LONDON ¿ The question of whether smoking cannabis relieves some of the symptoms of multiple sclerosis (MS) has been the subject of a long-running debate. Now a scientific study has proved that cannabinoids, which are among the active compounds absorbed from cannabis smoke, can reduce muscle tremor and rigidity in a mouse model of MS.

David Baker, head of the Neuroinflammation Group at the Institute of Neurology in London, said the studies showed that cannabinoids were able to significantly reduce symptoms in the mice and that the effect lasted for several hours. He added, ¿Although not a cure, our research suggests that cannabinoids can play a crucial role in controlling some of the neuromuscular problems seen with MS.¿

Baker and his colleagues believe that the cannabinoids resemble compounds produced naturally in the body that regulate and control muscle tone. The group suggests the latest finding may allow the identification or development of drugs to treat some of the symptoms of MS.

The Multiple Sclerosis Society of Great Britain and Northern Ireland, which supported the study, said the results provide a ¿compelling explanation¿ of why some people with MS perceive benefits from using cannabis. Lorna Layward, head of research at the MS Society and a co-author of the study, said, ¿For some years there has been anecdotal evidence that some people with MS have found relief from symptoms such as painful spasms by using cannabis. This research sets that evidence into context.¿

The study, which is reported in the March 2, 2000, issue of Nature, in a paper titled ¿Cannabinoids control spasticity and tremor in a multiple sclerosis model,¿ will now provide ¿a firm basis,¿ Layward said, ¿for the human trials of cannabis in MS that will commence shortly.¿

Patients with MS from across the UK already are being recruited into a trial to evaluate the therapeutic effects of cannabis extract. The study, by John Zajicek, a consultant neurologist at Derriford Hospital in Plymouth, UK, is expected to involve more than 600 patients with significant spasticity in their leg muscles.

Those taking part will be allocated at random to treatment with capsules containing either extract of cannabis, or tetrahydrocannabinol (a constituent of cannabis, and the active ingredient in marijuana), or a placebo containing only a vegetable oil. The trial will be double-blind and will take three years to complete.

A spokeswoman for the Medical Research Council, which is funding the clinical trial with a grant of #950,000, told BioWorld International: ¿Given these latest scientific results, it makes it even more important now to get on with the human studies.¿ The MS Society is also supporting the Plymouth study.

Multiple sclerosis is the most common neurological disease affecting young adults in the Western world. An estimated 85,000 people in the UK suffer from the disease, in which nerve fibers in various parts of the body lose their insulating layer of myelin. The symptoms include muscle stiffness and spasticity, pain, fatigue, difficulty in passing urine, and tremors.

Baker, first author of the Nature paper, together with colleagues from the National Hospital for Neurology and Neurosurgery in London, the University of Aberdeen in Aberdeen, UK, and the MS Society, designed a study to try to evaluate the effect of cannabis on some of these symptoms using a mouse model of MS. These mice develop spasticity and tremor following induction of a syndrome called chronic relapsing experimental allergic encephalomyelitis.

Cannabis is known to act through receptors called CB1 and CB2. The CB1 receptor is found in the central nervous system (CNS) and in many peripheral tissues. The CB2 receptor is found on white blood cells; some studies have also shown that it is expressed at low levels in the brain.

The group found that when they gave the mice synthetic cannabinoid compounds, symptoms of tremor and spasticity faded rapidly and took several hours to return. Other experiments, which involved blocking either the CB1 receptor or the CB2 receptor, caused an increase in symptoms, which would suggest that both receptors are involved in regulating muscle tone in these mice, the researchers say.

In the conclusion of their paper, Baker and his colleagues write: ¿There is a need for more effective oral or systemic anti-spasticity agents. The hydrophobic nature of cannabinoids allows their rapid access to the CNS. The data presented here provide evidence for the rational assessment of cannabinoid derivatives in the control of spasticity and tremor in MS, in placebo-controlled trials.¿