Drug That Blocks Stress Receptor May Curb Alcohol Craving

Anxiety, drugs, and the brain’s “fear center.”

A brain receptor for a neurotransmitter involved in stress and anxiety has become a primary target in the scientific war on alcoholism—the only kind of drug war that really matters.

Researchers at the National Institute of Alcohol Abuse and Alcoholism (NIAAA), working with colleagues at Lilly Research Laboratories and University College in London, announced that a drug that blocks the so-called NK1 receptor (NK1R) reduced alcohol cravings in a study of 25 detoxified alcoholic inpatients. The drug “suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses.”

The study, published in the current issue of Science magazine, (look here for abstract) demonstrates that investigators continue to work toward more effective anti-craving drugs from a variety of angles. The NIAAA researchers are making effective use of recent findings about the role played by corticotropin-releasing hormone (CRH) in the addictive process. CRH is crucial to the neural signaling pathway in areas of the brain involved in both drug reward and stress.

Another neurotransmitter of this type is substance P, together with its preferred receptor, NK1R. As it happens, NK1R sites are densely concentrated in limbic structures of the mid-brain, such as the amygdala, or so-called “fear center.” The experimental drug, known as LY686017, blocks NK1R receptors, shutting off substance P, which in turn diminishes anxiety-related drug cravings.

Other researchers had previously demonstrated that deletion of NK1R sites eliminated opiate use in animal models. It has also been known for some time that alcohol and the opiates share certain common chemical pathways in the brain. And in humans, at least one earlier study showed decreased stress and anxiety reactions in human subjects taking a drug that blocked the Neurokinin 1 receptors.

The authors of the study suggest that “blockade of NK1Rs might modulate stress- and reward-related processes of importance for excessive alcohol use and relapse.”

According to NIAAA director Dr. Ting-Kai Li, “These findings advance our understanding of the link between stress and alcohol dependence and raise the prospect of a new class of medications for treating alcoholism.”

The early finding will require more research. “To our knowledge,” the authors conclude, “no data are presently available to address this hypothesis.”

graphic credit: http://www.ibiblio.org/rcip/ptsdmemory.html