Are some people more predisposed to opioid addiction than others? It’s a good question, an important question, and we’ve addressed it here before at AddictionNews. In a recent post, we quoted research that indicates that 50% of opioid dependency is based on genetics.

The number 50% seems oddly round and highly suspect. It’s also remarkably unscientific, because it is based on assessing whether someone diagnosed with substance use disorder has a family history of substance use disorder. Roughly half do, but family history and genetic certainty are two different kinds of evidence.

Enter the Marshall University Joan C. Edwards School of Medicine in West Virginia, where researchers just landed a $3.3 million grant from the National Institute on Drug Abuse for a five-year study into the genetics of fentanyl addiction. The research is being led by associate professor, Price E. Dickson, Ph.D., and involves the study of “genetically diverse” mice with the goal:

[T]o discover the genes and brain mechanisms that underlie vulnerability and resistance to fentanyl addiction.

Research into the genetics of opioid addiction is remarkably thin, according to an article in the journal, Pharmacogenetics and Genomics, which laments, “Surprisingly, little is known about the pharmacogenetic influences on fentanyl pharmacokinetics or pharmacodynamics.” Giving weight to the newly-announced Marshall University grant, the review concludes:

DNA sequencing may be needed to determine whether pharmacogenetic differences may contribute to lethal opioid overdoses.

One of the few studies involving humans comes from the world of cancer recovery. A group of 486 cancer patients receiving a fentanyl patch for pain were “genotyped for 31 single nucleotide polymorphisms in 19 genes.” The goal was to identify genetic and non-genetic predictors of pain control, cognitive dysfunction due to opiates, sickness response, and “opioid adverse event complaints.” 

They found no significant genetic connection to any of these issues with the exception of cognitive dysfunction, which had this fascinating result:

[A] major genetic predictor of cognitive dysfunction in cancer pain patients receiving transdermal fentanyl was identified. Patients carrying the MYD88 rs6853 variant allele had half the risk of developing cognitive dysfunction: an effect seen with and without accounting for non-genetic variables.

Cognitive dysfunction was measured using the Mini Mental State Examination (MMSE), which is used to assess levels of cognitive impairment from mild to severe. So this study found a connection between genetics and whether the fentanyl patch causes cognitive dysfunction. That is one marker on the path to developing a genetic understanding of addiction.

Another marker is stress. In search of a phenotype that would “help identify individuals who are most likely to abuse drugs,” researchers at Rutgers State University determined that stressing mice results in an increase in their desire for both opioids and sugar. The authors conclude:

Taken together, these results indicate that stress can act as a physiological modulator, shifting profiles of opioid abuse susceptibility depending on an individual’s history.

If I understand this chain of research correctly, it shows that stressing mice changes their genes to increase preferences for opioids and sugar. Therefore, the “50% of addiction is genetics” line becomes much more difficult if it means a stressed parent — not an addicted parent — passes down genes predisposed to favor painkillers and processed sugars.

Furthermore, if half of drug addiction is the result of genetics, most of the other half is the result of stress, as indicated in a recent article here at AddictionNews. So if half the cause for drug addiction is stress, and the genetic half is also genetic stress, then we need to look at something other than the substances themselves as the cause of addiction. We need to find and teach alternative methods for dealing with stress other than binging on food, drinks, sex, drugs, and video games. It may very well be that the genetics of addiction are the genetics of stress.

Written by Steve O’Keefe. First published July 29, 2024.

Sources:

“Marshall Researchers Studying Genetics of Fentanyl Addiction,” West Virginia Public Broadcasting, July 23, 2024.

“Fentanyl overdoses and pharmacogenetics,” Pharmacogenetics and Genomics, September 2019.

“Stress reveals a specific behavioral phenotype for opioid abuse susceptibility,” Journal of the Experimental Analysis of Behavior, February 2022.

Image used under Fair Use: Public Domain.