Andrew Winkler, MD, associate professor of otolaryngology and director of facial plastic and reconstructive surgery at the University of Colorado, Denver, works in one of the first two states to legalize recreational marijuana and has done research to investigate links between marijuana legalization and facial trauma. But, when patients ask him questions about medical marijuana use, including the ubiquitous cannabidiol (CBD) oil, he often feels ill-equipped to respond.
“It’s a tricky thing,” he said. “It’s a difficult position. We get asked by our patients—not a lot, but on occasion—about using these medications to treat pain and just recreationally around times of surgery. And I don’t feel like I have a great answer for them a lot of times.”
He said that he recommends patients not smoke marijuana near the time of surgery. “My usual response is, ‘We don’t like smoke in or around surgery, so if you can switch over to oral forms, then I’m OK with it,’” he said. “What is the effect of that on wound healing or pain? I really don’t know.”
States are legalizing marijuana products for medical purposes and recreation at a fast rate—it’s legal at least for medical reasons in 33 states—and CBD shops are popping up everywhere, with CBD gummies, CBD chocolates, CBD caramels, and CBD cupcakes, as well as CBD lotions, balms, and salves. These, along with CBD and cannabis vaping pens and thumb drives, let people customize their CBD experiences.
All of this is tantalizing to customers and patients. But as patients become more interested in cannabis for their conditions, physicians, including otolaryngologists, are still awash in uncertainty and trepidation when it comes to whether and how to use marijuana products in their care plans. The interest level among otolaryngologists in medical marijuana products seems to be growing, and the push continues for more research, as well as the release of federal dollars and approval of policies to make this research more feasible.
Limited Data
Although he is in the state that could be considered the cannabis capital of the U.S., Dr. Winkler said he has never recommended any form of marijuana to patients, including CBD oil, as a medical therapy. His knowledge is unavoidably limited to the scant research and to the word of mouth of colleagues, he said. An anesthesiologist colleague who ran a pain clinic has told him that “he wasn’t super convinced that it had a huge effect in his practice.” It’s these types of observations and feedback on which Dr. Winkler largely relies.
“He said, in his opinion, the data on chronic pain was limited, and certainly in acute pain,” Dr. Winkler said. “But, of course, there are different formulations, and that was a while ago. So I’d be interested in using it—I’m not against using it—it’s just I would like to see more data.”
Dr. Winkler has done his own research, looking at incidence of facial trauma in Colorado in the two years before legalization of recreational marijuana compared with the two years after. He hypothesized that facial trauma incidence could go up if people behaved irresponsibly as a result of marijuana use, or perhaps go down if it had a calming effect and led to fewer assaults. Ultimately, there was no difference, although he acknowledged that two years is a relatively short time and behavioral patterns following legalization are undoubtedly continuing to be re-shaped.
Responding to the explosion of interest in cannabidiol—one of the more than 100 compounds, or cannabinoids, that are unique to the cannabis plant—and other marijuana products, the Food and Drug Administration (FDA) recently released a consumer update. It contained little medical guidance. “Other than one prescription drug product to treat rare, severe forms of epilepsy, the FDA has not approved any other CBD products, and there is very limited available information about CBD, including about its effects on the body,” the update said. It also said the FDA is looking into safety questions, including potential liver toxicity and cumulative exposure if CBD is used in a variety of forms at the same time, such as in the case of someone who eats CBD gummies, rubs CBD lotion on their skin, and vapes every night.
In what might be the most authoritative review undertaken on the limited research that has been conducted on medical marijuana products, including CBD oil and other forms, an expert committee of the National Academies of Science, Engineering, and Medicine determined that oral cannabinoids are “effective antiemetics” for adults with chemotherapy-induced nausea and vomiting. The group also determined that adults with chronic pain who were treated with cannabis or cannabinoids were more likely to experience clinically significant reduction in pain symptoms, and that using oral cannabinoids improves patient-reported spasticity symptoms in adults with multiple sclerosis.
“For these conditions, the effects of cannabinoids are modest,” the committee wrote. “For all other conditions evaluated, there is inadequate information to assess their effects.”
Among the report’s most prominent findings on the potentially negative effects of cannabis and cannabinoids, the committee found there is strong evidence of a statistical link between long-term cannabis smoking and worse respiratory symptoms and more frequent bronchitis episodes. But the group also found some evidence of no statistical link between cannabis smoking and the incidence of lung cancer.
[Cannabis] appears to be effective for many types of pain, but also has added beneficial effects, including anti-inflammatory effects, and help with sleep, appetite, and mood. —Greg Carter, MD
Of particular interest to the otolaryngology community, the committee also determined there is some, or “moderate,” evidence of no statistical link between cannabis use and head and neck cancer incidence. They defined “moderate” evidence as several findings from good- to fair-quality studies with very few or no credible opposing findings, with a general conclusion possible but with the limitation that chance, bias, and confounding factors can’t be ruled out with reasonable confidence.
The committee’s first two recommendations were to address research gaps and improve research quality. “This is a pivotal time in the world of cannabis policy and research,” committee members wrote. “Shifting public sentiment, conflicting and impeded scientific research, and legislative battles have fueled the debate about what, if any, harms or benefits can be attributed to the use of cannabis or its derivatives.”
Otolaryngology Research
The published literature on marijuana and cannabinoids in otolaryngology specifically is extremely thin. Earlier this year, researchers at Temple and Drexel Universities published a report on their search of the entire English literature available on PubMed, using a laundry list of otolaryngology search terms (Am J Otolaryngol [published online ahead of print May 30, 2019]. doi: 10.1016/j.amjoto.2019.05.025). They found just 79 unique publications. Most were published in the last decade and related to head and neck cancer. The researchers found a small number of studies suggesting cannabis may be useful for otolaryngology patients with blepharospasm, effects of radiation, and the psychological effects after getting a cancer diagnosis. “Further research is required to determine the potential therapeutic roles and adverse effects of cannabis on conditions related to otolaryngology,” researchers wrote.
Rafi Kabarriti, MD, assistant professor of radiation oncology at Montefiore Health System and Albert Einstein College of Medicine in New York, is one of the few researchers currently conducting research involving medical marijuana in otolaryngology. He is investigating its feasibility and potential benefits for patients with head and neck cancer undergoing chemoradiation. “Our motivation for this is that, first, our patients really struggle, as do all patients, undergoing radiation and chemotherapy for head and neck cancers,” he said. “We try to get these patients through these necessary treatments to get them through their cancer.”
The primary question is, “How easy is it to get medical marijuana in New York City for our patients?” he said. It seems like a rudimentary question, but even the accessibility is not well understood.
“I’ve treated a number of patients with head and neck cancer who have used cannabis, but not through a legal pathway, and what I’ve noticed in those patients is that they seem to tolerate treatment better than the ones who are not using cannabis through whatever means,” he added. The pilot study, with an enrollment goal of just 30 patients, will only include tinctures or the pill form of cannabis because of the concern that smoking or vaping could cause a burning sensation or exacerbate the side effects.
Greg Carter, MD, president of the American Academy of Cannabinoid Medicine and clinical professor at Washington State University Elson S. Floyd College of Medicine in Spokane, said that there are still misconceptions about medical marijuana. “I think a lot of healthcare providers still think cannabis is a dangerous drug with no medical benefits,” he said. “That simply is not true. Cannabis is not a cure-all and certainly does have side effects. However, if it is used under medical supervision, it can be remarkably helpful for many conditions.”
Some researchers say that CBD alone doesn’t produce much beyond a placebo effect, and that THC, a cannabinoid with psychoactive effects, is needed to produce a traditionally therapeutic effect. Dr. Carter said that’s an area that also needs more inquiry. “I think we need to do more research on CBD and some other cannabinoids, including CBN [cannabinol],” said Dr. Carter. “However, there is some evidence that THC works better and is less intoxicating when it is in the presence of other cannabinoids.”
Cannabis use in the treatment of pain, epilepsy, and cancer is among the most prominent areas of research now. Overall, he said, the research base for cannabis is “pretty massive.”
“However, a lot of that work is studies done in animals,” he said. “There are a lot of human studies, but mostly with THC. Still a lot of work needs to be done with CBD and the many other cannabinoids.”
In his view, he said, the most important thing for physicians to know about medical marijuana in order to best treat their patients is that “cannabis does appear to be safe from a pharmacological perspective.”
“It appears to be effective for many types of pain, but also has added beneficial effects, including anti-inflammatory effects, help with sleep, appetite, mood, among many other beneficial effects,” Dr. Carter said.
I’ve treated a number of patients with head and neck cancer who have used cannabis, … and they seem to tolerate treatment better than the ones who are not using cannabis. —Rafi Kabarriti, MD
AMA and ACP Positions
Leading medical associations have published position papers on medical marijuana, but both the American Medical Association and American College of Physicians declined to grant interviews to ENTtoday for further guidance on how physicians can navigate the confusing landscape, saying they had nothing to add beyond the publications already available.
In addition to calling for steps designed to promote additional research into medical marijuana, the American College of Physicians position paper encourages the use of non-smoked forms of THC that have “proven therapeutic value.” The college also urges authorities to do an evidence-based review of marijuana’s status as a Schedule I controlled substance, to see whether it should be reclassified, and “strongly supports” exemption from federal criminal prosecution, civil liability, or professional sanctioning for physicians prescribing or dispensing medical marijuana in accordance with state law.
The AMA also calls for steps for more high-quality research and says it “believes that cannabis for medicinal use should not be legalized through the state legislative, ballot initiative, or referendum process.” The association also says it supports legislation granting immunity to physicians who recommend cannabis for medical conditions in accordance with state laws. Patient care, the policy says, “requires the free and unfettered exchange of information on treatment alternatives and that discussion of these alternatives between physicians and patients should not subject either party to criminal sanctions.”
Although the interest in medical marijuana seems to be keener in neurology, mainly for a role in epilepsy and multiple sclerosis, and rheumatology, which involves many disorders that bring chronic pain, otolaryngologists are also eager to learn more about medical marijuana, Dr. Winkler said. Recently, at a medical meeting in Portland, Ore., a colleague suggested they do a study looking at post-operative pain with or without CBD.
“Right now it seems like CBD oil is the cure-all for everything, which of course it’s not,” he said. “But, that said, what things might it be beneficial for? And we all talk about that, and maybe we’ll do some studies in the near future. … It’s one of those things that we all think could have some potential—just the studies, to my knowledge, haven’t been done. While CBD oil and cannabis may have potential as a therapy for a variety of diseases, we need more well-controlled studies to guide our clinical practices.”
Thomas R. Collins is a freelance medical writer based in Florida.
Simple Study Not So Simple When It’s Marijuana
After noticing that patients who said they used marijuana seemed to do better with radiation and chemotherapy than those who did not, Rafi Kabarriti, MD, a rare researcher doing work involving marijuana and otolaryngology, thought it was time to collect some hard data on the topic. He wanted to see how easy it was for patients to obtain and stay on a dosing plan for medical marijuana and how it affected the tolerability of their chemoradiation.
It proved to be a much more challenging process than any other trial on which he has worked. “This one took three to four times the effort,” said Dr. Kabarriti.
He preferred to randomize patients to either receive New York State-approved medical marijuana or not, but that was not feasible. The only way to randomize would be to obtain medical marijuana from the National Institute on Drug Abuse, a process that can take years, he said. So, he settled for a pilot study of just 30 patients, with no randomization.
Also, because marijuana is classified as a Schedule I drug—meaning that, in the eyes of the federal government, it has “no currently accepted medical use and a high potential for abuse,” the same category as heroin, LSD, and ecstasy—he wouldn’t be able to dispense any medical marijuana on site, and no university personnel could do any of the dispensing regardless. Instead, university researchers had to collaborate with pharmacists at dispensaries outside their institution, confirming with them that patients were in fact obtaining and taking their medical marijuana in tincture or pill form. They settled on those forms to avoid the possible side effects of smoking or vaping.
“We had multiple hurdles to be able to get our trial up and started,” he said. “It was a big challenge, but we were persistent, and that’s why we’re probably one of the few ones in the country to have it [a medical marijuana study] open.”
It’s no wonder so few clinical studies are being performed on medical marijuana, even as public interest in medical marijuana and CBD skyrockets.
After a large-scale review of the available literature on cannabis and its cannabinoids, the National Academies of Science, Engineering, and Medicine urged public, philanthropic, private, and clinical research groups to support cannabis research, and urged federal authorities to develop research standards and benchmarks to produce high-quality research.
For now, Dr. Kabarriti said, “It’s almost impossible to make definitive recommendations,” he said. “We should treat it as we treat every other drug, every other medication, every other therapy we offer our patients, where we don’t just randomly [try something] because we think it works,” he said. “We should do it and investigate whether it works or not before we make firm recommendations, and this is exactly what we are doing.”—TRC