publication date: Nov. 6, 2020
Trials & Tribulations
By Dylan M. Zylla, MD, MS
Medical director, HealthPartners/Park Nicollet Cancer Research Center;
Adjunct assistant professor, University of Minnesota
In the election this week, voters said Yes to measures to legalize recreational cannabis (marijuana) in Arizona (60%), New Jersey (67%), and Montana (57%). Measures to legalize medical cannabis passed in Mississippi (68%) and South Dakota (54%).
Patients with advanced cancer battle debilitating symptoms of pain, nausea, and anxiety, among others. Many patients have grown fearful of taking opioids despite experiencing severe cancer-related pain, because of the ongoing opioid epidemic.
Cannabis (marijuana) use is becoming more prevalent in patients with cancer1, perhaps due to its ability to help manage multiple symptoms with minimal side effects.2,3 Despite scant clinical evidence, other than case reports, nearly one-quarter of patients also use cannabis, with the hopes it will treat their cancer.1
Furthermore, nearly three in four patients want information about cannabis from their cancer care team, yet only 15% receive it. However, only 30% of oncologists feel they have sufficient training to make informed recommendations about cannabis4, and 85% want more education.5
While robust randomized trial data does not exist with cannabis, since 2000, 19 clinical studies have assessed how cannabis containing products impact symptoms and global quality of life in patients with cancer.6 Nabiximols (an oromucosal spray containing a 1:1 ratio of delta-9-tetrahydrocannabinol (THC) to cannabidiol (CBD) was evaluated in two large placebo-controlled trials for cancer-related pain7, showing little overall impact in patients with refractory cancer-related pain.
In addition, two large survey studies involving over 4,000 patients demonstrated cannabis may improve a variety of symptoms, and may lessen use of concomitant medications such as opioids and antiemetics.2,3 The lack of clear dosing standards and delivery mechanisms make analyzing results across studies challenging.
For patients, the issues of safety, stigma, quality, and cost may be most important. Side effects of cannabis reported in the aforementioned studies were often mild. Cannabis may be safer than opioids as studies indicate lower opioid-related deaths in states that have enacted cannabis laws.
While cannabis has generally been considered safe with traditional cytotoxic agents, there is growing concern that the anti-inflammatory properties of cannabis may negatively impact immunotherapy.8,9 Furthermore, little is known about how cannabis may impact metabolism of oral chemotherapy (e.g., “targeted agents”), such as those commonly used for breast and prostate cancer.
The stigma of cannabis use may prevent more widespread implementation. Patients may be reluctant to disclose their cannabis use (or interest in potential use) for fear their oncologist may limit or alter the cancer-directed treatment plan. Determining the exact dose of THC or CBD patients are ingesting is difficult, unless laboratory testing of products becomes mainstream. Even less may be known about the ubiquitous over-the-counter CBD-only products where use is becoming widespread.
Finally, the costs of cannabis products can be prohibitive, with regular users paying $3,000 or more a year. In oncology, out-of-pocket costs for chemotherapy treatments and routine care already weigh heavily on patients.
In Minnesota, a randomized delayed-start trial of cannabis in patients with incurable cancer requiring opioids for pain was launched with a goal to minimize opioid requirements and improve quality of life.10 The study used a novel design utilizing a state-sponsored cannabis program with 36% of eligible patients screened ultimately enrolling. Of the 30 patients enrolled, cannabis users showed a trend toward improved pain control and lower opioid use.
Patients with advanced malignancies often prefer to focus on quality of life over quantity. As such, finding safe, effective, cost-efficient ways to help them manage symptoms is paramount. Barriers to conducting interventional cannabis research include:
requirement of a schedule 1 DEA license,
the myriad cannabis products/strains available, and
the lack of dedicated research funding opportunities.
In December 2020, the NCI Cannabis, Cannabinoids, and Cancer Research Symposium will bring together leaders in this field. Cannabis likely has a role, but determining which patients (and symptoms) benefit the most is currently challenging.
High-quality studies are needed to enable patients, providers and policymakers to make informed decisions on the use of cannabis. Without additional data, the true benefits and risks of cannabis use will remain clouded in smoke.
Pergam, S.A., et al., Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer, 2017. 123(22): p. 4488-4497.
Bar-Lev Schleider, L., et al., Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer. Eur J Intern Med, 2018. 49: p. 37-43.
Braun, I.M., et al., Medical Oncologists’ Beliefs, Practices, and Knowledge Regarding Marijuana Used Therapeutically: A Nationally Representative Survey Study. J Clin Oncol, 2018. 36(19): p. 1957-1962.
Zylla, D., et al., Oncology Clinicians and the Minnesota Medical Cannabis Program: A Survey on Medical Cannabis Practice Patterns, Barriers to Enrollment, and Educational Needs. Cannabis Cannabinoid Res, 2018. 3(1): p. 195-202.
Steele, G., T. Arneson, and D. Zylla, A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety. Curr Oncol Rep, 2019. 21(1): p. 10.
Fallon, M.T., et al., Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies. Br J Pain, 2017. 11(3): p. 119-133.
Bar-Sela, G., et al., Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome. Cancers (Basel), 2020. 12(9).
Taha, T., et al., Cannabis Impacts Tumor Response Rate to Nivolumab in Patients with Advanced Malignancies. Oncologist, 2019. 24(4): p. 549-554.
Zylla, D., et al., A randomized trial of medical cannabis (MC) in patients with advanced cancer (AC) to assess impact on opioid use and cancer-related symptoms. https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.31_suppl.109, 2019.
The electorates in four states, New Jersey, South Dakota, Montana and Arizona, voted decisively to legalize recreational marijuana Nov. 3, 2020, and voters in Mississippi and South Dakota also approved initiatives to legalize medicinal marijuana. In Oregon, voters decriminalized small amounts of heroin, cocaine, and methamphetamine—becoming the first state to do so. In Washington, D.C., voters approved a ballot initiative to decriminalize psychedelic mushrooms, among other psychedelic plants.