Scientifically Speaking, This Drug's on the Wrong List

Take, for example, the question of addiction. Research indicates that when THC stimulates cannabinoid receptors in the brain, it engages a complex circuit of neural cells and transmitters that are normally involved in the response to rewarding stimuli, such as tasty foods. A brief burst of activity in this circuit produces only a pleasant sensation, but if the stimulus persists for a long time (as it does with frequent and heavy marijuana use) it can eventually cause changes in the neural circuit that result in tolerance -- the need to take larger amounts of drug to produce the same effect -- and dependence -- the feelings of unease and craving experienced when prolonged drug use is suddenly stopped.

Heroin's interaction with its opiate receptors triggers a much more intense sensation of pleasure than does marijuana -- so intense, indeed, that heroin addicts are at a loss to put it into words. But heroin's withdrawal is far more severe emotionally than marijuana's, and unlike the latter, it causes a myriad of physical symptoms including shivering and pain. It's not a higher degree of the same response -- it's a different response to a different chemical reaction.

All potential benefits of marijuana, such as its ability to increase appetite and ease nausea, are also caused by the binding of THC to its brain receptors. This is one of the main sources of trouble with developing medicinal uses for marijuana: If a single receptor is responsible for all actions of the drug, how can we tease apart the good from the bad? One way to do this may be to forgo smoked marijuana and find better methods to deliver THC -- for example, metered aerosols such as those used in asthma -- which would allow patients to take just enough drug to control their symptoms, minimizing unwanted side effects. This strategy would also avoid inhaling the dangerous mixture of toxic and cancer-promoting chemicals present in marijuana smoke.

Another way to offset marijuana's risks may be to take advantage of the fact that cannabinoid receptors did not evolve in the human brain to give us the opportunity to experience a high. Rather, their original role is to combine with a set of THC-like chemicals produced by brain cells, whose functions include the control of pain and anxiety. If we could design chemicals that tweak the levels of these transmitter substances in the brain, we might be able to boost their normal effects. Our lab and others throughout the world are now working in this direction with the goal of creating new classes of painkiller, anti-anxiety and antidepressant drugs.

Because of THC's Schedule I status, that research sometimes faces extra bureaucratic hurdles. But preventing a few months of paperwork to a scientific project is not the main reason the drug and its derivatives should be reclassified to a schedule that is in accord with their medical utility. Far more important is the goal of having realistic drug laws in this country that penalize drug abuse but also encourage medical progress.

Ever since the enactment of the CSA, advocates have been pressing for THC to be reclassified. These pleas have gone unheeded so far. Perhaps the Supreme Court decision will inspire citizens and medical organizations to take a fresh look at the scientific evid

ence without being blinded by prejudice. This evidence suggests that, while marijuana is an addictive drug that requires careful monitoring, its active constituents can be useful in medicine when appropriately employed. But it's hard to get this message across: All too often, the voice of science and reason is lost in a polarized shouting match.

Daniele Piomelli is professor of pharmacology and director of the Center for Drug Discovery at the University of California, Irvine.