Why do some people develop addiction while others do not, even when exposed to similar life experiences or substances? While environment, trauma, stress, and social circumstances are all major contributors, new research increasingly suggests that biology also plays an important role.
Opioids are a group of drugs that include heroin, morphine, fentanyl, methadone, and certain prescription painkillers. They work by attaching to opioid receptors in the brain, reducing pain and often producing feelings of relaxation or euphoria. However, repeated exposure can gradually alter the brain’s reward system, increasing the risk of dependence and addiction as witnessed by the opiate crisis in America.
One of the most important systems involved in addiction is the dopamine reward pathway. Dopamine is a chemical messenger linked to pleasure, motivation, learning, and reinforcement. Activities necessary for survival – such as eating, social bonding, or achievement – naturally activate this system. Drugs such as opioids, however, stimulate it far more intensely than natural rewards, which may eventually disrupt the brain’s normal balance.
Genes and Addiction Vulnerability
Not everyone responds to opioids in the same way. Some individuals appear more vulnerable to developing compulsive patterns of use, while others do not. Part of this difference may lie in small natural variations in DNA known as genetic polymorphisms.
In my dissertation, completed in partial fulfilment of an M.Sc. in Addiction Studies at the University of Malta, under the supervision of Prof. Richard Muscat, I explored whether certain genetic differences may influence vulnerability to opioid addiction within the Maltese population. The findings add to growing international evidence that addiction is not simply a matter of willpower or personal choice, but rather a complex interaction between the brain, genetics, and environment.
The study focused on three genes involved in the brain’s reward and motivation systems. One gene influences how strongly opioids bind to receptors in the brain. Another affects dopamine signalling linked to reward sensitivity, while the third regulates the breakdown of dopamine in the prefrontal cortex – the area involved in decision-making, impulse control, and emotional regulation.
Rather than searching for a single ‘addiction gene’, my research examined whether combinations of these genetic variations could collectively increase risk. This reflects the modern understanding that addiction is polygenic, meaning it arises from the combined influence of many small biological factors rather than one defining cause.
The research compared individuals diagnosed with opioid use disorder to a Maltese control population. One particular genetic variation related to dopamine regulation showed a significant association with opioid addiction risk. More importantly, individuals carrying a greater number of the studied risk variants had significantly higher overall genetic risk scores.
First Local Study
Although the study was relatively small, the findings matter because they represent some of the first local data examining addiction genetics in Malta. Most existing studies in this field have focused on much larger international populations, particularly in the United States and Northern Europe. Understanding how these genetic factors appear within the Maltese population helps contribute to a more complete global picture of addiction vulnerability.
However, genetics alone can never fully explain addiction. Environmental influences remain essential. Trauma, childhood experiences, social isolation, mental health difficulties, chronic stress, and drug availability all interact with biology in shaping addiction risk. A person may carry certain genetic vulnerabilities and never develop addiction, while another may develop severe dependence primarily due to environmental circumstances.
This is one of the most important messages emerging from modern addiction science: biology is not destiny. Instead, genes may influence susceptibility in much the same way that certain genetic traits can increase vulnerability to conditions such as heart disease or diabetes without guaranteeing they will occur.
Understanding addiction through this broader scientific perspective may also help reduce stigma. People struggling with substance use disorders are often viewed as lacking discipline or moral character. In reality, addiction involves measurable changes in brain function, reward processing, stress systems, and behaviour. Recognising this allows society to approach addiction more compassionately and effectively as a medical and psychological condition rather than simply a personal failing. A recent book by Kathryn Paige Harden, Original Sin: On the Genetics of Vice, The Problem of Blame and the Future of Forgiveness, brings home this very point in a most elegant manner.
Practical Implications
Research into addiction genetics may also have practical implications in the future. One possible application involves identifying individuals who may be more vulnerable before prescribing opioid medications for pain management. Another possibility is the development of more personalised treatments tailored to a person’s biological profile.
While such approaches are still evolving, studies like this contribute small but important pieces to a much larger scientific puzzle. As researchers continue to investigate how genes and environment interact, the ultimate goal remains the same: improving prevention, treatment, and understanding for individuals affected by addiction.
This research was conducted as part of the Master of Science in Addiction Studies at the University of Malta. I would like to sincerely thank the Tertiary Education Scholarship Scheme (TESS) for financially supporting this research and making the successful completion of this study possible.
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