BioWorld International Correspondent

LONDON - New drugs might be available for the treatment of atherosclerosis in eight years, said researchers who have discovered that a derivative of cannabis can prevent atherosclerosis from building up in the blood vessels of mice.

The European team behind the research said that receptors that interact with some of the active ingredients of cannabis might be "valuable clinical targets for treating atherosclerosis."

Francois Mach, professor in the division of cardiology at Geneva University Hospital, told BioWorld International: "The importance of this discovery has less to do with cannabis than with the fact that it opens up an entirely new area of research in cardiovascular biology, into how we can modulate these receptors that interact with derivatives of cannabis."

He and his colleagues now are designing experiments to establish ways of regulating the receptors, which are found on cells of the immune system.

A report of the study appears in the April 7, 2005, issue of Nature in a paper titled "Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice."

Yet anyone seeking to justify their marijuana habit by saying it will prevent heart disease is being hasty. Commenting on the paper in a "News and Views" article in the same Nature issue, Michael Roth, of the department of medicine at the University of California at Los Angeles, wrote that the findings "are striking, but they should not be taken to mean that smoking marijuana is beneficial for the heart."

The main active ingredient of marijuana is a cannabinoid derivative called delta-9-tetrahydrocannabinol (THC). It binds to two types of receptors, CB1 and CB2. CB1 is found mainly in the brain. CB2 is present solely on cells outside the nervous system and especially on the cells of the immune system.

Numerous studies have shown that cannabinoids such as THC can have immunosuppressive and anti-inflammatory effects, which might be useful in treating autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. A previous study by another team showed that the cannabinoid derivative, cannabidiol, was able to reduce inflammation by inhibiting T-helper cells in a mouse model of rheumatoid arthritis.

Mach and his colleagues decided to investigate how THC might influence the inflammatory process that occurs in atherosclerosis. In that disease, fatty deposits called plaques build up in the arteries, with inflammation playing a part in the processes of plaque rupture and thrombosis.

The team's first major finding was to establish that the CB2 receptor is present in atherosclerotic plaques in arteries from humans and mice, but not in healthy arteries.

The researchers then found that an oral dose of 1 mg per kilogram of body weight daily of THC significantly slowed the progression of disease when given to animals with advanced atherosclerosis, compared to controls (p<0.05). The effect was less pronounced at both higher and lower doses.

Normally during the development of atherosclerosis, white blood cells stick to the inside of the blood vessel wall. Mach and his colleagues used live microscopy of the blood vessel lumen wall to observe that significantly fewer white blood cells stuck to it in animals treated with THC than in controls (p<0.05). But it did not happen in the presence of an antagonist specific for the CB2 receptor.

Mach said: "We have several studies lined up for the future. We would like to define ligands that will act only on the CB2 receptor and not on the CB1. We want to find out exactly what CB2 is doing and what it interacts with. We also want to know if we can prevent the development of atherosclerosis by giving THC to the susceptible mice as soon as we start them on a high-fat diet. We also suspect that if we give the antagonist for CB2 to the mice, they may develop an even greater degree of atherosclerosis. If they do, this will suggest that there are natural ligands that bind to CB2, and perhaps the levels of these vary in people with differing susceptibility to atherosclerosis."