Search is on for new anti-addiction drug targets

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A new generation of researchers is actively pursuing novel drug targets for an as-yet elusive pill to turn off addictions to food or cocaine, Discover Magazine reports.

Their goal: To reduce levels of dopamine in the body in order to reduce cravings. High levels of dopamine enhance pleasure, and those levels increase, for example, with drugs like cocaine. Researchers hope to reduce dopamine levels by hitting parts of the endocannabinoid system series of receptors and proteins in the nervous system, brain, stomach and elsewhere, which regulate cravings and mood, among other things.

The thing is, as Discover reminds us, Sanofi-Aventis ($SNY) did this before with rimonabant, a drug that targeted the C1 receptor in the endocannabinoid system and appeared to reduce cravings, but made many folks suicidal. To say this is bad is an understatement, and Discover notes that the FDA rejected the drug. The company pulled it from the European market in 2008 due to safety concerns, two years after its commercial launch.

Zheng-Xiong Xi at the National Institute on Drug Abuse in Baltimore has found two possible new approaches. He tested THC, the active compound in marijuana, and JWH-133, both of which appeared to latch onto CB2 receptors in mice and reduce dopamine levels without depressing the animals. And they craved a lot less cocaine.

Another group of scientists from the University of Calgary and Northeastern University have developed a compound called AM6545 that targeted CB1 in the stomach but not in the brain, according to the Discover article. Mice who were tested with the drug reduced their eating and lost weight without getting visibly nauseous or depressed.

The Discover piece notes that the endocannabinoid system offers a wide swath of potential targets because its receptors and proteins are in so many places in the body. While results in humans can be very different than in mice, the researchers said they will continue their efforts.

- here's the Discover Magazine story

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