Cannabinoids in Oncology: A Growing Role

At the 2019 ASCO annual meeting in Chicago, Mellar Davis, MD, of Geisinger Medical Center in Danville, Pennsylvania, discussed the interactions of cannabis with cancer therapies, the use of cannabis in older cancer patients, the pros and cons of cannabis use, and the legal and ethical aspects of using cannabis in the U.S. Following is a transcript of his remarks: There’s a lot of animal data that suggests that cannabis can promote cancer in patients in very anaplastic cancers, CB1 and CB2 receptors, or be elevated or increased in expression. That may be a cancer-promoting effect. That may be, actually, a way of suppressing cancers that occur. Cannabis also works in an anti-neoplastic fashion, so not only directly through the receptor, but also through other receptors or through blocking anti-angiogenesis. There are multiple effects that cannabis can have on various cancers. There is some fledgling data on the use of cannabis in patients with gliomas that is promising, but again, only a small amount of data is available. Then, there are some anecdotal responses that have been noted. It’s also been noted in a retrospective review that cannabis actually blocks the responses that occur with checkpoint inhibitors. On the other hand, CBD or cannabidiol actually reduces graft-versus-host disease. There are mixed effects that can occur in patients with advanced cancers. As far as symptoms are concerned, there are potential multiple benefits that can occur by using cannabis, usually in lower doses. The trouble that’s occurring now is that what is offered in dispensaries or on the streets is much higher than doses that have been used to reduce, for instance, nausea and vomiting or pain, which are the two main reasons patients with cancer take cannabis. The difficulty that occurs is that what’s available now may be actually too high. The higher the doses, the more side effects you get into, the psychomimetic effects that occur with it, the fall risks, and things like that. As far as elderly patients are concerned, they’re on multiple drugs, and THC and cannabidiol, the two major cannabis derivatives, do have drug interactions. They’ll block or stimulate the mixed-function oxidase, so you can get into drug interactions. Because there’s a narrower therapeutic margin, the risks of falls are there, particularly combined with, perhaps, opioids, but particularly with alcohol. Oftentimes, we think that the elderly aren’t using cannabis, but in fact, probably about 20% of cancer patients are using cannabis, and at least half of those are over the age of 65. We need to ask them if they are, and instruct them on the use of cannabis, and the risks and benefits that occur so that they can safely use it if they choose to do so. The difficulty in the United States is that we don’t have any control over what they get in the dispensaries, so you’re not writing for a certain amount of cannabidiol or THC that occurs. You’re really at the mercy of whoever is at the dispensaries. You can make recommendations, but they may not be followed. Patients often don’t know how much they’re on or what they’re taking. We, as palliative specialists, at least at the Geisinger, are not really certifying people for cannabis for that reason, because we worry about the drug interactions with some of the drugs we use for symptom benefit. Now the medical-legal aspect of cannabis has been, really, yin-yang in the United States. It was commonly used before 1937, but with the Marijuana Tax Act and then changes in regulations, it actually dropped to zero, though there were no studies to suggest that should occur. There weren’t negative studies that were going on at the time. It was more of a political act. The AMA, at the time, really recommended that studies be done with marijuana to look at the risks and benefits, but it really wasn’t taken up by the federal government, so it became, in 1970, a Schedule 1 drug, which means that it’s a high-risk drug with no clinical benefits to it, but yet, there was no data at all to suggest that, no randomized trials to do that. Then, there was a move in the ’90s to legalize it in the States so that it became not a prescribed drug, but you recommended that a patient was a candidate for the use of cannabis, so it became more of a political drug in the U.S. All of that has really hampered the development of research trials looking at cannabis. What is its true value in treating people both from a patient-centered perspective as well as from a cancer-centered perspective? There are large gaps that we have.