HMN 2025: How New treatment with designer proteins could disrupt cycle of addiction without stifling natural pleasure

A new biochemical approach to combat addiction, developed by researchers at the University of California San Diego and the National Institute on Drug Abuse (NIDA), has shown promising results in reducing drug-seeking behavior.

By custom engineering proteins in the brain, called ion channels, to be activated by cocaine, the new approach is able to reverse the rewarding effect of cocaine, but only when cocaine is actually present in the body. This effectively breaks the positive feedback loop of addiction.

While addiction is driven by positive feedback loops in the brain, these same neural responses are also involved in the enjoyment of natural rewards, such as food or exercise. One goal of addiction research is to find ways to reverse this cycle of addiction without affecting the enjoyment of natural rewards.

Using a rat model, the researchers found:

• Rats expressing the cocaine-activated ion channels in the lateral habenula (LHb), a brain region involved in regulating reward and motivation, showed a significant decrease in cocaine-seeking behavior.
• The cocaine-activated ion channels caused LHb neurons to become excited only when cocaine was present. This decreased the dopamine boost normally caused by cocaine, leading to less frequent cocaine consumption.
• The expression of these engineered ion channels did not affect food-seeking or other natural behaviors in the absence of cocaine.

This approach could potentially lead to the development of gene therapies for cocaine addiction that do not impact the enjoyment of regular activities, which would provide a new treatment option for individuals struggling with addiction. The researchers also hypothesize that this approach could be extended to other addictive substances, as the underlying neurobiology of addiction is similar across different substances. However, this potential, as well as advancing the approach into human trials, will require further research to demonstrate.

The study, published in Nature, was led by Scott Sternson, Ph.D., in the Department of Neurosciences at UC San Diego School of Medicine and Michael Michaelides at NIDA. Sternson is an inventor on a pending patent application for this technology.