Introduction
Although cannabis remains illegal under federal law in the United States, 30 states and the District of Columbia have enacted medical marijuana (MM) laws, with cancer as a qualifying condition in all but one.
1 MM refers to the nonpharmaceutical cannabis products that health care providers may recommend for therapeutic purposes in compliance with state law, and therapeutic marijuana to nonpharmaceutical cannabis products used with medicinal intent, whether or not in compliance with state law. Medical marijuana comes in myriad strains, with differing potencies of active ingredients. It may be smoked, vaporized, ingested, taken sublingually, or applied topically.
To date, no randomized clinical trials of whole-plant MM have been conducted in oncology populations, leaving oncologists to extrapolate from research completed on pharmaceutical cannabinoids or to draw upon evidence gathered from patients with other diseases. Oral synthetic tetrahydrocannabinol (THC) has achieved US Food and Drug Administration approval for chemotherapy-induced nausea and vomiting, and a sublingual pharmaceutical cannabis extract has shown promise in the management of cancer pain. However, cannabis’ several hundred active ingredients, which include phytocannabinoids, phenols, and terpenes, work both synergistically and as inhibitors through “entourage effects.”
2-4 Therefore, comparisons between whole-plant MM and pharmaceutical cannabinoids that contain one or two active ingredients are speculative. In diseases other than cancer, eight small, short, randomized controlled trials reported that whole-plant cannabis possesses analgesic properties, and two observational studies have documented that MM laws are associated with statewide reductions in opioid-related hospitalizations and deaths; however, no randomized controlled trials have compared MM with standard pain regimens.
5-14 Support for other potential cancer-related uses for whole-plant cannabis (eg, nausea, vomiting, anorexia, cachexia) is based on lower-quality evidence.
3,4,15
Although three prior studies examined oncologists’ views on MM, all limited their inquiries to cannabis used as an antiemetic (despite many other potential oncologic indications) and all were completed before the passage of MM laws in the United States (and some were completed before the emergence of 5HT3 receptor blockers, now standard of care for chemotherapy-induced nausea and vomiting). In the first study (N = 2,430; response rate, 43%), nearly one-half of respondents reported that they would prescribe cannabis to some of their patients it is was if legalized.
16 A second study (N = 180; response rate, 78%) found that, combined, cannabis and pharmaceutical synthetic THC ranked ninth on a list of management strategies for chemotherapy-induced nausea and vomiting.
17 The third study (N = 2,430; response rate, 75%) indicated that only 1% of oncologists had recommended smoked marijuana to patients in the preceding 24 months.
18
To the best of our knowledge, there have been few scientific inquiries into the views of physicians practicing in the era of MM laws. A 2010 survey (N = 1,727; response rate, 30%) of family physicians practicing in Colorado demonstrated that only one-fifth of respondents believed physicians should recommend MM.
19 Less than one-third thought cannabis possesses significant health benefits, and well over one-half believed it carries significant health risks. Of note, those who endorsed making MM recommendations cited cancer and cachexia as frequent indications.
Given this background, we wondered whether the absence of data from randomized controlled trials testing MM’s efficacy for treatment of cancer-related symptoms would pose challenges for medical oncologists. We surveyed a nationally representative random sample of medical oncologists in the United States regarding their attitudes toward MM’s comparative efficacy and safety, their practices around clinical discussions regarding therapeutic cannabis, and whether they considered themselves adequately informed to make recommendations on the subject. We also explored factors associated with their beliefs and practices. We hypothesized that oncologists would report being insufficiently informed about MM, reticent to discuss or recommend therapeutic marijuana clinically, and skeptical about MM’s utility in cancer care given the limited evidence base.
Results
Medical Oncologists’ Characteristics
Of the 400 medical oncologists sampled, 24 were ineligible because they were retired, too ill, deceased, no longer practicing, not locatable, or away from practice for the study’s duration. Of the remaining 376 eligible medical oncologists, 237 completed a survey, yielding a raw response rate of 63.0%.
Among respondents, 65.8% were male, 57.9% were white, 36.0% completed oncology training ≥ 25 years ago, 52.8% held a medical school appointment, 52.8% practiced outside of a hospital setting, and 40.8% saw more than 60 patients per week (
Table 1). The largest proportion of respondents practiced in the South (32.6%) and 55.1% practiced in a state in which MM was legalized. Limited information was available on nonrespondents; however, sex and practice region did not differ significantly between respondents and nonrespondents.
Clinical Discussions, Recommendations, and Knowledge
Among respondents, 79.8% reported having discussed MM with patients or their families, and 45.9% reported recommending marijuana for cancer-related issues to at least one patient in the past year (
Fig 1). Oncologists practicing in the South were least likely to have discussed MM with patients or their families and those practicing in the West were most likely to have done so (68.9%
v 94.7%, respectively; bivariate
P = .014, multivariate
P = .02). Of those in the South, 34.7% had recommended MM compared with 84.2% in the West (
P < .001 in both bivariate and multivariate analyses). High practice volume (≥ 60 patients per week) was associated with an increased likelihood of an oncologist reporting having conducted MM discussions—88.9% versus 78.5% (40 to 59 patients per week) versus 69.6% (< 40 patients per week; bivariate
P = .01, multivariate
P = .006). Practicing outside a hospital setting was also associated with recommending MM (54.2%
v 35.0% of hospital-based oncologists; bivariate
P = .004, multivariate
P = .008; Appendix
Table A1, online only). Seventy-eight percent of the 186 oncologists who endorsed discussing MM with their patients reported that these conversations were more often initiated by the patients and their families than by the oncologist.
Slightly more than one-quarter (29.4%) of oncologists felt sufficiently knowledgeable to make recommendations regarding MM. Among the 45.9% who reported recommending marijuana clinically in the past year, 56.2% did not consider themselves to have sufficient knowledge to make a recommendation. In multivariate analyses, oncologists practicing in states with MM laws and those with high practice volumes (≥ 60 patients per week) were more likely to report feeling knowledgeable enough to make recommendations (both
P = .002; Appendix
Table A1).
Comparative Effectiveness of Medical Marijuana
Oncologists were divided in their perceptions of MM as an analgesic: 34.3% viewed MM as equal or more effective than standard pain treatments, 32.0% perceived it as less effective, and 33.8% reported they did not know. When asked whether MM is a useful adjunct to standard pain therapies, 66.7% responded “to a great extent” or “to some extent,” 23.7% responded “to a very little extent,” and 9.6% gave the response of “not at all” (
Fig 2). In multivariate analyses, oncologists who were < 15 years from their terminal degree were more likely than those > 25 years from their terminal degree to describe MM as equally or more effective than standard treatments for pain (42.0%
v 22.7%, respectively; bivariate
P = .03, multivariate
P = .047); the same was true for those practicing in nonhospital settings
v those practicing in hospital settings (39.5%
v 26.7%, respectively; bivariate
P = .048, multivariate
P = .049; Appendix
Table A2, online only).
Regarding poor appetite/cachexia, 64.5% of oncologists considered MM equally or more effective than standard treatments. For cancer-related nausea and vomiting, fewer than one-half (48.4%) reported MM to be equally or more effective than standard treatments. Oncologists’ perceptions of MM for other indications, relative to standard treatments, were similar: 45.8% indicated it was equally or more effective for anxiety; 40.3%, for general coping; and 34.9%, for poor sleep (
Fig 3). Oncologists also frequently responded, “I do not know,” although responses differed by condition (ranging from 27.6% for poor appetite/cachexia to 45.1% for poor sleep; Appendix
Table A3, online only).
Compared with other regions, oncologists practicing in the South were less likely, and those practicing in the West were more likely, to view MM as equally or more effective than standard treatments (eg, 54.1% v 94.7%, respectively, for poor appetite; bivariate P < .001, multivariate P = .005). Oncologists practicing outside of hospitals were more likely than hospital-based oncologists to view MM as equally or more effective than standard treatments for most indications (eg 54.8% v 32.4%, respectively for anxiety; bivariate P < .001, multivariate P = .001). Women were more likely than men to view MM as equally or more effective than standard treatments for nausea or vomiting (61.5% v 41.2%, respectively; bivariate P = .004, multivariate P = .014).
Risks of Medical Marijuana Versus Opioids
Most respondents viewed MM as presenting a lower risk than opioids for overdose death (74.8%) and addiction (51.5%); however, they perceived MM as presenting a comparable or higher risk than opioids for paranoia (51.7%) and confusion (51.1%;
Fig 4). These findings varied by sex and racial group (Appendix
Table A4, online only).
Discussion
To our knowledge, this study represents the first nationally representative investigation of medical oncologists’ attitudes, knowledge, and practices regarding MM since the advent of MM laws in the United States. Most respondents (80%) reported conducting discussions about MM with patients, and 46% reported recommending use of MM in the past year. These data highlight the salience of MM in today’s cancer care. However, our data also reveal concerning gaps in efficacy data and education; only 30% of oncologists reported feeling sufficiently knowledgeable to make MM recommendations, and more than one-half (56%) of those who made clinical recommendations considered themselves insufficiently knowledgeable to do so. Although our survey could not determine why oncologists recommend MM, it may be because they regard MM as an alternative therapy that is difficult to evaluate given sparse randomized controlled trial data. Alternatively, oncologists may have anecdotal experience with MM or respond to patient pressure in the face of a wave of state MM legalizations. Indeed, more than three-quarters of respondents reported that clinical conversations around MM are initiated by patients and their families more often than by the oncologists.
One focus of the study was the comparative effectiveness of MM as a treatment of cancer-related issues, including pain. Although our data demonstrate a lack of professional consensus regarding MM as a primary treatment of pain, more than two-thirds of respondents supported using MM as an adjunct to standard pain management strategies. These findings may reflect oncologists’ familiarity with the positive results of several small, randomized, placebo-controlled trials of MM for pain (although none in cancer populations, and none comparing MM to standard of care). These findings may also reflect the majority belief, identified in this study, that MM carries lower risk than opioids for addiction and overdose death.
Nearly two-thirds of oncologists reported that MM is equally or more effective than standard therapies for anorexia/cachexia. Given the lack of empirical evidence to support this assertion, the finding is surprising. It may reflect the extremely limited options available to treat anorexia/cachexia, or the fact that oncologists are extrapolating from their clinical experience with dronabinol, a synthetic THC pharmaceutical frequently used in oncology and approved by the US Food and Drug Administration for these indications.
4 Less surprising was that a large percentage of oncologists reported not knowing the comparative effectiveness of MM for cancer-related issues. This finding likely reflects a lack of empirical evidence regarding the therapeutic use of MM in general.
We observed significant differences in the attitudes and practices of oncologists based on nonclinical factors. For example, oncologists practicing in the South were more likely to hold negative views—and those practicing in the West, positive views—of MM’s comparative effectiveness. This finding may be due to MM’s status as a politicized health issue and regional sociopolitical differences.
22 Unfortunately, our data did not permit us to examine political party or religious affiliations. Similarly, hospital-based oncologists were less likely to recommend marijuana as therapy, compared with those practicing outside hospital systems. This finding may be due to hospital administrations’ reluctance to draft policies permitting health care providers to recommend MM (for fear of losing federal licensure).
23 Such findings deserve additional investigation.
Our study has several limitations, including a modest sample size, which can result in overestimates of effect sizes and low reproducibility of results, particularly for subgroup analyses. However, the sample size was sufficient to detect significant differences regarding several explanatory factors. As with all surveys, this study is vulnerable to nonresponse bias if nonrespondents differed systematically from respondents. However, we did not detect differences between respondents and nonrespondents based on sex or location of practice. Because of the nature of variable selection methods in general, other multivariable models may be plausible for some study outcomes. Finally, results are not generalizable to physicians in other specialties or those practicing in countries that have legalized MM on a federal level.
Despite these limitations, the study provides important national data on oncologists’ attitudes and practices regarding MM. Our data demonstrate that the vast majority of oncologists hold clinical discussions regarding MM and, generally, consider it a good augmentation strategy for cancer pain and equally or more effective than standard treatments for poor appetite/cachexia. Nearly one-half of oncologists have recommended medicinal use of marijuana, despite the study’s finding that a significant proportion do not feel sufficiently knowledgeable to make recommendations. Taken together, these findings identify a clinically problematic discrepancy between oncologists’ beliefs and practices and perceived knowledge regarding MM. They highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (eg, as an adjunctive pain management strategy or as a treatment of anorexia /cachexia) and the need for educational programs about MM, to inform oncologists who frequently confront questions regarding MM in daily practice.
4 Last, state and institutional policies are needed that incentivize trainings of clinicians on this important issue.