Pot without the high

It's a stoner's worst nightmare: pot without the high. But a drug that offers the pain-killing and appetite boost associated with marijuana without the forgetfulness, giggles and general dopiness might appeal to cancer patients and others who would otherwise turn to medical marijuana.

The approach hinges on tinkering with our body's own natural stash of marijuana-like chemicals, endocannabinoids. Marijuana's active ingredient delta-9-tetrahydrocannabinol (THC) tickles the same brain cell receptors as two endocannabinoids: one that makes you high (2-AG), while another that kills the pain (andamide).
A team led by John Casida, a toxicologist at the University of California in Berkeley, discovered that a pesticide related to the nerve gas sarin causes some of the same effects as marijuana in mice, including the painkilling and the behavioural changes.

But the drug works nothing like pot. Instead of turning on the brain's THC receptors, the insecticide gets mice high by blocking their brains from breaking down both 2-AG and andamide.

The next step will be to find a drug that stymies the breakdown of andamide, not 2-AG. But scientist will need to be careful before they mellow this high. "If your start with something derived form a pesticide you have to be particularly careful," says Casida.