November/December 2020 Issue
Cannabis in Cancer Care
By Jamie Santa Cruz
Vol. 22, No. 9, P. 40
An Evaluation of the Research and Recommendations for Counseling Patients
Cannabis use is widespread among cancer patients in the United States. A 2017 survey in Washington State, where cannabis is legal for both medicinal and recreational use, found that up to one-quarter of cancer patients were using cannabis in some form—and almost three-quarters of patients wanted information on cannabis from their oncologists.1
So does cannabis have value for symptom management in a cancer context? Research on this subject currently is underdeveloped, but the studies that exist suggest the answer likely is yes—cannabis may have a meaningful clinical impact on several common cancer-related symptoms, including pain, loss of appetite, and chemotherapy-induced nausea and vomiting.
What Is Cannabis?
The cannabis plant contains more than 500 natural compounds, many of which have bioactive effects.2 These compounds include terpenoids, which give cannabis its distinctive aroma, and flavonoids, which are found in many vegetables and spices and are thought to be responsible for many of their health benefits.3 The plant also contains cannabinoids, which are chemicals that operate on the body’s cannabinoid receptors. So far, more than 100 cannabinoids have been identified in the cannabis plant, but the two believed to have the greatest bioactive effects are tetrahydrocannabinol (THC) and cannabidiol (CBD).2
The two main cannabinoid receptors in the human body are CB1 and CB2. These receptors are present in all brain regions and throughout the peripheral nervous system, but they’re particularly prevalent in the hippocampus, amygdala, thalamus, and the cortex—brain regions associated with mood, depression, anxiety, memory, and pain.3
Cannabis can be taken in several forms. It can be inhaled, consumed by mouth (in baked goods, teas, oils, capsules, etc), or taken in the form of topicals or suppositories (See “CBD Dosing and Methods of Administration” on page 12). In addition, there are several pharmaceutical products made from cannabis. These include dronabinol and nabilone, which are synthetic forms of THC approved by the FDA. Another available product is nabiximols, which is an oromucosal spray made from a cannabis extract and that contains specific ratios of various cannabinoids; however, this product currently isn’t approved for use in the United States.
The Regulatory Environment
At present, research on the therapeutic value of cannabis (for cancer and other conditions) is limited. Though cannabis currently is legal at least for medicinal use in 33 states, the federal government designates it a Schedule I substance. This means there are tight restrictions on the study of whole-plant cannabis. For this reason, much of the evidence for a therapeutic effect of whole-plant cannabis comes from anecdotal reports and survey data. Since the THC-based drugs dronabinol and nabilone are FDA approved pharmaceuticals, it’s easier to conduct studies on them. However, these drugs contain only a single cannabinoid in isolation, which is likely to have different effects than whole-plant cannabis.
Over one-half of cancer patients experience at least moderate pain.3 Opioids are the first-line treatment, but they have significant drawbacks—including that they often don’t provide sufficient pain relief and are highly addictive.
Several recent reviews and meta-analyses appear to confirm that cannabis has a clinically meaningful impact on chronic pain.4 One of these reviews, published in 2015, suggested that the effect was “modest,”5 but a 2017 report from the National Academies of Sciences, Engineering, and Medicine (NASEM) concluded that pain is the therapeutic realm for which there’s the strongest evidence for a beneficial effect of cannabis.6 An important caveat, however, is that the reviews just mentioned were looking at the effects of cannabis on chronic pain generally, not cancer pain specifically.
As for clinical trials on cancer pain in particular, they are limited. A 2017 review article of five clinical studies found that cannabis appears to reduce chronic or neuropathic pain in patients with advanced cancer. However, the review also noted that most studies are small and lack statistical power.7
Beyond the research contained in that 2017 review, only a handful of studies exist. One pair of randomized controlled trials examined the impact of nabiximols (containing a 1:1 ratio of THC to CBD) in cancer patients who weren’t getting effective pain relief from opiates. The researchers found that the patients receiving cannabinoids didn’t experience greater pain relief that those in the control group—but a subgroup analysis found patients from the United States did experience a reduction in pain.8
In a 2018 prospective analysis of patients with cancer, researchers measured patients’ pain levels at the start of the study and again after six months of treatment with cannabis. They found that 63% of participants reported pain levels of eight to 10 (on a 10-point scale) at the start of the study, but only 4.6% reported pain at that same intensity at the conclusion of the intervention. This finding suggests a considerable benefit from cannabis, but the key weakness of the study was that there was no control group.9
A particular type of pain associated with cancer is chemotherapy-induced peripheral neuropathy. The exact mechanisms involved in peripheral neuropathy—and the exact mechanisms by which cannabis might help—are unknown. However, it appears likely that CB1 receptors are involved.3
Several placebo-controlled trials in humans have found that smoked or vaporized cannabis reduces neuropathic pain stemming from various causes.10-15 So far, only one small placebo-controlled trial has examined the impact of a cannabis product on neuropathic pain caused by chemotherapy in particular16; however, there are several animal studies of neuropathy stemming from chemotherapy, and these animal models suggest that CBD appears to help prevent neuropathy.3
Some studies suggest that opioid users who also use cannabis need lower doses of opiates to manage their pain.17,18 According to Amber Kleckner, PhD, a research assistant professor in the department of surgery and the Cancer Control Program at the University of Rochester in Rochester, New York, the implication is that cannabis “can potentiate opiate effect.” But not all studies have observed such an effect, she adds, leading to uncertainty about exactly how much of an impact cannabis has on opiate use.19
An important complicating factor in the study of cannabis for pain is that different kinds of pain may respond to cannabis differently. Even in a cancer-specific context, what may be effective for one type of pain (such as radiation-induced pelvic pain) might not be effective for another (such as chemotherapy-induced neuropathic pain).3 Thus, while anecdotal reports widely suggest that cannabis is effective at managing cancer pain,7 more research is needed to tease out specifics.
Nausea and Vomiting
As mentioned earlier, currently there are two synthetic versions of THC that have been FDA approved. Both were developed in the 1970s as antiemetics, and both were shown to be equal or superior in efficacy to other pharmaceutical antiemetics available at the time.20
In the past several decades, newer pharmaceutical antiemetics have been developed, but few head-to-head comparisons have been made of these modern antiemetics against THC-based drugs. However, one study did evaluate dronabinol against ondansetron (a newer antiemetic) for treatment of delayed nausea and vomiting associated with chemotherapy, and the two were found to be approximately equal in efficacy.21
Nevertheless, these studies focused on THC-based pharmaceuticals, but what about whole-plant cannabis?
Unfortunately, there are few randomized controlled trials on whole-plant cannabis for nausea. Yet, patients widely report a benefit of whole-plant cannabis in reducing nausea,3 and there’s some evidence from observational studies suggesting cannabis is efficacious. For example, researchers in Israel used a toxicity scale to grade the symptoms of a sample of 106 oncology patients who previously hadn’t been using cannabis, and they found that the percentage of participants with mild to moderate nausea at baseline was 65%. At follow-up after six to eight weeks of continuous cannabis use, the percentage reporting that same level of nausea was just 27%.22
According to Kelay Trentham, MS, RDN, CSO, an oncology dietitian at the MultiCare Regional Cancer Center in Tacoma, Washington, one factor that may explain the strongly positive results in the Israeli study was that participants could adjust the amount of cannabis they were using. “They were able to titrate the dose to the degree that worked for them as far as symptom management,” Trentham says. This may have allowed patients to find the dose that produced the greatest benefit (unlike in a randomized controlled trial, where patients would have to take a prescribed dose). That said, it’s notable that the study started with a higher number of participants, but 25 dropped out of the study within a week, primarily because of cannabis’ side effects.
In addition to the above research, two other studies deserve mention. In 2001, researchers from the University of Vermont reviewed a series of unpublished technical reports from six different states and found that 70% to 100% of subjects who were smoking cannabis saw a reduction in nausea.23 Second, a small placebo-controlled trial evaluated the efficacy of nabiximols (the spray mentioned earlier that’s from a cannabis extract). This trial included just 16 patients, but the researchers found that nabiximols was superior to placebo in reducing nausea.24
In sum, there are gaps in the research, but existing research already provides “very strong evidence that cannabis is useful for chemotherapy-induced vomiting and nausea,” according to Donald Abrams, MD, a professor of medicine at the University of California San Francisco and an integrative oncologist at the Osher Center for Integrative Medicine. Not only is cannabis effective but it also has key advantages over pharmaceutical antiemetics, he says. In fact, according to Abrams, it’s the only antiemetic that also stimulates appetite.
In addition, Kleckner says, cannabis combats both vomiting and nausea. “We have pretty good drugs to control the vomiting. We don’t have very good drugs to control the nausea,” she says.
Anecdotally, cannabis has a reputation for stimulating appetite, and research has confirmed that this effect indeed does exist—at least in some settings.25-28 But what are the effects in cancer patients?
On the one hand, observational evidence suggests cannabis reduces weight loss in a cancer context.22 As for clinical trials, a few have found that cannabis-derived treatments produce improvement in appetite,9,29,30 and at least one of these—a randomized controlled trial of 65 advanced cancer patients in Mexico—found that the improvement in appetite translated into greater caloric intake as well as significantly improved quality of life.30
On the other hand, several clinical studies show an improvement in appetite but not an increase in caloric intake9,29 or fail to find an improvement in appetite at all. In one randomized trial of 243 patients with advanced cancer, participants received cannabis extract, THC, or placebo. Neither the extract nor isolated THC was more effective than placebo for stimulating appetite.31
In another study, 469 patients with advanced cancer who had experienced weight loss were assigned to receive either dronabinol or megestrol acetate (a non–cannabis-based appetite stimulant), or a combination of dronabinol plus megestrol. Those taking megestrol alone reported greater weight gain and improvement in appetite than those taking dronabinol alone or those taking megestrol in combination with dronabinol.32 The 2017 NASEM report concluded that there was insufficient evidence to support the use of cannabis to treat cancer-related weight loss and loss of appetite.6
According to Abrams, a possible reason why randomized controlled trials haven’t consistently shown a benefit of cannabis for appetite stimulation and weight gain among cancer patients is that most of these trials have focused on dronabinol or nabilone—which contain only isolated THC without the hundreds of other bioactive compounds present in whole-plant cannabis. “People believe that the so-called entourage effect—the mix of the cannabinoids, the terpenoids, and the flavonoids—produces a sum that is greater than the parts,” Abrams says. “Anyone who has ever used cannabis knows that you get the munchies.”
While there are apparent advantages to using cannabis or cannabis-based products within a cancer context, dietitians and patients alike should be aware of the potential side effects. “If they’re using any THC-based preparation, the possibility of the psychoactive side effects is very real,” Trentham says. “It really doesn’t matter if it’s a synthetic THC or if it’s a cannabis-based THC.”
Side effects of THC may include confusion, disorientation, hallucination, dizziness, changes in psychomotor speed, loss of balance, changes in blood pressure, and tachycardia (fast heart rate). Furthermore, although cannabis is used to treat nausea, excessive use of THC-based products can cause severe nausea (cannabinoid hyperemesis syndrome), though this is rare in medical users. Importantly, CBD doesn’t have these same effects, and the presence of CBD appears to increase the tolerability of THC. However, the presence of CBD also may reduce some of THC’s benefts.33 According to Abrams, “CBD decreases the psychoactivity of THC, [but] it also decreases its therapeutic efficacy.”
Takeaways for Dietitians
The research on cannabis for cancer care remains scant. Most randomized controlled trials have focused on isolated cannabinoids, which may have different effects than whole-plant products. While randomized controlled trials of whole-plant cannabis are few, observational evidence and patient reports continue to suggest that cannabis holds promise for cancer care.3,7,9 In light of this information, RDs can keep these suggestions in mind when counseling clients and patients.
1. Prepare for conversations. Dietitians should become familiar with the research on cannabis, including its strengths and weaknesses to have a conversation with cancer patients who are interested, Trentham says. Part of this research should include familiarizing yourself with the regulatory environment specific to your state beyond whether cannabis is legal. “Is it tested for pesticides, is it tested for microbials, is it tested for fungal contamination?” Trentham asks. “Understand your local legal context—especially if cannabis is available to people without a doctor’s authorization.”
2. Learn the nuances between whole-plant cannabis and pharmaceutical preparations. The question of whether to use whole-plant cannabis vs preparations of specific cannabinoids depends on context. Kleckner’s hunch is that “the full plant would probably be more beneficial”—namely because cannabis in its whole-plant form contains not just THC and CBD but also hundreds of other bioactive compounds that likely provide therapeutic benefits.
That said, medical cannabis still isn’t legal in all states, so pharmaceutical preparations of single cannabinoids (ie, dronabinol, nabilone) may be the only viable option. Even where cannabis is legal, often there’s no standardization in cannabis products. “Each plant is going to be different,” Kleckner says. “If you go to a dispensary, you could keep buying the exact same product, but each product is going to be slightly different just due to differences in the agriculture of the plant.” By contrast, “If you take concentrated THC, you know exactly what you’re going to get every time, which is definitely a good thing when you’re trying to treat a symptom.”
Ultimately, Kleckner says, the decision about which product to use must be based on the preferences of patients and their health care providers and the expectations and risk tolerance each product carries.
As for which administration route for whole-plant cannabis is best, Kleckner says it’s up to the patient. Inhalation has the benefit of acting quickly—patients will experience an effect within minutes, but it also means more variability in terms of the quantity the patient takes in, and it’s associated with smoking, which carries a stigma. Kleckner tends to recommend oromucosal sprays, but ultimately, she says, “it’s just a matter of personal preference.”
3. Don’t think of cannabis as a first-line treatment. According to Kleckner, it’s justifiable to try cannabis if other treatments aren’t working. But due to the regulatory environment, researchers haven’t been able to study cannabis sufficiently to recommend it for first-line use. “People like to think of it as being natural and [therefore] benign,” she says. But “there just hasn’t been enough research yet. The [long-term] safety hasn’t been established and the long-term effects haven’t been established.” The bottom line: Be open—but also be cautious.
— Jamie Santa Cruz is a freelance writer of health and medical topics based in Parker, Colorado.
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