“Joints for Joints.” That was the title of a lighthearted yet science-based debate at the annual scientific meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals in 2011. The topic: whether medical marijuana – that is, the medicinal use of the cannabis plant – was a safe and effective arthritis treatment.

Taking the “con” view, Stuart L. Silverman, MD, attending physician at Cedars-Sinai Medical Center in Beverly Hills, Calif., argued that although some cannabis research was compelling, inconsistent dosing and quality-control issues, as well as a lack of well-controlled research, meant marijuana was not “ready for prime time,” particularly where arthritis was concerned.

Taking the “pro” position, Arthur Kavanaugh, MD, a professor of medicine at the University of California, San Diego (who declined to be interviewed for this article), argued that the type of carefully controlled trials Dr. Silverman called for had not been conducted on aspirin, either, and that cannabis – used medicinally for nearly 5,000 years – had few side effects, eased pain from rheumatoid arthritis (RA), and might reduce inflammation as well.

Drs. Silverman and Kavanaugh didn’t reach any firm conclusions, but after multiple rheumatologists in the audience revealed that many of their patients were inquiring about or already using cannabis, one thing was clear: Medical marijuana had gone mainstream.

In fact, 18 states and Washington, D.C., have legalized limited use of medical marijuana for certain conditions. (Some, including California, permit it for arthritis; others, such as New Jersey, do not.) Two states, Washington and Colorado, have decriminalized even its recreational use. A 2011 Journal of Pain survey revealed that almost 10 percent of Americans with chronic pain use marijuana. Although it’s unclear how many of those have arthritis, large-scale surveys from the United Kingdom and Australia indicate that roughly one-third of people who use medical marijuana do so for arthritis – and most report considerable pain relief. Additionally, a Canadian study in Arthritis Care & Research found that among 457 patients with fibromyalgia, 13 percent used cannabis to manage their disease.


How It Works

Research shows that, among other things, cannabis eases chemotherapy-induced nausea and loss of appetite, and relieves spasms in individuals with multiple sclerosis. Even so, pain relief is perhaps the most well-recognized and studied effect.

Several decades ago, scientists discovered that mammals, including humans, have a pain-regulating system (the endocannabinoid system) with receptors in nervous system tissue, immune cells and bone and joint tissue. These receptors respond to cannabinoids, a set of compounds that include endocannabinoids, which the body creates on its own; and phyto-cannabinoids, plant-based compounds found in marijuana that are very similar to endocannabinoids.

The best known cannabinoids are THC (delta-9-tetrahydrocannabinol, the psychoactive compound in cannabis) and CBD (cannabidiol, a major constituent of the plant thought to act as a sedative and reduce inflammation, nausea and convulsions). They have complex mechanisms, but in a nutshell, cannabinoids can reduce pain by acting on certain receptors.

Of the two main cannabis species – sativa and indica – sativa contains higher THC and lower CBD levels and produces a more euphoric “high.” Indica has higher CBD and lower THC levels and is used to aid sleep and ease pain.

Cannabinoids also seem to have a positive impact on some other pain medications. One study, in Clinical Pharmacology & Therapeutics in 2011, found that chronic pain patients using long-acting oxycodone or long-acting morphine who inhaled vaporized herbal cannabis experienced a significant decrease in pain – far more than with the opioids alone. Though the study was of just 21 patients, study author Donald I. Abrams, MD, professor of clinical medicine at the University of California, San Francisco, says it “suggests that cannabis has the potential to relieve pain and decrease use of opioids, which, unlike cannabis, are associated with major side effects.”


 

Evidence for Arthritis

Studies show it can be somewhat effective in treating pain from arthritis and related conditions. One meta-analysis of four randomized trials published as an abstract in the Annals of the Rheumatic Diseases, found that oral cannabinoids (cannabis oil) offered minimal to moderate improvement compared with placebo in individuals with musculoskeletal pain, including RA, back pain and fibromyalgia. Study author Janet Pope, MD, professor of medicine at the University of Western Ontario in Canada, notes that the results are not generalizable to smoking marijuana, and says, “The benefit was modest, and this was only studied for short periods of time.”

A 2011 British Journal of Clinical Pharmacology review examined 18 studies of smoked, oral and/or synthetic cannabis and concluded cannabis was safe and modestly effective in neuropathic pain (chronic pain that results from damaged or dysfunctional nerve fibers), and also had the potential to help treat RA and fibromyalgia pain. Additionally, cannabis has been shown to improve sleep – and a lack of sleep is known to exacerbate general pain and arthritis symptoms.

And cannabis holds promise for osteoarthritis (OA). “Joints have a complex endocannabinoid system and are able to produce their own endocannabinoids. But in disease states, such as with osteoarthritis, these endocannabinoids are broken down too quickly, so they can’t help with joint pain,” says Jason J. McDougall, PhD, associate professor in the departments of pharmacology and anesthesia at Dalhousie University in Halifax, Nova Scotia. In ongoing animal research, McDougall and his colleagues have found that by blocking certain enzymes or injecting cannabinoids into the joint, sensitivity and pain are reduced, leading McDougall to speculate that both endocannabinoid-targeting and cannabis-based treatments may hold new hope for individuals with OA.

Cannabis also may ease inflammation and affect immunity. In-vitro and animal studies have shown that both herbal and synthetic cannabinoids have the ability to suppress inflammation. Most recently, a Biological & Pharmaceutical Bulletin study in 2011 revealed that six different cannabinoids inhibited the activity of COX-2 enzymes, which play a role in arthritis-related inflammation. Other preliminary studies suggest cannabinoids may have immunosuppressive properties – including the ability to inhibit pro-inflammatory molecules called cytokines.

Why Docs Worry

Put simply, when you use herbal cannabis – that is, you inhale or ingest the marijuana plant in some form – you can’t be sure of what you’re getting. Cannabis contains hundreds of compounds, about 60 of them with cannabinoid properties. “But every plant contains different concentrations, so [using marijuana] is not the same as taking a carefully calibrated medication,” says Mary-Ann Fitzcharles, MD, associate professor of medicine in the department of rheumatology and pain management unit at McGill University in Montreal. She is considered one of the foremost experts on the use of cannabis in arthritis and fibromyalgia. In addition, she says, “There are no well-controlled studies on humans using herbal cannabis for arthritis. The few that exist are relatively small, and long-term effects are unknown.”

If you do obtain a prescription from a physician, you get your medication not at a pharmacy, but at a marijuana collective or dispensary – where the choices can be confusing at best, says Dr. Silverman. “You have a menu offering names like Blue Kush and Green Haze, which don’t necessarily tell you which kind of marijuana – indica, sativa or hybrid – it is. And not all list the potency – for example, 13 percent THC – or have been screened for fungus or pesticides. If you’re not familiar with marijuana, how do you know how much or which kind to use?”

Dr. Silverman says that most rheumatologists are not informed or prepared to give specific advice on how to use medical marijuana, “so you’re forced to rely on the advice of the person behind the dispensary counter,” he notes.


 

Dr. Abrams disagrees. “I’m a cancer doctor, not a rheumatologist, but most dispensaries in California, where I live, tell you whether you’re getting indica or sativa, as well as the percent of THC it contains,” he says. “And the bottom line is, marijuana is a very safe drug. When we give patients with chronic pain a prescription for gabapentin [a drug often used as a painkiller], we say, ‘Start with one; try two or three if that doesn’t work.’ It’s the same with medical marijuana: Start low and see how it goes.”

In addition, says Dr. Abrams, “As an oncologist, I see patients who have extreme pain, depression and nausea. I feel comfortable being able to recommend one ‘medication’ – a medication they can even grow themselves, which is very empowering – with few side effects, rather than multiple prescriptions for medications with severe side effects.”

In fact, Dr. Pope’s study found that the most common side effects of oral cannabinoids were drowsiness and confusion, and marijuana is not known to have negative interactions with medications used for RA, OA or most other musculoskeletal or rheumatic diseases. However, says Dr. Fitzcharles, “My research has shown that it is associated with anxiety in individuals with fibromyalgia. And because THC concentrations are so much higher than they used to be even 10 years ago, it is a known cause of acute psychotic episodes in Canadian emergency rooms.”

THC potency now can be greater than 20 percent – 10 times higher than in the 1960s and ’70s, Dr. Silverman adds.

Even so, many medical marijuana users with chronic pain say they don’t experience the “high” recreational users do – which some experts say may be due to complications in nerve signaling. Plus, medical marijuana users can choose specific strains with low concentrations of THC, adds Dr. Abrams.

Bottom Line

Every expert interviewed for this story expressed enthusiasm over research on cannabis and arthritis – and cautioned that the best options for most people are treatments with a proven track record.

“There’s no question that cannabinoids have the potential to have an impact on the disease,” says Dr. Fitzcharles. Even so, she adds, “I think to turn to something with very little evidence – and so much potential to have negative impact – is dangerous.”

Proven, effective treatments are already available for RA, OA and diseases like lupus, says Dr. Pope. But, she says, “We do need better treatments.”

Patients with chronic musculoskeletal pain have an unmet need for pain relief, given that existing medications, especially narcotics, have side effects that include addiction and impairment. Cannabis may come to fill the gap.

For now, however, “Medical marijuana is uncharted territory,” says Dr. Silverman. “So buyer beware.”

Camille Noe Pagán is a contributing editor to Arthritis Today.

For the full article, see the May/June 2013 issue of Arthritis Today.