Written by Paul Yousif, Edited by Nikhil Chakravarty, MPH, Edited by Courtney Coleman
Substance use disorders (SUD) are mental illnesses characterized by chronic changes in the brain and impairment in functioning, most often brought on by the regular use of alcohol, drugs, and other psychoactive substances, regardless of the negative consequences. Most, if not all, public health agencies in the country categorize the continual increase in SUD cases and the proliferation of addiction as a serious public health issue.
Since 1999, the amount of substance-related deaths has increased, averaging about 100,000 recorded cases per year since 2020. Data also reveals that, in 2022 and 2023, around 17% of individuals in the US had at least one SUD, and almost 3% of the population suffered from multiple; however, research into the genetic and environmental bases of addiction, relapse, and the specific effects of substances on the brain is becoming widespread as one of the main strategies to curb SUD diagnoses and deaths.
According to American Addiction Centers (AAC), 40-60% of the risk involving developing a SUD is due to genetics and environmental factors. The genetic variants you receive from your parents cause certain genes to vary in expression and inactivation, and these changes can have dramatic effects on the brain’s reward pathway, which can cause certain individuals to be more or less prone to addiction. For instance, people who have lower levels of expression of the gene ADH1B, which breaks down alcohol, have more severe hangovers and will therefore have a lower chance of developing an alcohol use disorder. The large influx of SUD cases in the last decade has led to the initiative to discover “addiction genes,” – genes that in some way make it more or less vulnerable to developing addictions.
Because genes are passed down through generations, susceptibility to a certain SUD can “run in the family.” However, genes are not the only determining factor in developing a substance dependency; environmental factors also contribute to the risk of addiction. Besides the direct influences (e.g., the people you associate with, peer pressure, and your local community) environmental factors can actually have an immense influence on your genes as well. This is called epigenetics: non-permanent, environmentally-derived changes to DNA that can alter the expression of genes. The most profound contributor to these changes is undoubtedly stress. Encountering stress, especially long-lasting, causes numerous changes in your gene expression and impacts almost every bodily system, especially the reward pathway. For example, living in a discriminatory environment is a prevalent activator of stress, and people who live in these unfortunate conditions turn to substances to try to escape that horrible reality. Victims of events such as job loss, divorce, and the death of a loved one are also seen turning to alcohol or other substances to try to take the edge off. These changes can make the brain much more sensitive to the positive reinforcement gained from substances and increase the motivation to use them based on that. Additionally, stress hinders coping mechanisms which makes it easier to develop addiction, harder to stop, and increases the chance of relapsing.
Environmental effects that alter gene expression are most prevalent in childhood. Trauma, stress, poor parenting, and other factors can make a person much more vulnerable to SUDs. Children’s brains are very “plastic” and sensitive to the environment, which is why experiencing high levels of stress in youth will cause methylation (inactivation) of important genes that are required for processing stress and its connection to the reward pathway. A landmark study in 2010 revealed that, “The level of substance use, particularly cocaine, strongly correlated with levels of childhood physical, sexual, and emotional abuse...”. The culprit of the increase in usage, exposed by the researchers, is due to changes in brain structure and function that leave victims more susceptible to addiction, schizophrenia, and other illnesses related to dopamine and the reward pathway.
Research Leads to Results
What is the purpose of all of this research and discovery? How does knowledge of what genes impact SUDs help prevent them? Knowing which genes are specifically impacted gives pharmaceutical scientists insight into the molecular mechanisms actually underlying addiction. This allows for treatments to be developed that can inhibit these mechanisms and revert the negative impact they have. The main goal is to revert the brain reward pathways to normality in order to curb any increased chance of developing a dependency. In a landmark study, an antibody that traps methamphetamine and blocks it from entering the brain was developed by InterveXion Therapeutics. This would heavily decrease the impact of meth on the body and reduce the chance of overdose.
Bibliography
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CDC. Provisional Drug Overdose Data. CDC. Published 2024. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
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Prevalence Data 2023. Mental Health America. https://mhanational.org/issues/2023/mental-health-america-prevalence-data
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This post is not a substitute for professional advice. If you believe that you may be experiencing a medical emergency, please contact your primary care physician, or go to the nearest Emergency Room. Results from ongoing research is constantly evolving. This post contains information that was last updated on December 24, 2024.
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