The results from our survey revealed the willingness to participate in and advocacy for proceeding with 2 NCI research proposals exploring cannabis use in patients with cancer. The 58% response rate signals awareness and interest in cannabis use in front-line care team providers in our cancer practices. These observations, for the most part, align with a published survey of the Society of Cannabis Clinicians, a group that would be considered experienced and knowledgeable in prescribing and counseling their patients on cannabis use. ¹⁸ In this survey, 133 participants were assessed for eligibility, and 45 physician surveys were analyzed for a response rate of 34%. ¹⁸ The major discrepancy between their and our survey is that in their survey, 78% (29/37) of physician responses to a specific knowledge survey question considered themselves knowledgeable about cannabinoids and the endocannabinoid system, whereas in our survey, only 15% considered themselves knowledgeable. Also, only 13% of front-line providers in our survey referred patients to a physician or provider who was knowledgeable and known to prescribe medical cannabis.

As the prevalence of cannabis use increases in contemporary cancer practice, providers must become better informed about its use and safety profile, provide instruction and education during the formative years of oncology training, and help patients to feel comfortable disclosing and discussing use with their care teams. ^{11–13,16,19} A recently published, large retrospective case series in 3148 Australian patients using medical cannabis echo these thoughts. ²⁰ Findings from this study suggest sustained benefits in health-related quality of life. However, and importantly, adverse events were common but rarely severe. ²⁰ Recent clinical guidance from the American Society of Clinical Oncology and policy statements from the American College of Physicians advocate for more prospective clinical research, training, and efforts to address challenges with current federal and often conflicting state legislative frameworks. ^21,22 NCI also advocates for advancing research in this area, given the paucity of well-designed prospective clinical studies exploring the benefits and harms of cannabis use. ^23,24 Undoubtedly, hurdles persist, but chief among those regarded by the National Institute on Drug Abuse, NIH, US Food and Drug Administration (FDA), and researchers include the US regulatory status of cannabis and cannabinoids, sources for cannabis and cannabinoid study medications, and limited funding and resources to support studies. ²⁴ After the release of RFA-CA-22-052, the NCI awarded 5 highly coordinated, longitudinal cohort studies in patients with newly diagnosed cancer to explore the benefits and harms of cannabis in thousands of patients under a cooperative U01-funding mechanism. These studies are summarized in Table 3 and have all been launched.

Maine is a small state (population of 1.38 million), is the most rural state (61.4% of the population resides in rural areas per the Health Resources and Services Administration criteria), and has the oldest population in the nation (median age of 44.8 years, 6 years older than the national median). ^25–28 Given this profile, and Maine’s permissive legislative posture toward medicinal and recreational cannabis use and vibrant cannabis industry, the state is an ideal clinical laboratory to pursue research in this evolving therapeutic area. MHCCN investigators are participating in Wake Forest’s U01-supported Complementary Options for Symptom Management in Cancer (COSMIC) study (WF-2304-A1724014) as a rural site champion. ²⁹ This joint Wake Forest NCORP Research Base and Alliance–led study aims to recruit 2000 patients with newly diagnosed breast, non-small cell lung, and colorectal cancer; melanoma; and non-Hodgkin lymphoma. These patients will be followed over 12 months. Patients will be recruited in 2 cohorts during cancer treatment: those using and not using cannabis in the context of pursuing other complementary therapies during treatment. Surveys documenting cannabis use, and the benefits and harms of use on cancer and treatment-related symptoms, will be collected. A subset of patients with lung cancer will participate in pharmacokinetic and pharmacodynamic correlative studies exploring drug-drug interactions and immunosuppressive effects of cannabis.

Our team developed a companion study to the COSMIC study, supported by a Wake Forest NCORP Research Base supplemental award. We launched an investigator-initiated study (COSMIC Releaf^™, MH IRB# 2278577) in 45 patients with cancer who use cannabis. ³⁰ Eligible patients are either (1) undergoing active treatment, including surgery, radiation, and systemic therapy as a single or combined modality therapy; or (2) in active follow-up after treatment or at any point along the survivorship spectrum. We focused on a stated objective outlined in RFA-CA-22-052 to document the precise product and drug content among patients that use cannabis, with the understanding that usually patients and providers do not know this information at the time of acquiring a drug/product and/or subsequent use. With this goal in mind, we are using a customizable, protocol-specific patient application, Releaf App^™ (MoreBetter Ltd., Hyattsville, MD), that is suited for iPhone or Android platforms and supports journal entries to record cannabis use and the type of product. This application has been used by more than 18123 study participants across numerous studies and in a current FDA-sponsored study. ^31–40 As part of the study start-up, we will work with the Releaf App to verify the product inventory at Maine cannabis storefronts’ [both medical-use and adult-use (recreation) stores] in the app. Thus, for participants, data on the type of cannabis and/or cannabinoid product, composition (eg, THC and CBD/CBG/CBN), and frequency of use will be directly captured in the app and linked to the storefront at the time of purchase. There are 2 project-specific electronic data capture systems for this project: REDCap and Penzai (US patent pending). Penzai is a web-based software application (MoreBetter, Ltd., Hyattsville, MD) that permits customizable, decentralized, and remote data collection. This software can also send (via text or email) reminders to participants on a pre-arranged schedule to prompt journaling of cannabis consumption in the Releaf App, which is highly suited to our study. These reminders will be sent weekly with formal monthly check-ins over 6 months of study follow-up. Nearly two-thirds of respondents in our survey valued learning more about cannabis use for patients’ symptoms management. Given this finding, the 2 studies we are participating in provide an excellent departure point to further expand on this opportunity. Our approach is innovative, and in this manner, we have every expectation to precisely capture the benefits and harms along with the cannabis product and content.

As we embarked on this study, we worked closely with our IRB on several aspects of our study and design. Chief among them is to ensure confidentiality and privacy of participants given the current legal environment regarding cannabis use. Two themes emerged. First, to protect patient confidentiality, we have been granted a waiver of documentation of written consent. The patient will be given an IRB-approved informed consent document to review with the study coordinator, who will document verbal consent and sign the form. The patient will retain this copy of the consent document, which will only include their study identification number. This arrangement avoids a signed consent document linking a patient to the study. A second theme is to make study participation agnostic to the electronic health record and, thus, ensure patient privacy regarding professional, employment, health insurance, or personal concerns. To accommodate data management, we will use 2 REDCap databases. One database will act as the master key database that holds protected health information and manages small stipends that have been incorporated into our study design to facilitate study participation. The other will hold study data. The master key database will be deleted at the end of the study. We have adopted these safeguards to enhance patients’ willingness to participate in our study. These steps are additional considerations we believe are important to address the inherent barriers in cannabis-related clinical study.

It is important to acknowledge that our survey was extended to approximately 50% of MHCCN care team members (n = 171) among more than 350 providers. This subset is most likely to engage in discussions with their patients about cannabis use that otherwise are unlikely with primary care physicians, radiologists, and pathologists, among others. This subset could be considered a limitation of our study. Furthermore, the response rate of 58% is robust for this type of survey and representative of MHCCN practice locations and front-line providers. Upon perusal of Tables 1 and 4, the response rate corresponds to the analytic tumor volume at each MHCCN practice, with one exception. The 2% response rate at the Harold Alfond Center for Cancer Care (Maine General Medical Center) does not correspond to the 17% analytic volume that this location contributes to the network. In short, there is good representation of provider input across metropolitan, micropolitan, and rural practices that adds value.

Lastly, 3 important themes from our survey provide opportunities for future care team learnings and engagement. Notably, only 15% of respondents are knowledgeable in cannabinoids and the endocannabinoid system, so there is considerable opportunity for providing educational platforms for our providers, especially given the growing prevalence of cannabis use by patients with cancer. ^19,21,22 Similarly, it is important to incorporate instruction in our hematology/oncology fellowship program that is a gap nationally. ¹⁶ And although there is integrative medicine and cannabis expertise locally, referral channels can be enhanced to capitalize on this resource.