The American Society of Addiction Medicine defines addiction like this: “Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.
Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.” 
Like other chronic disorders, risks for developing the disease of addiction are complex, and include genetic and environmental factors.
Opioid addiction is highly heritable, which means the genes we inherit play a strong role in determining who develops this disease. Experts estimate opioid addiction heritability at about 70%, meaning more than half the risk of getting this disease is genetic.
Now let’s talk specifics.
We all have genes that code for the structure and function of the mu opioid receptor. This receptor, when acted upon by an opioid medication, activates cellular events that create pain relief and euphoria. One gene for the opioid receptor is called OPRM1. This gene varies a little bit between people, and the varieties are called polymorphisms, from the Greek for “many forms.” In other words, my gene for the opioid receptor may be different from another person’s gene for this same receptor. Plus, each person has two copies of each gene, so I inherited one polymorphism from my dad and one from my mom, and they could be the same form of the gene or slightly different forms of this same gene. These two forms of the same gene are called “alleles.””
We know that one polymorphism of the OPRM1 gene, called 118A>G, found in around 15% of whites, causes a three-fold increase in binding of endorphins, our bodies’ natural opioids. This gene is associated with an increased risk of addiction to opioids, and variations of responses to opioids.
This means that someone with the AG variety of the OPRM1 gene is more likely to become addicted to opioids, and the sensation that person gets when taking opioids is different from people with other forms of this gene.
Still, association doesn’t necessarily mean causation. We still don’t have enough evidence to say this gene causes opioid addiction, though the gene’s presence is at least associated with opioid addiction.
Let’s turn now to the COMT gene. This gene codes for catechol-o-methyltransferase, which is an enzyme which metabolizes catecholamines in the nervous system.
Catecholamines are the chemicals in the body that are all made from the amino acid tyrosine, and the most common are epinephrine, norepinephrine, and …our old friend dopamine, the pleasure chemical.
Epi- and norepinephrine are the fight or flight chemicals released when we are stressed. Dopamine is the chemical released in the pleasure centers of the brain when we do pleasurable things like eat or have sex. Or use addicting drugs like opioids, nicotine, alcohol, benzodiazepines, cocaine, methamphetamine, or marijuana.
This COMT enzyme inactivates catecholamines including dopamine. Just like the gene coding for the opioid receptor, this gene has different varieties, or polymorphisms. At least one polymorphism is associated with upregulation of mu opioid receptors. Past studies have shown people with this polymorphism need more morphine to treat pain than people without this polymorphism. This difference may also influence the risk of opioid addiction.
Our genetics are not our destiny, however. Certain genes make addiction more likely, but there are others factors that influence risk.
For example, let’s say Jane Doe inherited all of the genes that are associated with increased risk for opioid addiction. Let’s say she got a genetic double whammy, and inherited risky genes from both sides of the family. But Jane grew up in an area where illicit opioids can’t be found. Jane remained healthy, and never had to take opioids in her whole life. Now at age 80, she’s never developed opioid addiction, even though she’s always been at much increased risk than the average person.
Let’s say Jane has a friend named Mary, who inherited all the genes that put her at low risk for addiction. But she was plagued with painful medical problems that required prescription opioids for a few years as a teenager. She also grew up in an area where adolescents had access to a wide variety of drugs including opioids. Because she missed high school often due to her medical condition, she made low grades in school. As a result, she became discouraged with school and started hanging out with drug -using peers. Eventually, Jane started misusing opioids and eventually she developed opioid addiction.
This example illustrates how environmental factors interact with genetic factors to influence risk of addiction, as ASAM pointed out in their definition of addiction.
Let’s remember people face all kinds of environmental and genetic challenges. Stress and negative life experiences increase the risk of addiction. Before we judge someone for having an addiction, let’s remember we don’t know what genetics that person has, or what challenges they’ve faced.
Anyone can become addicted to opioids, given the right circumstances.