Author: Chase Doyle
Although medical marijuana is now legal in more than 30 states, many clinicians are unfamiliar with how to manage patients using medical marijuana and may even be uncomfortable doing so.
At the 2019 Hematology/Oncology Pharmacy Association annual meeting, Lisa M. Holle, PharmD, an associate clinical professor at the University of Connecticut School of Pharmacy, in Storrs, shared supportive data for various indications for medical marijuana and cannabidiol oil relevant to the oncology setting and discussed common and serious adverse effects (AEs) associated with these products, among other management considerations.
Differences by State
As Dr. Holle reported, the laws vary greatly among the 33 states that have approved the use of medical marijuana, including aspects related to patient certification, possession amounts and whether cultivation is allowed. In addition, pharmacists have oversight over dispensaries in only six states; in most medical marijuana dispensaries, patients are receiving suggestions from people without a health care background, Dr. Holle said. “If you are in a state with a medicinal marijuana program, I would encourage you to review the regulations and laws because they do vary by state,” she said. “One constant, however, is that prescribers with a DEA [Drug Enforcement Administration] license are unable to prescribe medicinal marijuana because it’s against federal law.”
Cancer-Related Pain, Anorexia
With respect to cancer-associated pain and chronic noncancer pain, benefits have been shown, Dr. Holle said, but they have been modest and are primarily associated with neuropathic pain. Some of the evidence comes from randomized, but “very small,” controlled trials, so “it’s hard to know whether the products our patients are using may have the same sort of effect,” she noted.
Mood and Sleep Aid?
Many patients with insomnia, possibly caused by cancer-related therapies, also have reported positive effects from cannabidiol extracts or medical marijuana with a high percentage of cannabidiol. One meta-analysis of 19 placebo-controlled trials involving a variety of marijuana products demonstrated greater improvement in sleep quality (JAMA 2015;313:2456-2473). These data could support the use of cannabidiol or cannabinoids for insomnia, Dr. Holle said.
Although some patients searching for a better treatment for depression or anxiety have reported improved outcomes after taking cannabidiol products, according to Dr. Holle, the data are limited with respect to patients with cancer. “There have been no well-designed trials looking at depression, but one study [JAMA 2015;313(24):2456-2473] showed a positive influence on social anxiety among patients using cannabis for chronic pain.”
Many studies have explored cannabis for the treatment of cancer, but the data have been largely disappointing. One retrospective study of patients receiving nivolumab (Opdivo, Bristol-Myers Squibb) in Israel, however, showed a “surprising reduction” in relative risk among users of cannabis with advanced melanoma, non-small cell lung cancer or renal cell carcinoma (Ann Oncol 2017;28:abstract 1545PD), Dr. Holle noted. Of the 140 patients included in the analysis, 89 were given nivolumab alone, whereas the other 51 were given cannabis with nivolumab.
“In a multivariant model, cannabis was the only factor which reduced the relative risk, and it did not affect overall or progression-free survival,” Dr. Holle said. “We need to verify this in a large prospective trial, but these are the only data I know looking at the effect of cannabis in a large group of patients receiving treatment for many different tumor types.”
But as with any therapy, efficacy is just one piece of the puzzle; AEs also have to be assessed, and in the case of cannabis, that’s a potential downside. Of note, patients receiving products combining THC and cannabidiol generally will have more AEs than those taking cannabidiol alone, Dr. Holle noted.
With respect to drug interactions, Dr. Holle noted that other central nervous system depressants could worsen AEs. Moreover, because both cannabidiol and THC are modulated by the cytochrome P450 (CYP) system and metabolized by the liver, she said there is the potential for CYP-mediated drug interactions.
Noting that few drug interactions with THC products have been reported in the literature, she cautioned that “doesn’t mean that it can’t happen. It’s very important when monitoring patients who are receiving medical marijuana to understand that this is another drug they’re using.”
With an absence of well-designed trials, which are “almost impossible to conduct given the number of different products available,” Dr. Holle said, documenting patient-reported outcomes and AEs in the electronic health record is a “good step in the right direction to better understanding how these products work in our patients.”
Finally, it’s also important to educate patients. “We know that if a patient consumes a cannabis product that they will experience some psychoactive effects, and they probably shouldn’t be driving,” she said. “It’s recommended that a patient wait at least three hours after consumption before driving, but the level of psychoactive substance in the body depends on whether one is a chronic or intermittent user.”
Christy Harris, PharmD, from Dana-Farber Cancer Institute, in Boston, underscored the huge interest of patients in cannabis and its derivatives since the passing of the 2018 Farm Bill by Congress. “The new elixir of life is apparently CBD [cannabidiol] oil,” said Dr. Harris, who noted, however, that the concentrations of medical marijuana products are largely questionable and depend on whether they are topical, ingested or inhaled. “Few patients are actually at a steady state with marijuana, and the dosing depends on whether they are using the plant or just the THC, or just the CBD.”
Patients also can obtain varying concentrations at different sites, and the products themselves may not be labeled accurately. A study of online cannabidiol products found that 70% had higher or lower concentrations than what was on the label (JAMA 2017;318:1708-1709).
“This doesn’t surprise me because we already know this about our supplements—they’re not regulated,” Dr. Harris said. “But this can be of concern when we were trying to draw conclusions from the studies themselves.”