Increasing levels of kynurenic acid, a naturally occurring compound in the brain, reduces the rewarding properties of the main psychoactive ingredient in marijuana in rats and monkeys, reports a paper published this week in the journal Nature Neuroscience. The study finds that kynurenic acid also prevents relapse in animal models of cannabis abuse.
Like all drugs of abuse, the main psychoactive ingredient in marijuana, Δ9-THC, increases activity in the dopamine reward system in the brain. Blocking alpha 7 nicotinic acetylcholine receptors (α7nAChRs), can prevent the increased dopamine neuron activity caused by THC and could be helpful for drug abuse treatment. However, drugs that block these receptors can produce undesirable side effects. In contrast, increasing levels of natural modulators of these receptors could be a safer and more effective approach.
Robert Schwarcz and colleagues show that pharmacologically enhancing levels of kynurenic acid, which naturally blocks α7nAChRs, with the drug Ro 61-8048 prevents monkeys and rats from taking cannabinoids. Moreover, in animals with a history of repeated cannabinoid intake, Ro 61-8048 prevented relapse after either a small dose of Δ9-THC or presentation of a cue previously associated with taking the drug. Though further studies need to be conducted on the effect of raising kynurenic acid levels in humans, these results suggest that modulating kynurenic acid levels in the brain may be an effective approach to treatment of marijuana dependence in humans.