A marijuana breakthrough?

A DECADE ago, when Daniele Piomelli went to scientific conferences, he was often the only researcher studying cannabinoids, the class of chemicals that give marijuana users a high. His work often drew sniggers and jokes; but not any more. At the recent annual Society for Neuroscience conference in San Diego last week, scientists delivered almost 200 papers on the subject.

Why all the attention? Many scientists believe marijuana-like drugs might be able to treat a wide range of diseases, far beyond the nausea and chronic pain typically treated with medical marijuana.

Researchers presented tantalising evidence that cannabinoid drugs can help treat amyotrophic lateral sclerosis - known as ALS or Lou Gehrig’s disease - Parkinson’s disease and obesity. Other researchers are studying whether the compounds can help victims of stroke and multiple sclerosis.

Although the chemicals work on the same area of the nervous system, the new drugs are much more refined and targeted than marijuana, with few of its side effects.

"Cannabinoids have a lot of pharmaceutical potential," says Piomelli, a neuroscientist at the University of California. "A lot of people are very excited."

Although the US government opposes the use of medical marijuana, it generally doesn’t restrict cannabinoid research, most of which doesn’t involve the cannabis plant itself. Scientists who use Marinol, a legal but tightly regulated marijuana-like drug, do need government permission.

Because the cannabinoid system wasn’t discovered until the late 1980s - decades after serotonin, dopamine and other neurotransmitters - researchers still know relatively little about how it works.

Like all neurotransmitter networks, the cannabinoid system consists of a series of chemical pathways through the brain and nervous system. Marijuana produces its effects by activating this pathway, primarily through the effects of tetrahydrocannabinol (THC), the drug’s active ingredient.

Over the past decade, researchers have been following these abundant trails to determine their real purpose. "You don’t have them there to get stoned. So there must be internal reasons," says Andrea Giuffrida, a neuroscientist at the University of Texas.

Researchers have learned that endogenous cannabinoids - internal brain chemicals that activate the system - play a role in tissue protection, immunity and inflammation, among other functions. The cannabinoid system also appears to exert wide influence, modulating the release of dopamine, serotonin and other neurotransmitters.

Giuffrida and others believe cannabinoids can treat degenerative disorders such as Parkinson’s disease and ALS. At the conference, Giuffrida announced that a cannabinoid drug wards off Parkinson’s-like effects in mice. The disorder destroys neurons in a key part of the brain, causing patients to lose control over movement.

Giuffrida injected mice with a chemical called MPTP, which mimics Parkinson’s damage. When some of the animals subsequently received a drug that affects cannabinoid receptors, their nerve cells suffered far less damage than did the cells of the other mice. This was the first demonstration that a cannabinoid drug can have this effect.

While he is not sure how the anti-cannabinoid compound works, Giuffrida suspects it protects neurons by reducing inflammation, a key component in Parkinson’s. Cannabinoids might also slow down ALS, which destroys neurons that control muscles until victims become paralysed, unable to breathe on their own.

Neuroscientist Mary Abood first became interested in cannabinoids after hearing about ALS patients who got some relief from smoking marijuana.

In her study, mice with a variant of ALS were given a combination of THC and cannabidiol, another compound found in marijuana.

Both substances are cannabinoid agonists, chemicals that activate the cannabinoid system.

Abood measured the course of the ailment by testing how long the mice could stand on a slowly rotating rod.

The treatment delayed disease progression by more than seven days and extended survival by six days. In human terms, this would amount to about three years. That’s a significant improvement over the only existing ALS drug, riluzole, which extends life by two months.

Also at the conference, researchers at the Institute of Neurology in London announced results that corroborated her findings. Cannabinoids have also helped some human ALS patients in one small trial and Abood is trying to get funding for a larger one.

If cannabinoids can shield human neurons from harm, researchers say, they might prove useful against other neurological diseases, including mental illness. Scientists are also looking at whether cannabinoids can help treat multiple sclerosis, epilepsy and Huntington’s disease, while Giuffrida is beginning a study of their effect on schizophrenia.

Advocates of medical marijuana have long argued the drug can be useful for treating conditions such as chronic pain, nausea and glaucoma.

Some researchers, however, believe there are better, more precise ways to stimulate the cannabinoid system. They believe marijuana has too many negatives to be a truly effective drug, with side effects that include memory problems, decreased immunity and possible addiction.

Marijuana has another drawback. From a scientific standpoint, Giuffrida says, it’s "a very dirty drug". It contains more than 300 compounds, 60 of which affect the cannabinoid system, which makes it difficult for researchers to accurately pinpoint marijuana’s effects.