Navigating the Landscape of Cannabis Use in Oncology

Although cannabis is a Schedule I drug, which categorizes it as having no accepted medical use, more and more states are legalizing it for recreational and/or medicinal use across the country, explained Marie Parish, PharmD, BCOP, BCPS, a clinical oncology pharmacist at Mayo Clinic, during a presentation at the Hematology/Oncology Pharmacy Association Annual Conference 2024 in Tampa, Florida.

Image credit: Irina | stock.adobe.com

“I am fortunate enough to work in a state where cannabis is legal for both recreational and medicinal use. I have seen a tremendous uptick in the number of patients that have asked me about cannabis products to help with their symptom management from both their cancer and their treatment,” Parish said during the session. “Regardless of whether or not you work in a state that currently allows cannabis to be legal, I think that the legal landscape is changing very rapidly. If you don't now, I think you are going to experience questions in the near future.”

Parish explained further that the human body has an endogenous cannabinoid system that has the primary goal of maintaining homeostasis. The primary components of the human endocannabinoid system are the endogenous cannabinoids, the receptors on which endogenous cannabinoids act, and the enzymes involved in the degradation of endogenous cannabinoids.

“Given that our endocannabinoid system’s whole role is to maintain homeostasis, when we introduce exogenous cannabinoids, we have the opportunity to either amplify or dampen the effects that the endogenous cannabinoids would normally try to maintain at baseline,” Parish said during the session. “[Additionally,] when a patient is choosing a cannabis product to use, there's a number of different things that they have to consider because the different types are going to elicit different responses, and different side effects can be managed appropriately.”

One of the things patients should take into consideration is the strain of cannabis, which includes cannabis sativa, cannabis indica, and cannabis ruderalis. Cannabis sativa is considered to be the activating strain, as it has a higher ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD). Parish explained further that this ratio is in contrast to cannabis indica, which is a more sedating strain, because it has a higher ratio of CBD to THC. Cannabis ruderalis, on the other hand, is a third strain, but it has low THC content, so it is not as frequently discussed as the other 2 for clinical and recreational use. Finally, hybrids are also becoming more and more popular, and there are strains that are specifically grown with varying ratios of THC and CBD.

“Realistically in practice, [these strains are] what your patients are going to be choosing between,” Parish said during the session. “Sativa is the activating strain and that is going to cause more of a mental high, so if your patient is looking for increased alertness, increased energy, or if they really crave that euphoric feeling or increased creativity, sativa might be a better option for them. The more sedating strain is going to produce more of a body high, so if your patient is looking for relaxation, help with sleep, and help with pain relief, indica is usually a more appropriate option.”

Parish explained further that indica is also indicated for increased appetite, so for patients who are experiencing difficulty with eating while they're on an oncology treatment, indica is usually a better option. CBD can also be used alone or in combination with THC-based products. However, although CBD does not have the same neurologic intoxication effects that THC does, it has agonist activity at dopamine and serotonin receptors, which has implications for use in depression and anxiety.

“The thing to know about CBD, and why it may not always be the most appropriate option for our specific patient population, is it has very, very low bioavailability, it is very poorly absorbed, and it undergoes a high rate of first pass metabolism,” Parish said during the session. “The way to overcome that is to take it with a very, very high fat meal, which for the general population may or may not be an issue, but for our oncology patients, it is oftentimes hard to get them to eat a meal at all, let alone a meal that is very, very high in fat. So [I’m] not saying CBD alone is off the table for oncology patients, but they might not derive as much benefit from it given the pharmacokinetic limitations of CBD.”

After a patient chooses a strain, they then have to choose a drug delivery system, such as smoking or vaporizing, liquid extracts, and botanicals, the latter of which can come in capsules, sublingual tablets, sprays, and suppositories. Ultimately, Parish explained that there are a number of different methods of cannabis delivery for patients that can optimize the best form for them to intake the drug.

Additionally, Parish noted there are also 2 FDA-approved medications that are synthetic cannabinoids, which include nabilone (Cesamet; Bausch Health) and dronabinol (Marinol; Solvay Pharmaceuticals). Both are FDA approved to prevent and treat chemotherapy-induced nausea and vomiting (CINV).

“This brings us to our oncology uses. I want to preface this by saying the data surrounding specific uses in this space is limited and often conflicting,” Parish said during the session. “That has a lot to do with the fact that this is a Schedule I substance, and it is very challenging to develop well-designed, well-powered, randomized control trials using this substance. As the legal landscape changes, I anticipate that that is going to change, and we will continue to get better data. But as of right now, you are not going to see as much robust data as you would with our traditional pharmaceutical agents.”

However, there are a number of oncology uses for cannabis that have shown some benefit, according to Parish. The primary indications that have demonstrated benefit are CINV, anxiety, and pain. Specifically, Parish noted that CINV has the most robust data supporting the use of cannabis to treat it, and THC is the driver from a mechanism standpoint.

“What's interesting to note is that there is more central activity at lower doses of THC, and there is more activity peripherally at higher doses,” Parish said during the session. “If we think that most of the anti-nausea effect is coming centrally, this is a perfect example of more isn't always better.”

There also have not been any trials to investigate CBD alone in treating CINV, so it is still uncertain what value CBD brings to CINV treatment. For this reason, THC is believed to be doing the heavy lifting in the treatment of CINV, according to Parish.

Anxiety and depression are another area in which both THC and CBD are used because they both have slightly different mechanisms of action, Parish explained. THC will inhibit GABA, which stimulates glutamate, releasing dopamine that leads to a euphoric or pleasure response. CBD, however, is an agonist with both the dopamine and serotonin receptors.
“What's cool about CBD is that it can contribute to the anti-depressive and anxiety effects without that euphoria,” Parish said during the session. “If you have a patient who is very interested in exploring this option for their mental health needs, but they don't want to feel stoned all the time, giving them a formulated product of CBD and THC will dampen some of the psychoactive effects without minimizing the clinical benefit. So [it’s] something to keep in mind if that's something your patient really wants to explore.”

The last indication for cannabis is pain, which Parish noted is the indication about which she gets asked the most questions.

“I get asked far and away the most frequently about pain, which is really disappointing because it's the area that needs the most help from a data standpoint,” Parish said during the session. “This is something I talk about with my patients all the time. If they want to try a cannabis-based product for their pain, I will support them in that, but I try to level set with them. Cannabis will likely never completely replace the existing pain regimen that they have. It might increase the time between a need for a dose increase or a frequency increase, but rarely, if ever, are you going to be able to completely get off your opioids with the help of cannabis-based products alone.”

REFERENCE

Parish M. Cannabinoids and the Oncology Patient: Pearls for Pharmacists. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2024; Tampa, Florida; April 3-6, 2024.