High anxiety?

The human brain produces compounds called endocannabinoids that act on these receptors, and are involved in anxiety and fear-learning, or the learning of which threats to be afraid of. But little has been known about the effect of THC, an exogenous cannabinoid, on the brain’s own system.

For ethical reasons, the researchers did not give THC to non-marijuana users, and the study was small. But the findings in the study volunteers suggest that THC and other compounds that act on the CB1 receptors in the amygdala could be fruitful targets for new anti-anxiety medicines. Phan notes that rimonabant, a smoking-cessation and weight-loss drug not yet available in the United States for clinical use, also acts on the CB1 receptor.

Understanding how drugs such as marijuana affect the brain may also help reveal more about why people become addicted to illicit drugs or abuse certain prescription drugs, Phan notes. Some individuals may be using illicit drugs and misusing prescribed drugs to alleviate their anxiety. He hopes to investigate this issue further by studying people who have used prescription pain drugs recreationally (such as oxycodone), using new funding from the National Institutes of Health.

The THC study links three key domains of human behavior: a specific region of the brain, the function of that area, and a neurochemical agent (THC) that appears to act on them. The new sertraline study will take it one step further, by looking at genetics too. Specifically, Phan and his colleagues will look for variations (“functional polymorphisms”) among several genes in individual subjects. Key among them is the gene (5-HTTLPR) that encodes the serotonin transporter protein that transports the neurotransmitter serotonin in and out of brain cells. Serotonin has long been known to be involved in depression and anxiety, and indeed most modern antidepressant and anti-anxiety drugs (such as SSRIs) work on this transporter.

Reference: Journal of Neuroscience, March 5, 2008, Vol. 28, No. 10, 2313-2319

More information about the new study is available on the U-M Engage web site, www.umengage.org, or via 734-232-0199 or .