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Friday, November 7, 2008

Research into medicinal marijuana grows up.

Marijuana. Click image to expand.


This summer, British and Italian researchers found that in a laboratory plate, molecules in marijuana can slay the superbug methicillin-resistant staphylococcus aureus, which recently infected seven babies and four employees in a Yonkers, N.Y., maternity ward, heightening fears of outbreaks in schools and locker rooms, as well as in its more familiar breeding grounds, hospitals and nursing homes. In theory, compounds derived from the cannabis plant could someday serve in topical creams for patients with MRSA or other antibiotic-resistant infections.

This isn't the first time marijuana has tantalized the world as a possible wonder drug. In recent years, compounds in cannabis or related molecules have been shown to slow the growth of lung tumors in mice, decrease hardening of the arteries in rats, and boost the egg-binding capability of tobacco smokers' sperm. Research on the receptors that THC and other cannabis compounds attach to—and the nitty-gritty mechanisms by which they exert their effects—has been booming. So has work on native molecules, called endocannabinoids, that bind to the same sites. These molecular interactions affect a wide range of functions, from appetite to inflammation to the perception of pain.

The onslaught of basic science has helped to separate cannabis from an association with hippies and recreational pot smokers. It has also spurred hopes that these molecules (or similar ones) might prove therapeutic for traumatic brain injury, inflammatory bowel disease, allergic contact dermatitis, atherosclerosis, osteoporosis, and Alzheimer's disease, among others. For all the razzle-dazzle, though, potential treatments frequently seem stuck in perpetual adolescence. Research on traumatic brain injury seemed promising but got mixed results in human clinical trials, while most of the others simply haven't gotten very far in the experimental process.

Still, a few prospects show signs of inching toward adulthood. The most enticing are aimed at lessening pain associated with nerve damage and improving some symptoms of multiple sclerosis. Between 2007 and this summer, several randomized clinical trials have found that smoking marijuana can relieve pain in patients with nerve degeneration caused by HIV or other disorders. Compounds in cannabis also seem to reduce nerve pain and possibly decrease spastic movements in people with MS. A drug called Sativex—which delivers two cannabis compounds in a spray under the tongue—is now in late-stage clinical trials in Europe for MS patients. Much as we've heard the hype before, these findings deserve some notice even from the jaded.

Studying the upside of marijuana can be a bureaucratic nightmare. In 1970, Congress deemed it a Schedule 1 drug, meaning that it has a high potential for abuse and "no currently accepted medical use"—making research on possible benefits a tough sell. In the 1980s, the Food and Drug Administration approved Marinol, an oral formulation of THC, the most psychoactive ingredient in cannabis, to treat nausea and vomiting associated with chemotherapy. Later, it also approved Marinol to boost the appetites of people with AIDS. But Marinol was never fully accepted by patients, says Donald Abrams, a professor of clinical medicine at the University of California-San Francisco. It took effect more slowly than smoked marijuana and was also more psychoactive. (When THC enters the bloodstream from the digestive tract, it is broken down by the liver into even more psychoactive molecules.) Nor has Marinol been approved in the United States to treat pain. Those who wished to push research further—whether by studying smoked marijuana, developing better formulations, or testing cannabis for other conditions—got no love from the federal government.

Some did get a boost, however, from the state of California, which paid for the recent work on cannabis smoking and pain. In 2000, the state funded the University of California's Center for Medicinal Cannabis Research, which vets research proposals with an NIH-style review process, pays for projects, and helps scientists navigate state and federal regulations. The center helps researchers obtain cannabis cigarettes, for instance, and deal with federal rules for record-keeping and security—like making sure the safe in which the drug is stored is properly bolted to the floor, says director Igor Grant.

The work has moved slowly, but it's finally paying off with a handful of publications. The first clinical-trial-based paper, which appeared in Neurology in 2007, was a randomized study of 50 patients with HIV-related nerve damage, which can cause discomfort often described as aching, painful numbness, or burning. Those who smoked cannabis each day reported a 34 percent decrease in chronic pain—an effect that's on par with medications often used for this condition, like anti-convulsants and antidepressants, says Abrams. Two other randomized clinical trials, published in June and August, found similarly clear benefits. The June study focused on patients with pain related to a range of neurological conditions, including spinal cord injury. The August paper focused again on HIV-related symptoms. Both found that patients who smoked cannabis reported significantly less pain than those who used dummy cigarettes. These studies were relatively small, but cumulatively they are persuasive.

Other recent research suggests that cannabis can relieve MS-related pain and may be able to help other symptoms, too. Sativex, which contains THC and cannabidiol, a nonpsychoactive compound, and is absorbed through the mouth, is already approved in Canada for cancer-related pain and nerve pain associated with MS. In 2007, this randomized clinical trial of 189 MS patients found that those who took Sativex self-reported a significant decrease in involuntary muscle spasms. (The study was funded by GW Pharmaceuticals, the British company that developed the drug.) Researchers are now conducting a late-stage clinical trial of Sativex in MS patients across five European countries. The company has also begun a Phase II/III clinical trial in the United States for patients with cancer-related pain. Sativex may offer particular advantages because it is neither smoked nor swallowed: It does not introduce toxins to the lungs, as smoking does. It enters the bloodstream rapidly but does not pass initially to the liver, as oral formulations do, which prevents it from getting broken down as quickly and may make it less psychoactive. (GW Pharmaceuticals says that patients who take Sativex tend not to experience psychoactive side effects at normal dosage levels.)

If these serious investigations and results continue, soon cannabis therapies may not, in fact, be bolted to the floor.