The discovery of cannabinoid CB 1 and CB 2 receptors (1, 2) and endogenous agonists (3) for these receptors has renewed the scientific community’s interest in their therapeutic value as analgesics and for various conditions, including migraine headaches, nausea and vomiting, wasting syndrome and appetite stimulation in HIV-infected patients, muscle spasticity due to multiple sclerosis or spinal cord injury, movement disorders such as Parkinson disease, epilepsy and glaucoma (6).

Two major factors should be taken into account in any suggested therapeutic indication: the adverse effects of the treatment and its effectiveness compared with that of existing alternatives. Independently of scientific developments, an aggressive debate about the therapeutic use of cannabinoids, including demands for their more liberal availability (4, 5) has been ongoing. Two systematic reviews have been undertaken to shed light on the therapeutic potential of cannabinoids: firstly for the management of pain (7) and secondly for nausea and vomiting induced by chemotherapy (8). In the first review, all randomized controlled trials which compared the efficacy and safety of cannabinoids with those of conventional analgesics (7) were examined. Nine trials involving 222 patients, of whom 128 had cancer, chronic malignant pain, and postoperative pain showed that cannabinoids were no more effective than codeine in controlling acute and chronic pain and they had undesirable effects in depressing the central nervous system. However, these studies are mostly from the 1970s and use of nonsteroidal anti-inflammatory analgesics alone or in combination with opioids is now common. As such, cannabinoids for these indications is no longer required (9).

In chronic non-cancer pain, however, more effective analgesics are needed, although it is difficult to believe that the anti-inflammatory effects of cannabinoids would be superior to other drugs available now. Neuropathic pain may be one area where cannabinoids could have potential.

The second review analysed the effectiveness of cannabinoids in chemotherapy induced nausea and vomiting amount 1366 patients in 30 randomized controlled trials (8). Across all trials, cannabinoids showed some anti-emetic efficacy compared with active comparators and placebo. In highly emetogenic settings, however, they did not show any efficacy. Most of the studies analysed were conducted in the 1980s before the serotonin receptor antagonists were introduced and changed the practice of anti-emesis in chemotherapy induced nausea and vomiting (9).

Future research may provide better cannabinoid compounds with potential new applications but the current information is that the adverse effects outweigh effectiveness. On current evidence, cannabinoids can be recommended only for use in controlled clinical trials in carefully selected conditions. The first large multicentre trial on cannabis in the control of pain and tremors in multiple sclerosis is a good first step (10).

References

1. Marsuda, L.A., Lolait, S.J., Borwnstein, M.J. et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346: 561 - 564 (1990).

2. Munro, S., Thomas, K.L., abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365: 61 - 65 (1993).

3. Mechoulam, R., Ben-Shabat, S. Hanus, L. et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemistry and Pharmacology, 50: 83 - 90 (1995).

4. Kassirer, J-P. Federal foolishness and marijuana. New England Journal of Medicine, 336: 366 - 367 (1997).

5. Bosch, X. Catalan Parliament pushes for legalization of cannabis as therapy. British Medical Journal, 325: 511 (2001).

6. British Medical Association. Therapeutic uses of cannabis. London: BMA, 1997.

7. Campbell, F.A., Tramer, M.R., Carroll, D. et al. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. British Medical Journal, 323: 16 - 21 (2001).

8. Tramer, M.R. Carroll, D, Campbell, F. et al. Cannabinoids for the control of chemotherapy induced nausea and vomiting: quantitative systematic review. British Medical Journal, 323: 16 - 21 (2001).

9. Editorial. Cannabinoids for pain and nausea. British Medical Journal, 323: 2 - 3 (2001).

10. Dyer, O. Cannabis trial launched in patients with MS. British Medical Journal, 322: 192 (2001).