Marijuana's Active Ingredient Targets Deadly Brain Cancer

From the WebMD Archives

Feb. 28, 2000 (Atlanta) -- If results of a recent rat study hold true in human trials, marijuana could be the treatment of choice for patients with malignant glioma -- an especially aggressive and often fatal form of brain cancer. No, rats haven't started smoking pot. But when researchers injected tumorous animals with cannabinoids -- the drug's active ingredient -- about a third of them went into remission, and another third lived significantly longer than untreated rats. The findings appear in the March issue of the journal Nature Medicine.

The study does not mean that smoking pot will cure cancer in humans, says Daniele Piomelli, PhD, author of an editorial accompanying the paper. "What it does show is that in about one-third of animals injected with a potent cannabis mimic, the cancer disappears and in another one third, it is reduced. Given the seriousness of malignant glioma, it's a very important observation that deserves to be followed up," he tells WebMD. Piomelli is professor of pharmacology at the University of California in Irvine.

According to lead researcher Manuel Guzmán, PhD, his team's previous studies showed that cannabinoids could stop growth and kill cancer cells but did not harm normal cells. The current work examined the action behind this effect and whether it would also work in living animals. Guzmán is a biochemistry lecturer at Complutense University, Madrid.

The researchers first caused tumors in the brains of 18 rats. They then injected the animals over the course of seven days with either a natural or artificial cannabinoid, or a placebo for comparison. Additional groups of healthy, tumor-free rats also received the various treatments.

All of the untreated animals with tumors died between days 12 and 18, but those treated with the cannabinoids lived much longer, and had significantly smaller tumors. Approximately one-third of treated animals showed no response at all to the cannabinoids, indicating that the treatment might not work for all patients. There were no negative side effects at all in the healthy animals receiving treatment.

According to Guzmán, in the body there are two kinds of cannabinoid receptors, or parts of a cell that the cannabinoid connects with like a key fits into a lock. Once connected, the receptor is activated or "turned on." In the brain these receptors are called CB1, and in the rest of the body they are called CB2. In another set of experiments, the researchers tested exactly which of these receptors had to be activated in order to cause cancer cell death. They found that the cannabinoid was activating both receptors. Guzmán says activating either of the receptors is enough to induce cell death, while blocking both completely eliminates the effect.

It is only CB1 activation that induces marijuana's euphoric or "high" effects, says Guzmán, so if we could "specifically activate only CB2 receptors, we could kill the cancer cells without producing any kind of psychotropic effect." Unfortunately, however, the cannabinoids that would only activate the CB2 receptor are not yet available for experimentation.

Both Guzmán and Piomelli express concern that ethical debate over medical marijuana use will hinder future investigation.

"It is stupid," says Guzmán, "because if these compounds were present in pine leaves or lettuce, then most likely things would be different. But they are present in marijuana, so it's controversial ... which is nonsense. Hospitalized patients are given morphine and other drugs, but for some reason, it's considered immoral to give them cannabis."

In Piomelli's opinion, placing restrictions on clinical use and testing of marijuana-based therapies is "not only silly, it can be criminal. When patients are dying, there should be no consideration to such matters," he tells WebMD.

Malignant glioma is "fairly common and very deadly," Piomelli says. "I believe it would be ethically acceptable to offer [cannabinoids] to patients, especially in light of the fact that the toxicity is likely to be very, very small."