abuse potential, adverse effects/harms, lack of institutional policies, availability of other US Food and Drug Administration–approved medications, and schedule I controlled substance designation of marijuana (despite legality at the individual state level).^22-26 In a recently published survey, providers who were eligible to certify children had less favorable attitudes toward marijuana and were less amenable to use in early-stage cancer.²⁷ It was proposed that those eligible to certify may have more at jeopardy in terms of licensure and/or clinical or legal ramifications.

Information and education for patients with cancer who are interested in pursuing medical marijuana use should ideally be received from their cancer care providers. Key components of marijuana education should include the following: importance of certification within the respective state; clinical benefits (positive and negative) for symptom management; lack of evidence for cancer treatment; potential harms associated with marijuana (eg, exacerbation of certain disease conditions, effect on cognition, potential for increased risk of developing certain cancers, adverse effects, risks in pregnancy to the fetus, significant risk of motor vehicle accidents, addiction potential, and contaminant risks from pesticides and aspergillosis); potential for drug interactions; and proper storage, handling, and disposal.^10,17,28 A medicinal cannabis treatment agreement has been suggested by some.²⁹

In conclusion, the use of marijuana in one in five patients with cancer in our community-based cancer center is a large enough number of patients, we believe, to warrant additional intervention. Our patients are using marijuana for a variety of indications, irrespective of cancer stage. As a result of these findings, we plan to develop a position statement about appropriate indications of marijuana use in our patient population, to develop educational materials that will better inform patients of the risks and any potential benefits associated with marijuana use, and to screen for potential drug-drug and drug-disease interactions.

Supported by the Ferris State University Office of Research and Sponsored Programs. Presented at Herbert Herman Cancer Center Oncology Grand Rounds, December 15, 2017, Lansing, MI. The views expressed within are those of the authors and not of the institutions or funder.