Is Big Pharma Trying to Take All the Fun out of Pot?

Pricey pharmaceutical-marketing newsletters have touted cannabis-derived drugs as the next blockbuster for the industry, but the biggest companies are primarily researching drugs whose effect is the opposite of the cannabis herb.

Numerous drug researchers are trying to develop medications that replicate the herb's therapeutic effects without the harm of inhaling smoke and the side effect of getting people high.

Others are looking into cannabinoid agonists, drugs that enhance the body's natural cannabinoid system -- or cannabinoid antagonists, which disrupt it, and have been the pharmaceutical industry's main focus. Despite the millions of medical-marijuana users, both U.S. government restrictions and drug companies' need for exclusive ownership have limited research into herbal cannabis.

In any case, it will likely be a while before many cannabis-derived drugs arrive in your local pharmacy.

"There's a lot of interest out there, but there's nothing that's going to be released in the next week," said a longtime medical-cannabis researcher who asked to remain anonymous.

So far, only three such drugs are on the market.

• Cesamet (Valeant Pharmaceuticals), used for chemotherapy-nausea treatment, went on sale in the United States in 2006. It contains nabilone, a synthetic analog of THC, the primary psychoactive ingredient in cannabis.
• Marinol, synthetic THC in capsules, has been on the market since 1986. It is now manufactured by the Belgian firm Solvay Pharmaceuticals, and generic versions are beginning to come out.
• Sativex, a whole-cannabis-extract spray produced by the British firm GW Pharmaceuticals, is available in Canada. It is oromucosal, meaning it is absorbed by the mucous membranes under the tongue and on the inside of the cheeks, and it contains approximately equal proportions of THC and cannabidiol (CBD). CBD is a cannabinoid thought to reduce both pain and the more nerve-jangling aspects of the marijuana high. The spray is undergoing Phase III trials -- large-scale human studies of its efficacy -- for multiple sclerosis in Europe and cancer pain in the U.S.

At least five of the world's top 10 pharmaceutical companies have looked into the field. In 2006, there were about 18 cannabinoid-related compounds under active pharmaceutical development, says Dr. George Kunos, scientific director of the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health. They were primarily cannabinoid antagonists.

Many of those, however, may never make it to market. New drugs need to be proven safe and effective, drug companies want them to be profitable, and the approval process can take as long as 10 years.

In January, Novartis announced that it had completed Phase I tests of a cannabinoid agonist called CRA13, which might be used to treat chronic pain. Phase I tests are a small-scale study of the drug's safety, how well human subjects tolerate it, and its "pharmacokinetics" -- how quickly it gets into the body, where it goes and how long it stays.

Big Pharma's first move into cannabinoid drugs, however, ended in failure. In 2006, the French company Sanofi-Aventis began selling in Europe rimonabant, a cannabinoid antagonist, as an appetite suppressant under the brand name Acomplia.

By blocking the action of natural cannabinoids at "CB1 receptor" sites in the brain, Acomplia created the opposite of the "munchies." (As one drug company put it, activation of CB1 receptors "appears to provoke food intake even in the setting of satiety.") The drug also showed promise for diabetes, says Kunos, because it increased the body's sensitivity to insulin. A British pharmaceutical-business newsletter predicted that Acomplia would be "the first of the cannabinoid blockbusters."