Epigenetic Influences on Addiction

In two previous posts, I introduced essential concepts of epigenetics, the role of epigenetics in mental health broadly, and reviewed research findings on epigenetic factors that increase risk of developing depressed mood, schizophrenia, and bipolar disorder.

Here, I provide a concise summary of research findings on epigenetic influences on alcohol abuse and other substance use disorders. The long-term health consequences of exposure to drugs of abuse is a subject of increasing public concern because of the opioid epidemic, the widespread use of prescription stimulants in all age groups, and increasing openness to therapeutic uses of ketamine, MDMA and Cannabis, (Wanner 2019).

Why epigenetics research is important for understanding addiction

Epigenetics research is leading to better understandings of complex physiological and neurophysiological processes that lead to addiction. These new understandings go beyond current models, which explain addiction on the basis of dysregulation of dopamine synthesis in the brain’s reward centers.

Accumulating research findings reveal complex relationships between epigenetic alterations during fetal development, early childhood, and adolescence, and increased the risk of developing substance use disorders. It has been estimated that vulnerability to developing substance use disorders is inherited via genetic and epigenetic mechanisms that operate in both the mother and father at a rate of 40 to 72 percent. Only a few animal studies have been done on opiates and alcohol however findings suggest that chronic exposure to both substances causes similar epigenetic changes in the brain resulting in addiction and possibly also increased risk of developing neuropsychiatric disorders.

Deleterious epigenetic consequences of alcohol and drugs of abuse result from both fetal exposure and adult-use

Most studies have examined the deleterious consequences of maternal substance abuse on the fetus. However paternal drug use also causes epigenetic alternations that may significantly increase the lifetime risk of developing a substance use disorder in offspring (Goldberg 2019; Wanner 2019). Maternal abuse of narcotics resulting in fetal exposure (i.e. via the placental circulation) may result in deficits in memory and accelerate aging and age-related health problems. In-utero exposure of rodents to cannabinoids has been shown to result in long-term deficits in memory and cognitive function that involve the hippocampus, frontal cortex, and other brain regions.

Findings of animal studies suggest that long-term abuse of stimulants (such as amphetamine and methamphetamine) and cocaine in adulthood induces alterations in genes that cause dysregulation in normal synthesis of neurotransmitters resulting in addiction behavior (Godino 2015). Epigenetic alterations induced by heavy drinking, cocaine, or cannabis abuse during adolescence may also increase the risk of developing drug addiction in adulthood. Even limited exposure of the adult brain to cocaine may result in significant epigenetic alterations in histones, DNA and RNA in neurons in brain regions involved in regulating the behavioral effects of cocaine. While certain epigenetic modifications result in reduced cocaine-seeking behavior, others result in hypersensitivity to cocaine. The type and severity of cocaine-induced epigenetic alterations in DNA may be related to the duration of cocaine abuse.

Bottom line

Research on the role of epigenetics in drug and alcohol abuse is still at a very early stage. Large prospective animal and human studies are needed to characterize those epigenetic alterations induced by alcohol or drug abuse that increase the risk of addiction, and to identify drugs or natural supplements that may mitigate or reverse deleterious epigenetic alterations, reducing the risk of addiction. The interested reader can refer to several recent articles for a more detailed discussion (see references).