By Kai Kupferschmidt
Medical marijuana can alleviate pain and nausea, but it can also cause decreased attention span and memory loss. A new study in mice finds that taking an over-the-counter pain medication like ibuprofen may help curb these side effects.
"This is what we call a seminal paper," says Giovanni Marsicano, a neuroscientist at the University of Bordeaux in France who was not involved in the work. If the results hold true in humans, they "could broaden the medical use of marijuana," he says. "Many people in clinical trials are dropping out from treatments, because they say, 'I cannot work anymore. I am stoned all the time.' "
People have used marijuana for hundreds of years to treat conditions such as chronic pain, multiple sclerosis and epilepsy. Studies in mice have shown that it can reduce some of the neural damage seen in Alzheimer's disease. The main psychoactive ingredient, tetrahydrocannabinol (THC), is approved by the Food and Drug Administration to treat anorexia in AIDS patients and the nausea triggered by chemotherapy. Although recreational drug users usually smoke marijuana, patients prescribed THC take it as capsules. Many people find the side effects hard to bear, however.
The exact cause of these side effects is unclear. In the brain, THC binds to receptors called CB1 and CB2, which are involved in neural development as well as pain perception and appetite. The receptors are normally activated by similar compounds, called endocannabinoids, that are produced by the human body. When one of these compounds binds to CB1, it suppresses the activity of an enzyme called cyclooxygenase-2 (COX-2). The enzyme has many functions. For instance, painkillers such as ibuprofen and aspirin work by blocking COX-2. Researchers have hypothesized that the suppression of COX-2 could be the cause of THC's side effects, such as memory problems.
But that's not what researchers found in the new study. A team led by Chu Chen, a neuroscientist at Louisiana State University, discovered that giving THC to mice increased the activity of COX-2. Blocking this activation alleviated the memory and learning problems triggered by THC. For instance, mice that received a dose of THC daily for a week had problems remembering the location of a hidden platform in a water tank. If COX-2 was blocked, however, mice given THC found the platform just as fast as mice that were not treated with THC did. This result suggests "that the unwanted side effects of cannabis could be eliminated or reduced . . . by administering a COX-2 inhibitor," the authors wrote last month in Cell.
Raul Gonzalez, a psychologist at Florida International University, praises the "elegant set of experiments." But he warns that it is not clear whether inhibiting COX-2 blocks the beneficial effects of marijuana. In the study, Chen and colleagues showed that some positive impacts of THC, such as those observed in mouse models of Alzheimer's disease, are still seen if the mice also receive a COX-2 inhibitor. But such an inhibitor may still interfere with the positive effects of THC on other disorders such as AIDS, Gonzalez writes in an email. "It is much too early to tell, but the current study will undoubtedly spur some exciting new research."
One conclusion of the paper is that THC and endocannabinoids can cause opposite effects when they bind to CB1, Marsicano says. That suggests that it may be too simple to think of a receptor like CB1 as a mere switch that always does the same thing if it is activated, he says. For instance, CB1 may come in slightly different forms, and THC may be particularly good at binding to only one of these forms.
The authors argue that a painkiller like aspirin may also prevent some of the downsides of cannabis abuse. But Gonzalez cautions that smoked cannabis contains many more active compounds than THC does, and they may also be involved in harming the memory and other side effects.
As for people who use marijuana recreationally, taking ibuprofen as well might kill the buzz they're looking for, Marsicano says. For instance, he says, impairments in working memory may make people prone to jump from one topic to the next during conversation, and they may have fun doing that. "So what we call side effects may attract people to marijuana in the first place."