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Can Marijuana Chemicals Make Good Medicine?
Nicholas Bakalar | National Geographic | 10/13/2005

Researchers are finding promising new evidence of the medicinal benefits of cannabinoids, the active ingredient in marijuana. But don't expect packages of pot to turn up on pharmacy shelves just yet.

Today a team of international researchers announced the discovery of CB2, the second cannabinoid receptor found in mammal brains.

Unlike the first receptor, discovered 15 years ago, CB2 activation reduces nausea without producing psychotropic side effects.

The new receptor is activated by endocannabinoids, which are cannabis-like chemicals produced in nerve cells and certain other cells in the body.

The team reports the findings in today's issue of the journal Science.

The Body's Own Cannabinoids

Cannabinoid receptors have been found in the brain, nervous system, spleen, thymus, and in various circulating immune cells.

Establishing the presence of the receptors in the brain involved a complex series of tests using ferrets. The researchers first found the gene for the receptor and looked to see whether the gene was "turned on" and creating the required proteins.

Molecular analysis demonstrated that the receptor was present on the ferrets' brainstem neurons. Other techniques allowed the researchers to see the consequences of activating the receptor, proving it works.

Keith A. Sharkey, the study's lead author, believes that the receptors will work the same way in humans as they do in ferrets.

He emphasizes, however, that this does not prove that smoking marijuana is a good treatment for nausea.

Drugs that originate outside the body, such as cannabinoids from smoked marijuana, "may not act at these receptors," said Sharkey, a professor of physiology and biophysics at the University of Calgary in Canada.

"Our work shows that it is the endogenous cannabinoids—the body's own chemicals—that can be targeted to these receptors."

Using the cannabinoids as a basis for therapeutic drugs is not a new idea. But Sharkey says that the recent findings demonstrate that cannabinoid drugs can be developed to target a specific region of the brain without unwanted side effects.

What does this mean for future cannabis-based drug development?

"I have every reason to imagine—and some insights—that the global pharmaceutical industry is busy working on these types of molecules to make potential therapeutics," he said.

"Our data would be supportive of these approaches for the treatment of any disorders that involve cannabinoid actions in the brain, and elsewhere too."

Making New Neurons

The receptor discovery is not the only good news for proponents of medical cannabinoids. The chemicals may relieve depression and anxiety and improve memory as well.

A study published online today by the Journal of Clinical Investigation reports that a synthetic cannabinoid promotes the growth of new neurons in a region of the brain called the hippocampus, which is associated with memory.

The finding that production of new neurons, or neurogenesis, can occur at all in the hippocampus is itself a relatively new discovery.

In rats the effect of cannabinoid is dramatic: Chronic high doses of the substance relieve anxiety and depression, a result attributable to the birth of new neurons.

Xia Zhang, an associate professor of psychiatry at the University of Saskatchewan and senior author on the paper, notes that the synthetic cannabinoid is about a hundred times as potent as the street drug tetrahydrocannibinol, or THC.

Still, he says, "these results indicate that smoking marijuana may also produce more neurons in the hippocampus" with similar beneficial results.

The synthetic chemical specifically targets cannabinoid receptors, while THC, the cannabinoid in smoked marijuana, targets other receptors as well.

The study did not specifically examine the issue of whether an increase in neurons would result in cognitive improvements. But according to Zhang, "more newborn neurons in the hippocampus would improve hippocampal-dependent learning and memory."

The finding raises an obvious question: Why is it that marijuana use, far from improving memory, is known for having the opposite effect?

"This is a question I've answered many times," Zhang said. "The acute use of marijuana or cannabinoids would definitely temporarily impair memory in both humans and animals.

"However, it is possible that chronic use of marijuana may improve memory once the newborn neurons in the hippocampus become mature, one or two months after they are born. We expect to do this experiment in the near future."

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