There are a number of genetic and environmental risk factors for developing an<unk> , that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an<unk> ; the contribution from epigenetic risk factors to the total risk is unknown. Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time (e.g., weeks–months) can result in an<unk> . Genetic factors Genetic factors, along with environmental (e.g., psychosocial) factors, have been established as significant contributors to<unk>  vulnerability. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug<unk>  have been indicated by other studies, specifically in genes that encode the Alpha5 Nicotinic Acetylcholine Receptor. Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to<unk>  in several ways. For example, altered levels of a normal protein due to environmental factors may change the structure or functioning of specific brain neurons during development. These altered brain neurons could affect the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genetic expression. In humans, twin studies into<unk>  have provided some of the highest-quality evidence of this link, with results finding that if one twin is affected by<unk> , the other twin is likely to be as well, and often to the same substance. Further evidence of a genetic component is research findings from family studies which suggest that if one family member has a history of<unk> , the chances of a relative or close family developing those same habits are much higher than one who has not been introduced to<unk>  at a young age. However, the data implicating specific genes in the development of drug<unk>  is mixed for most genes. Many<unk>  studies that aim to identify specific genes focus on common variants with an allele frequency of greater than 5% in the general population; however, when associated with disease, these only confer a small amount of<unk> al risk with an odds ratio of 1.1–1.3 percent; this has led to the development the rare variant hypothesis, which states that genes with low frequencies in the population (<1%) confer much greater<unk> al risk in the development of the disease. Genome-wide association studies (GWAS) are used to examine genetic associations with dependence,<unk> , and drug use; however, these studies rarely identify genes from proteins previously described via animal knockout models and candidate gene analysis. Instead, large percentages of genes involved in processes such as cell adhesion are commonly identified. The important effects of endophenotypes are typically not capable of being captured by these methods. Genes identified in GWAS for drug<unk>  may be involved either in adjusting brain behavior prior to drug experiences, subsequent to them, or both. Environmental factors Environmental risk factors for<unk>  are the experiences of an individual during their lifetime that interact with the individual's genetic composition to increase or decrease his or her vulnerability to<unk> . For example, after the nationwide outbreak of COVID-19, more people quit (vs. started) smoking; and smokers, on average, reduced the quantity of cigarettes they consumed. More generally, a number of different environmental factors have been implicated as risk factors for<unk> , including various psychosocial stressors. The National Institute on Drug Abuse (NIDA) cites lack of parental supervision, the prevalence of peer substance use, drug availability, and poverty as risk factors for substance use among children and adolescents. The brain disease model of<unk>  posits that an individual's exposure to an addictive drug is the most significant environmental risk factor for<unk> . However, many researchers, including neuroscientists, indicate that the brain disease model presents a misleading, incomplete, and potentially detrimental explanation of<unk> . Adverse childhood experiences (ACEs) are various forms of maltreatment and household dysfunction experienced in childhood. The Adverse Childhood Experiences Study by the Centers for Disease Control and Prevention has shown a strong dose–response relationship between ACEs and numerous health, social, and behavioral problems throughout a person's lifespan, including substance use disorder. Children's neurological development can be permanently disrupted when they are chronically exposed to stressful events such as physical, emotional, or sexual abuse, physical or emotional neglect, witnessing violence in the household, or a parent being incarcerated or suffering from a mental illness. As a result, the child's cognitive functioning or ability to cope with negative or disruptive emotions may be impaired. Over time, the child may adopt substance use as a coping mechanism, particularly during adolescence. A study of 900 court cases involving children who experienced abuse found that a vast amount of them went on to suffer from some form of<unk>  in their adolescence or adult life. This pathway towards<unk>  that is opened through stressful experiences during childhood can be avoided by a change in environmental factors throughout an individual's life and opportunities of professional help. If one has friends or peers who engage in drug use favorably, the chances of them developing an<unk>  increases. Family conflict and home management is also a cause for one to become engaged in alcohol or other drug use. Age Adolescence represents a period of unique vulnerability for developing an<unk> . In adolescence, the incentive-rewards systems in the brain mature well before the cognitive control center. This consequentially grants the incentive-rewards systems a disproportionate amount of power in the behavioral decision-making process. Therefore, adolescents are increasingly likely to act on their impulses and engage in risky, potentially<unk> g behavior before considering the consequences. Not only are adolescents more likely to initiate and maintain drug use, but once addicted they are more resistant to treatment and more liable to relapse. Most individuals are exposed to and use addictive drugs for the first time during their teenage years. In the United States, there were just over 2.8 million new users of illicit drugs in 2013 (~7,800 new users per day); among them, 54.1% were under 18 years of age. In 2011, there were approximately 20.6 million people in the United States over the age of 12 with an<unk> . Over 90% of those with an<unk>  began drinking, smoking or using illicit drugs before the age of 18. Comorbid disorders Individuals with comorbid (i.e., co-occurring) mental health disorders such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) or post-traumatic stress disorder are more likely to develop substance use disorders. The cites early aggressive behavior as a risk factor for substance use. A study by the National Bureau of Economic Research found that there is a "definite connection between mental illness and the use of addictive substances" and a majority of mental health patients participate in the use of these substances: 38% alcohol, 44% cocaine, and 40% cigarettes. Epigenetic Transgenerational epigenetic inheritance Epigenetic genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual; they also serve as the mechanism responsible for transgenerational epigenetic inheritance, a phenomenon in which environmental influences on the genes of a parent can affect the associated traits and behavioral phenotypes of their offspring (e.g., behavioral responses to environmental stimuli). In<unk> , epigenetic mechanisms play a central role in the pathophysiology of the disease; it has been noted that some of the alterations to the epigenome which arise through chronic exposure to addictive stimuli during an<unk>  can be transmitted across generations, in turn affecting the behavior of one's children (e.g., the child's behavioral responses to addictive drugs and natural rewards). The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include DNA methylation, histone modifications, and downregulation or upregulation of microRNAs. With respect to<unk> , more research is needed to determine the specific heritable epigenetic alterations that arise from various forms of<unk>  in humans and the corresponding behavioral phenotypes from these epigenetic alterations that occur in human offspring. Based upon preclinical evidence from animal research, certain<unk> -induced epigenetic alterations in rats can be transmitted from parent to offspring and produce behavioral phenotypes that decrease the offspring's risk of developing an<unk> . More generally, the heritable behavioral phenotypes that are derived from<unk> -induced epigenetic alterations and transmitted from parent to offspring may serve to either increase or decrease the offspring's risk of developing an<unk> .
Addiction
Amphetamine dependence
Behavioral addiction
Cocaine dependence
Polysubstance dependence
Benzodiazepine dependence
Substance dependence
Suicide