Cannabis-based drug shows some benefits in RA

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Cannabis-based drug shows some benefits in RA



Jan 23, 2006



Zosia Chustecka

Bath, UK - The cannabis-based drug Sativex (GW Pharmaceuticals) has

shown some benefits in rheumatoid arthritis (RA) in the first-ever

controlled trial conducted in this patient population. The company-

funded study, conducted in 58 patients, is published in the January

2006 issue of Rheumatology [1]. The researchers describe the results

as " encouraging " and say larger and more prolonged studies are

warranted.

The product used in the trial is commercially available as a

prescription medicine, but so far only in Canada. Sativex was

launched there last year for use as an adjunctive treatment for

symptomatic relief of neuropathic pain in adults with multiple

sclerosis. It is awaiting approval in the UK, although the regulatory

authority has said that further clinical data are required. The

product is cannabis-derived but is not psychoactive and comes in the

form of an oromucosal spray composed primarily of

tetrahydrocannabinol (THC) and cannabidiol (CBD), according to the

company.

Small but significant effects

Dr Blake (Royal National Hospital for Rheumatic Diseases, Bath,

UK) and colleagues tested Sativex for the relief of pain in RA over a

five-week period. Patients had active RA not adequately controlled by

standard medications, with " disease of extended duration and . . .

poor analgesic control, " the researchers comment. Patients continued

to take stable doses of the drugs they were already using

(nonsteroidal anti-inflammatory drugs [NSAIDs], disease-modifying

antirheumatic drugs [DMARDs], and prednisolone). They began adding

the new product with one actuation at bedtime and then gradually

increased the dose to a maximum of six actuations per day.

The primary efficacy was pain on movement, measured each morning on a

numerical rating scale (0-10). A significant difference was found

between the Sativex and placebo groups. Statistically significant

differences were also measured on several secondary efficacy end

points, including pain at rest, quality of sleep, and the disease

activity score (DAS28). Patients were also assessed on the Short-Form

McGill Pain Questionnaire (SF-MPQ); one of three of these assessments

(pain at present) showed a significant difference between the two

groups, but the other two (total intensity of pain and intensity of

pain at present) did not. There was no effect on morning stiffness,

but the baseline scores were " surprisingly low, " the researchers

comment.

Results before and after a five-week treatment period with the

cannabinoid-based drug Sativex



Efficacy measure

Sativex baseline

Sativex end point

Placebo baseline

Placebo end point

p*

Morning pain on movement

7.0

4.8

6.7

5.3

0.044

Morning pain at rest

5.3

3.1

5.3

4.1

0.018

Morning stiffness

3.5

3.0

3.8

3.2

0.454

Quality of sleep

5.7

3.4

5.8

4.6

0.027

DAS28

5.9

5.0

6.0

5.9

0.002



*difference between drug and placebo

To download table as a slide, click on slide logo below

The suppression of pain on movement, the primary end point, suggests

a peripheral analgesic action, Blake et al write; the suppression of

pain at rest suggests a more central effect. In addition, the " modest

suppression of the present gold-standard inflammation-activity

measure, the DAS28, might indicate an influence on the immune

effector system. The improvement on sleep, a relevant clinical bonus,

was probably due mainly to nocturnal symptom relief rather than a

specific hypnotic effect, since this was not observed in a sleep-

laboratory study of the compound at this dosage. "

The product was well tolerated, the researchers comment. The most

commonly reported adverse events were dizziness (eight patients on

Sativex vs one on placebo), light-headedness (three vs one), dry

mouth (four vs zero), and nausea (two vs one).

Blake and colleagues comment that although the differences that were

seen between product and placebo were " small and variable across the

population, they represent benefits of clinical relevance and

indicate the need for more detailed study. "

Cannabis has a long history of being used—unofficially—to help

with medical symptoms, and a recent UK survey showed that arthritis

(type not specified) was the fifth most common reason for such use,

after multiple sclerosis, neuropathy, chronic pain, and depression,

they note.

Cannabinoid receptors involved in bone

Separately, new research has unearthed the finding that certain

cannabinoid receptors are involved in maintaining normal bone

density, a discovery that opens up a new approach for the treatment

of osteoporosis [2]. Cannabinioids interact with two receptor types—

CB1, found in the central nervous system and responsible for the

psychoactive effects of these compounds, and CB2, about which little

was known until now. A team of scientists from Bonn University

(Germany) and the Hebrew University (Jerusalem, Israel) has shown

that these CB2 receptors are located on the surface of both

osteoblasts and osteoclasts and are involved in maintaining normal

bone density. Genetically engineered mice lacking the CB2 receptor

developed osteoporosis as they aged, the researchers report, and

women who carry a specific variant of the CB2 gene have a threefold

higher risk of developing osteoporosis. Studies of mice that had

their ovaries removed showed that a compound active at the CB2

receptor can " diminish the bone loss caused by ovary removal, " the

researchers report, which opens up a novel therapeutic avenue.

http://www.jointandbone.org/viewArticle.do?primaryKey=633031