Marijuana's brain receptors mapped.

Marijuana's brain receptors mapped

A pharmaceutical company's futile attempt to make a medically acceptable marijuana molecule has helped researchers understand how the drug gives its "high."

Scientists at the Groton, Conn.-based Pfizer Central Research finally gave up their attempts to make a nonpsychoactive analog of marijuana's primary active ingredient--delta-9 tetrahydrocannabinol (THC)--which they believed had great potential as a painkiller. But Miles Herkenham of the National Institute of Mental Health in Bethesda, Md., and his colleagues used one of the company's especially potent versions of THC to map, for the first time, the location of THC receptors in the brain.

Normal THC is so chemically "greasy" it sticks to and contaminates laboratory glassware and doesn't lend itself to being radioactively labeled. The Pfizer analog had a classic THC-receptor binding site but was more amenable to radio-labeling experiments, allowing the researchers to see where it went in rat and marmoset brains.

"It's gratifying to see the distribution," Herkenham says, since it matches so well the drug's pharmacology. Most of the receptors are in the hippocampus -- where scientists think memory consolidation may occur, and where the external world may get translated into a spatial and cognitive "map." They also found receptors throughout the cortex, the site of higher cognition. The distribution might explain marijuana's reported detrimental effects on memory -- and its more popular effects on mental activity and spatial orientation.

Herkenham found very few receptors in the brainstem, where critical life-support controls are based. This might explain why it's almost impossible to die from even extremely high doses of the drug, he says. Some receptors in the spinal cord might explain pot's analgesic effects--which in this analog are more powerful than morphine, Herkenham adds.

Unfortunately, as Pfizer learned and Herkenham's animals confirmed, the psychoactive properties of pot are inseparable from the painkilling parts. His test animals "were incredibly high," he says. How could he tell? "It was obvious."