May 1, 2014

Related NIDA Notes Article

Dr. Joni Rutter Q&A: How Basic Science Is Tackling Addiction


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Length: 04.20 minutes | Download the MP3 (2.73 MB)



There’s a long-standing observation that not everyone who tries or takes drugs becomes addicted.

So there are individuals who are more vulnerable to addiction, and there are individuals who are more resilient to addiction, once they take that drug.

And our goal is to try to understand, what are the individual differences that contribute to whether or not someone becomes addicted or doesn’t become addicted.

With genetics, there’s been a key finding, I would say, in that—specifically in the area of smoking and nicotine dependence.

There was a study done a few years back where they took individuals who were heavy smokers and they compared them to individuals who were not heavy smokers—they tried smoking in their lifetime, but never became addicted, never smoked a lot of cigarettes.

And what they did is they looked at the genomes of those two groups and they compared the genetic variation between those two groups.

And they found a specific genetic factor in the nicotinic subunit receptor called alpha 5.

And within this alpha 5 nicotinic receptor, there’s one single base pair difference, and it’s not infrequent in individuals—it’s probably about 20 to 30 percent across all the individuals.

But if you have this risk allele for this genetic variation, it turns out that you are more prone to heavy smoking.

This alpha 5 risk gene—alpha 5 risk allele—is in a sense acting as a gate in a particular region of our brain called the habenula.

And the habenula—in this situation, in smokers, the habenula acts as sort of a gate—it’s more for the aversive effects of smoking.

So it’s not the rewarding effects, it’s the aversive effects.

In individuals with this particular risk allele in the gene for alpha 5, they are unable to close their gate, if you will, so they don’t have that aversive feeling or that aversive outcome when they smoke cigarettes.

And so they continue to intake or consume cigarettes much more frequently than do the individuals who don’t have this risk gene for the alpha 5.

Given that we do have this information about the particular genetic—or alpha 5 gene and that genetic variation within the alpha 5 gene, that combined with other information that we have on the genetics of how nicotine is metabolized, we can combine that information and we can actually predict—or we hope to predict—whether someone will be more responsive to a particular nicotine replacement therapy, like the gum or the patch, versus a newer medication, something like varenicline or Chantix.

We don’t have the information just yet, but we hope that this information will give us the ability to inform physicians on perhaps how to treat those individuals that come into their office with these specific genetic variations and match them to a particular treatment that is appropriate for those genetic variations.