While many states have rushed to legalize cannabis, evidence for its medicinal use remains ‘paltry.’ However, physicians must be willing to talk with patients who want to use it.
By Nicole Wetsman
With medical and recreational cannabis legal across most of the United States and Canada, patients are turning to the drug as an alternative treatment for a wide range of ailments, including arthritis and other types of joint pain. Using cannabis as a pain management strategy for severe arthritis may, for example, be an appealing alternative to opioids or other pharmaceuticals for some patients.
However, despite the legalization of the compound for medical and other uses, scientists and doctors still know very little about how effective cannabis actually is. Though many patients report positive benefits, and there is some evidence in support, there is very little research on how—or if—the drug works, which makes counseling patients who are interested in using the drug challenging.
“The concern for us as physicians is that the evidence is paltry,” said Mary Ann Fitzcharles, MB, ChB, MRCP(UK), FRCP(C), associate professor of medicine in the Division of Rheumatology at McGill University. “We have to keep a very open mind. Cannabinoids might be wonderful products for patients with musculoskeletal conditions, but honestly, we don’t know.”
Evidence for the use of cannabis
In March, doctors in Scotland sequenced the genome of a woman who—to their surprise—seemed to feel no pain, even though she underwent a normally painful surgical procedure and was found to have severe arthritis in her hip along with joint degeneration.1 The analysis found that she had a mutation that affected her body’s ability to break down anandamide, a neurotransmitter that binds to cannabinoid receptors—which might explain her resistance to pain.
Although it’s only one case study, and pain is a complicated phenotype governed by a wide range of genes, the patient is an interesting case study in the role of the cannabinoid system in joint pain, said Richard Miller, PhD, a professor in the department of pharmacology at Northwestern University. “It’s extremely striking, and you would imagine it indicates that if you manipulate the cannabinoid system in some way, you reduce pain with arthritis,” he said.
There are other, biological reasons that some scientists believe cannabis and cannabinoids can ease arthritic joint pain, Miller said. The endocannabinoid pain regulating system, which responds to cannabinoids, has receptors in nerve and joint tissue. Activating cannabinoid receptors has been shown to have pain-reducing effects in rodent models of pain, for example, and has also been shown2 to reduce joint inflammation that causes pain in rheumatoid arthritis. In a 2014 study of mouse models of inflammation, administering an enzyme that would modulate the endocannabinoid system showed anti-inflammatory effects.3
“There are mechanisms you would think would come into play, and a reasonable scientific rationale for these things,” Miller said.
In addition, some clinical trials have shown some efficacy from cannabis in pain and in arthritic pain. A 2006 study of Sativex,4 a cannabis-based medicine, for example, randomized 58 patients with rheumatoid arthritis to receive either the medication or a placebo over a 5-week period. The group receiving the drug had small but significant improvements in pain on movement, pain at rest, and quality of sleep, the study found.
Fitzcharles conducted a systematic review of randomized controlled trials on cannabis and rheumatic diseases in 2016.5 Four studies meeting the criteria were identified, which included patients with rheumatoid arthritis, fibromyalgia, and osteoarthritis. The sample size was small—only 203 patients were included—but the analysis showed that cannabinoids improved pain. However, nearly half of the patients reported side effects such as dizziness and cognitive problems. The study, which was published in the journal Arthritis Care and Research, noted that it did not offer sufficient evidence to actively recommend the treatment to patients.
Finding completed, well-controlled studies on cannabis is challenging at the moment, in part because the type and amount of cannabinoids contained in the drug varies widely. “A great challenge is the diversity of the molecular content of this herbal product,” Fitzcharles said. A grower might claim a strain has 10% tetrahydrocannabinol (THC, the main active ingredient in cannabis), for example, but it’s hard to know for sure. In addition, she said, because different studies might use different types, doses, and applications of cannabis, they’re difficult to compare.
A large body of evidence around cannabis and pain available to clinicians, Fitzcharles said, is anecdotal—which might bias physicians and patients to thinking that cannabis is more effective than it actually is. “As clinicians, we hear some patients having reportedly outstanding effects,” she said. “Those very positive responses stand out in our minds. We’re programed to look at success.” But we don’t know how many of those patients are experiencing a placebo effect, she said. “We also see patients who report significant adverse effects, or no effects at all.”
Supporting patients who use cannabis
Regardless of the research available on cannabis and joint pain, patients are taking advantage of the accessibility of the drug. In the United Kingdom, 21% of medical cannabis users took the drug for arthritis, according to a 2005 study of nearly 3000 patients.6 A study published that same year out of Australia found 35% of medical cannabis users had arthritis.7 A 2018 study8 of cannabis users found that, of more than 2000 patients, just under 10% had arthritis which supported the findings of a 2015 study9 that found around the same percentage of California medical cannabis users. Indeed, arthritis is one of the most commonly reported conditions patients treat with cannabis.10
However, many physicians working with patients who are using or interested in using cannabis for arthritis or joint pain are unfamiliar or uncomfortable discussing the drug. In 2014, a survey of the Canadian Rheumatology Association found that more than three quarters of the respondents said they did not feel confident about their knowledge of cannabinoids and the endocannabinoid system.11 In addition, the respondents were divided on their view of the usefulness of cannabis: half believed there was no role for cannabinoids in the diseases that they treated.
“I think in the rheumatology community there are two diametrically opposed camps,” Fitzcharles said. “There’s very little in the middle. There is a group of physicians that have said, ‘opioids are out and cannabinoids are in.’ And at the opposite end of the spectrum are people saying, ‘I don’t want to go there, I don’t think it’s good.’ There’s tremendous uncertainty, and tremendous polarization.”
The environment around cannabis has changed rapidly, and physicians might feel insecure about their limited knowledge of the drug, Fitzcharles says. She’s optimistic, though, that the changes in legal status will open up the conversation in the medical setting. “People are discussing it with their physicians,” she said.
Miller said that he thinks cannabis is a promising enough treatment that patients who are interested should try and see if it works for them. “Arthritis, like any other disease, is heterogeneous,” he said. “I would think it’s a pretty good thing to try if you’re suffering.”
Doctors and clinicians might also have to reframe expectations around the standard of evidence that will be available on cannabis because of the challenges associated with conducting gold-standard, randomized clinical trials. “We might have to rethink how we accumulate data, and might have to use observational studies. But we can’t just use individual patient anecdotes,” Fitzcharles said.
For now, the approach in the clinic should be toward harm reduction, she said. “We need to know the reasons a person is using the drug and look at the other drugs that they’re using.” They might turn to cannabis because they have side effects of opioids, or because they prefer the perception of a more natural drug treatment, she said.
It’s also important to determine who clinicians should recommend not use cannabis or cannabinoid products, Fitzcharles said. For example, she would not recommend that anyone under the age of 25 use the drug to treat a rheumatoid condition. “There’s also a big concern about the elderly, and studies have not been done in that patient population,” she said.
Doctors also should note possible interactions with other psychoactive medications that a patient is taking, that might heighten the side effects that come from cannabis. “Patients need to be functional,” Fitzcharles said. “Patients with rheumatoid disease want to be functional. How are you functional in the Western world? You drive a car. The risks of driving are really, really important.”
The most important thing clinicians can do, though, is listen to and have an open conversation with patients around their potential cannabis use, she said. “I use the word empathy repeatedly. It’s an open, empathetic conversation. We really have to reassure the patient we are there for their total care.”
- Habib AM, Okorokov AL, Hill MN, et al. Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. Br J Anaesth. 2019;S0007-0912(19)30138-2.
- Barrie N, Kuruppu V, Manolios E, et al. Endocannabinoids in arthritis: current views and perspective. Int J Rheum Dis. 2017;20:789-797.
- Krustev E, Reid A, McDougall JJ, et al. Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints. Arthritis Res Ther. 2014;16:437.
- Blake DR, Robson P, Ho M, et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45:50-2.
- Fitzcharles MA, Ste-Marie PA, Häuser W et al. Efficacy, tolerability, and safety of cannabinoid treatments in the rheumatic diseases: a systematic review of randomized controlled trials. Arthritis Care Res (Hoboken). 2016;68:681-688
- Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. 2005;59:291-295.
- Swift W, Gates P, Dillon P. Survey of Australians using cannabis for medical purposes. Harm Reduct J. 2005;2:18.
- Baron EP, Lucas P, Eades J, et al. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. J Headache Pain. 2018;19:37.
- Park JY, Wu LT. Prevalence, reasons, perceived effects, and correlates of medical marijuana use: s review. Drug Alcohol Depend. 2017;177:1–13.
- Salazar CA, Tomko RL, Akbar SA, et al. Medical cannabis use among adults in the Southeastern United States. Cannabis. 2019;2:53–65.
- Fitzcharles MA, Ste-Marie PA, Clauw DJ, et al. Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints. BMC Musculoskelet Disord. 2014;15:258.