Marijuana Extract for Arthritis Pain

November 12, 2005

Sativex, an oral spray containing marijuana extracts, has been shown to relieve pain associated with rheumatoid arthritis (RA), according to a new British study. The researchers also report that the study participants did not experience "highs" typically achieved by smoking marijuana.

The study, by DR Blake et al, was published in Rheumatology Advance Access online on 9 November 2005 and reported on the same day by MedPage Today.

"Anecdotally, of course, people have been using it for centuries," said Candy McCabe, PhD, of the Royal National Hospital for Rheumatic Diseases here, according to MedPage Today. "We've known in our clinic that patients are using street-based cannabis."

Cannabis was first proposed as a useful analgesic for a spectrum of rheumatic diseases in 2800 BC, according to the researchers. By 1997 the British Medical Association had concluded that herbal cannabis was unsuitable for medical use. Clinical trials have produced equivocal results, which may in part be caused by the chemical complexity of cannabis, which contains hundreds of different compounds, many of which interact, with additional synergistic or antagonistic effects.

About Sativex

Sativex contains a blend of whole-plant extracts. Its two key ingredients, present in approximately equal amounts, are delta-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC and CBD have been shown to have beneficial effects for RA in animals. Minor cannabinoids, including cannabinol, cannabichromene and cannabigerol are also present in trace quantities.

Sativex is manufactured by GW Pharmaceuticals of Salisbury, England. The Canadian product information for Sativex, from Bayer Health Canada, is available here.

Sativex is not approved in Britain or the US. It was licensed in early 2005 in Canada for use in patients who have neuropathic pain associated with multiple sclerosis. Sativex is also being tested for use in patients with cancer pain.

The Clinical Trial

Sativex underwent clinical testing in a multi-center, randomized, placebo-controlled trial of 58 patients over five weeks. The investigators claim that this was the first formal study that uses cannabis-based drugs to treat RA.

Study participants with active RA not adequately controlled by standard medication were randomized to receive either Sativex (by oral spray -each dose delivering THC and CBD or placebo.

Dosing started with one use of the oral spray one-half hour before bedtime and increased to a maximum of six doses per day, depending on individual response. All dosing occurred during evening hours.

The primary efficacy measure was morning pain on movement, judged on a scale of 1 to 10. Secondary efficacy measures were morning pain at rest, morning stiffness, sleep quality, the Short-Form McGill Pain Questionnaire (SF-MPQ) and the 28-joint disease activity score (DAS 28).

Primary efficacy variable was pain on movement measured by a 0-10 numerical rating scale (NRS) each morning. Secondary outcomes included NRS measures of pain at rest, sleep quality and morning stiffness, the Short-Form McGill Pain Questionnaire (SF-MPQ) and the 28-joint disease activity score (DAS28).

Trial Results

Researchers found that, for participants receiving Sativex, pain on movement in the morning and pain at rest decreased significantly, compared with placebo. However, no significant difference was observed in morning stiffness.

Participants receiving Sativex experienced significantly improved quality of sleep, and their DAS28 scores also significantly improved.

The SF-MPQ showed that the Sativex group rated their pain as significantly less intense than did the placebo patients, but on two other points of the questionnaire, no significant difference was noted.

Interpretation of Results

The researchers described the effects on pain as "small and variable across the population; but they represent benefits of clinical relevance." They also noted that the beneficial effects occurred when participants received evening doses only, and benefits may have been greater with 24-hour usage.

Authors Blake et al summarized their findings by saying, "Whilst the differences are small and variable across the population, they represent benefits of clinical relevance and indicate the need for more detailed study of dosage, formulation and ideal patient subgroup."

"Most important, the quality of sleep was improved, which we know in patients makes a big difference in how they perceive their pain the next day. It's a very fatiguing disease," commented co-author CS McCabe, according to MedPage Today.

Dr McCabe noted that the improved sleep seemed not to be caused by intoxication by the drug. "They were getting the effect without feeling high," she said to MedPage Today.

Another co-author, Ronald Jubb, MD, a rheumatologist at the University Hospital Birmingham NHS Foundation Trust, reportedly said that abuse of the medication seems to be "a very rare event."

"The motivation of medicinal users of cannabis-based medicine is entirely different from recreational users," Dr Jubb told MedPage Today. "The former simply want symptom relief and the ability to go about their normal lives, and for them intoxication would be a distinct disadvantage; for the latter, smoking marijuana is infinitely more intoxicating than Sativex."

According to Dr McCabe, the study was mainly intended to examine tolerance, to establish the severity and types of adverse events, as well as the risk of intoxication. Results showed that adverse events were mild to moderate and included mild dizziness; no treatment-related withdrawals or serious adverse events occurred in the group receiving the drug.

No indication of intoxication arose, either. "The patients' perception was that this was a drug that was going to get them high, but we didn't find that," Dr McCabe commented, noting that the next step would be a larger study in the same patient-population.

Sources:
Cannabis-Based Drug Relieves Arthritis Pain, MedPage Today, 9 November 2005.
Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis, Blake DR et al, Rheumatology Advance Access, published online 9 November 2005.

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