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Biological Chemistry

Potential Treatment For Marijuana Abuse

When administered to monkeys, small molecule dials down the desire for marijuana’s active ingredient

by Lauren K. Wolf
October 21, 2013 | APPEARED IN VOLUME 91, ISSUE 42

About 9% of the 17.4 million people in the U.S. who smoke marijuana become dependent on the drug, according to the National Institute on Drug Abuse (NIDA). Looking for treatment options, a research team led by Robert Schwarcz of the University of Maryland School of Medicine and Steven R. Goldberg of NIDA tested the effects of a compound called Ro 61-8048 on squirrel monkeys conditioned to repeatedly dose themselves with Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana (Nat. Neurosci. 2013, DOI: 10.1038/nn.3540). When injected into these animals, Ro 61-8048 boosted the amount of kynurenic acid produced by their brains, the team found. This neurochemical, the researchers believe, deactivates α7-nicotinic acetylcholine receptors on neurons in one of the reward centers of the brain by changing the receptors’ conformation. Deactivation of the receptors disrupts nerve cell signaling that eventually results in the pleasurable release of dopamine. Monkeys given Ro 61-8048 pressed a lever to receive a THC injection significantly fewer times than animals not given Ro 61-8048. The doses of Ro 61-8048 tested were effective in blocking THC’s addiction-related effects without causing cognitive side effects, Schwarcz says, “so this bodes well for clinical use.”

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