The Epigenetic Factor in Addiction


Substance use disorders are complicated. The disease of addiction is “chronic, subject to relapse, and influenced by genetic, developmental, behavioral, social, and environmental factors,” wrote the Surgeon General in his comprehensive report in 2016.  

Addiction is influenced by many factors and research has repeatedly shown that some people get more easily addicted than others when using the same substances. The difference is typically a genetic predisposition and stress. In Hooked, a short guide to the mechanics of addiction, Arwen Podesta, M.D., offers the simple formula: Biology (genetics and epigenetics) + Stress (especially trauma) + Drug = Risk of Addiction.

According to the National Council on Alcoholism and Drug Dependence (NCADD), “genetics make up 50 percent of the risk for alcohol and drug dependence.” That’s a pretty significant risk factor and it has become increasingly clear that human DNA is not as static as once thought.

Which brings us to epigenetics, the study of how genes are switched on or off. Epi is a Greek prefix meaning “above” and epigeneticists study “functional, and sometimes inherited, changes in the regulation of gene activity and expression that are not dependent on gene sequence,” according the National Institute on Drug Abuse (NIDA).

In other words, your environment and behavior can cause changes in your genetic makeup. Some experts believe that “70 percent of your health-related genes can be expressed differently by different intake and lifestyle,” writes Dr. Podesta. This makes the second risk factor, stress, even more important. If there is intense and prolonged stress or even trauma, certain genes can be switched on and these changes can even be passed on to children and grandchildren.

Recent research at the University of Cambridge in England indicates that more DNA modifications than previously thought may exist in humans and other vertebrates. And these changes can even be engineered.

Scientists at the University of British Columbia in Vancouver, Canada recently were able to genetically engineer a mouse that does not become addicted to cocaine.

“Through genetic engineering, we hard-wired in place the synapses in the reward circuits of these mice,” explains co-lead author Andrea Globa. “By preventing the synapses from strengthening, we prevented the mutant mice from ‘learning’ the memory of cocaine, and thus prevented them from becoming addicted.”

"Addiction is a form of learning," UBC neurologist Shernaz Bamji told NPR. “Somehow, these mice never learned to associate the pleasurable feelings produced by cocaine with the place where they received the drug.”

The mice the researcher created had higher levels of a protein called cadherin but as the UBC team points out, “finding a way of augmenting cadherin as a way of resisting addiction in humans is fraught with pitfalls.” That means, there won’t be a “cocaine immunization” anytime soon.

But the finding emphasizes once more that people with a certain genetic predisposition are especially susceptible to addiction. "Addiction is not just bad judgment, but really has more to do with our biology and our biochemistry," says Bamji.