Addiction

Addiction
Brain positron emission tomography images that compare brain metabolism in a healthy individual and an individual with a cocaine addiction
Specialty	Psychiatry, clinical psychology, toxicology, addiction medicine
Symptoms	Recurring compulsion to engage in rewarding activity despite negative consequences
Risk factors	Family history, adverse childhood experiences, attention deficit hyperactivity disorder
Treatment	Cognitive behavioral therapy, behavior modification, medication

Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can alter brain function in synapses similar to natural rewards like food or falling in love^[1] in ways that perpetuate craving and weakens self-control for people with pre-existing vulnerabilities.^[2] This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in the development of addiction.^[3][4][5] While mice given cocaine showed the compulsive and involuntary nature of addiction,^[a] for humans this is more complex, related to behavior^[6] or personality traits.^[7]

Classic signs of addiction include compulsive engagement in rewarding stimuli, preoccupation with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward),^[8][9] coupled with delayed deleterious effects (long-term costs).^[4][10]

Examples of substance addiction include alcoholism, cannabis addiction, amphetamine addiction, cocaine addiction, nicotine addiction, opioid addiction, and eating or food addiction. Behavioral addictions may include gambling addiction, shopping addiction, stalking, pornography addiction, internet addiction, social media addiction, video game addiction, and sexual addiction. The DSM-5 and ICD-10 only recognize gambling addictions as behavioral addictions, but the ICD-11 also recognizes gaming addictions.^[11]

Signs and symptoms of drug addiction can vary depending on the type of addiction. Symptoms may include:

• Continuation of drug use despite the knowledge of consequences^[12]
• Disregarding financial status when it comes to drug purchases
• Ensuring a stable supply of the drug
• Needing more of the drug over time to achieve similar effects^[12]
• Social and work life impacted due to drug use^[12]
• Unsuccessful attempts to stop drug use^[12]
• Urge to use drug regularly

Other signs and symptoms can be categorized across relevant dimensions:

Behavioral Changes	Physical Changes	Social Changes
Angry and irritable Changes to eating or sleeping habits Changes to personality and attitude Decreased attendance and performance in workplace or school setting[12] Fearful, paranoid and anxious without probable cause[13] Frequently engaging in conflicts (fights, illegal activity) Frequent or sudden changes in mood and temperament Hiding or in denial of certain behaviors Lack of motivation Periodic hyperactivity Using substances in inappropriate settings	Abnormal pupil size Bloodshot eyes Body odor Impaired motor coordination[13] Periodic tremors Poor physical appearance Slurred speech Sudden changes in weight	Changes in hobbies Changes to financial status (unexplained need for money) Legal problems related to substance abuse Sudden changes in friends and associates Use of substance despite consequences to personal relationships[13]

Addiction and dependence glossary[3][14][15]
addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose drug withdrawal – symptoms that occur upon cessation of repeated drug use physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., delirium tremens and nausea) psychological dependence – dependence that is characterised by emotional-motivational withdrawal symptoms (e.g., anhedonia and anxiety) that affect cognitive functioning. reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach sensitization – an amplified response to a stimulus resulting from repeated exposure to it substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress drug tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
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The DSM-5 discourages using the term "drug addiction" because of its "uncertain definition and its potentially negative connotation" and prefers the term "substance use disorder" to describe the wide range of the disorder, from a mild form to a severe state of chronically relapsing, compulsive pattern of drug taking.^[16]

SUD, belongs to the class of substance-related disorders, is a chronic and relapsing brain disorder that features drug seeking and drug abuse, despite their harmful effects.^[17] This form of addiction changes brain circuitry such that the brain's reward system is compromised,^[18] causing functional consequences for stress management and self-control.^[17] Damage to the functions of the organs involved can persist throughout a lifetime and cause death if untreated.^[17] Substances involved with drug addiction include alcohol, nicotine, marijuana, opioids, cocaine, amphetamines, and even foods with high fat and sugar content.^[19] Addictions can begin experimentally in social contexts^[20] and can arise from the use of prescribed medications or a variety of other measures.^[21]

It has been shown to work in phenomenological, conditioning (operant and classical), cognitive models, and the cue reactivity model. However, no one model completely illustrates substance abuse.^[22]

Risk factors for addiction include:

• Aggressive behavior (particularly in childhood)
• Availability of substance^[20]
• Community economic status^{[citation needed]}
• Experimentation^[20]
• Epigenetics
• Impulsivity (attentional, motor, or non-planning)^[23]
• Lack of parental supervision^[20]
• Lack of peer refusal skills^[20]
• Mental disorders^[20]
• Method substance is taken^[17]
• Usage of substance in youth^[20]

The diagnostic criteria for food or eating addiction has not been categorized or defined in references such as the Diagnostic and Statistical Manual of Mental Disorders (DSM or DSM-5) and is based on subjective experiences similar to substance use disorders.^[12][23] Food addiction may be found in those with eating disorders, though not all people with eating disorders have food addiction and not all of those with food addiction have a diagnosed eating disorder.^[12] Long-term frequent and excessive consumption of foods high in fat, salt, or sugar, such as chocolate, can produce an addiction^[24][25] similar to drugs since they trigger the brain's reward system, such that the individual may desire the same foods to an increasing degree over time.^[26][12][23] The signals sent when consuming highly palatable foods have the ability to counteract the body's signals for fullness and persistent cravings will result.^[26] Those who show signs of food addiction may develop food tolerances, in which they eat more, despite the food becoming less satisfactory.^[26]

Chocolate's sweet flavor and pharmacological ingredients are known to create a strong craving or feel 'addictive' by the consumer.^[27] A person who has a strong liking for chocolate may refer to themselves as a chocoholic.

Risk factors for developing food addiction include excessive overeating and impulsivity.^[23]

The Yale Food Addiction Scale (YFAS), version 2.0, is the current standard measure for assessing whether an individual exhibits signs and symptoms of food addiction.^[28][12][23] It was developed in 2009 at Yale University on the hypothesis that foods high in fat, sugar, and salt have addictive-like effects which contribute to problematic eating habits.^[29][26] The YFAS is designed to address 11 substance-related and addictive disorders (SRADs) using a 25-item self-report questionnaire, based on the diagnostic criteria for SRADs as per DSM-5.^[30][12] A potential food addiction diagnosis is predicted by the presence of at least two out of 11 SRADs and a significant impairment to daily activities.^[31]

The Barratt Impulsiveness Scale, specifically the BIS-11 scale, and the UPPS-P Impulsive Behavior subscales of Negative Urgency and Lack of Perseverance have been shown to have relation to food addiction.^[23]

The term behavioral addiction refers to a compulsion to engage in a natural reward – which is a behavior that is inherently rewarding (i.e., desirable or appealing) – despite adverse consequences.^[9][24][25] Preclinical evidence has demonstrated that marked increases in the expression of ΔFosB through repetitive and excessive exposure to a natural reward induces the same behavioral effects and neuroplasticity as occurs in a drug addiction.^{[24][32][33][34]}

Addiction can exist without psychotropic drugs, an idea that was popularized by psychologist Stanton Peele.^[35] These are termed behavioral addictions. Such addictions may be passive or active, but they commonly contain reinforcing features, which are found in most addictions.^[35] Sexual behavior, eating, gambling, playing video games, and shopping are all associated with compulsive behaviors in humans and have been shown to activate the mesolimbic pathway and other parts of the reward system.^[24] Based on this evidence, sexual addiction, gambling addiction, video game addiction, and shopping addiction are classified accordingly.^[24]

Personality theories of addiction are psychological models that associate personality traits or modes of thinking (i.e., affective states) with an individual's proclivity for developing an addiction. Data analysis demonstrates that psychological profiles of drug users and non-users have significant differences and the psychological predisposition to using different drugs may be different.^[36] Models of addiction risk that have been proposed in psychology literature include: an affect dysregulation model of positive and negative psychological affects, the reinforcement sensitivity theory of impulsiveness and behavioral inhibition, and an impulsivity model of reward sensitization and impulsiveness.^{[37][38][39][40][41]}

The transtheoretical model of change (TTM) can point to how someone may be conceptualizing their addiction and the thoughts around it, including not being aware of their addiction.^[42]

Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (i.e., internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors.^[43] Cognitive control, and particularly inhibitory control over behavior, is impaired in both addiction and attention deficit hyperactivity disorder.^[44][45] Stimulus-driven behavioral responses (i.e., stimulus control) that are associated with a particular rewarding stimulus tend to dominate one's behavior in an addiction.^[45]

In operant conditioning, behavior is influenced by outside stimulus, such as a drug. The operant conditioning theory of learning is useful in understanding why the mood-altering or stimulating consequences of drug use can reinforce continued use (an example of positive reinforcement) and why the addicted person seeks to avoid withdrawal through continued use (an example of negative reinforcement). Stimulus control is using the absence of the stimulus or presence of a reward to influence the resulting behavior.^[42]

Cognitive control is the intentional selection of thoughts, behaviors, and emotions, based on our environment. It has been shown that drugs alter the way our brains function, and its structure.^[46][18] Cognitive functions such as learning, memory, and impulse control, are affected by drugs.^[46] These effects promote drug use, as well as hinder the ability to abstain from it.^[46] The increase in dopamine release is prominent in drug use, specifically in the ventral striatum and the nucleus accumbens.^[46] Dopamine is responsible for producing pleasurable feelings, as well driving us to perform important life activities. Addictive drugs cause a significant increase in this reward system, causing a large increase in dopamine signaling as well as increase in reward-seeking behavior, in turn motivating drug use.^[46][18] This promotes the development of a maladaptive drug to stimulus relationship.^[47] Early drug use leads to these maladaptive associations, later affecting cognitive processes used for coping, which are needed to successfully abstain from them.^[46][42]

Some scholars have proposed evolutionary explanations for addiction, suggesting that vulnerabilities to substance or behavioural dependence reflect by-products or dysregulated expressions of reward and learning systems that were adaptive in ancestral environments. Classic accounts argue that purified drugs and rapid delivery methods exploit ancient motivational circuitry by providing "false fitness signals" that mimic cues once linked to survival or reproduction.^[48] Other reviews emphasise how psychoactive substances and behavioural reinforcers act on conserved mechanisms for reward, reinforcement, and emotion, which in modern settings can be overstimulated or maladapted.^[49][50] These perspectives do not replace proximate neurobiological models, but aim instead to situate contemporary patterns of vulnerability within a broader evolutionary framework.^[51][52]

A number of genetic and environmental risk factors exist for developing an addiction.^[3][53] Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction;^[3] the contribution from epigenetic risk factors to the total risk is unknown.^[53] 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 addiction.^[3] Adverse childhood events are associated with negative health outcomes, such as substance use disorder. Childhood abuse or exposure to violent crime is related to developing a mood or anxiety disorder, as well as a substance dependence risk.^[54]

Genetic factors, along with socio-environmental (e.g., psychosocial) factors, have been established as significant contributors to addiction vulnerability.^{[3][53][55][12]} Studies done on 350 hospitalized drug-dependent patients showed that over half met the criteria for alcohol abuse, with a role of familial factors being prevalent.^[56] Genetic factors account for 40–60% of the risk factors for alcoholism.^[57] Similar rates of heritability for other types of drug addiction have been indicated, specifically in genes that encode the Alpha5 Nicotinic Acetylcholine Receptor.^[58] Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction 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.^[58]

In humans, twin studies into addiction have provided some of the highest-quality evidence of this link, with results finding that if one twin is affected by addiction, the other twin is likely to be as well, and to the same substance.^[59] Further evidence of a genetic component is research findings from family studies which suggest that if one family member has a history of addiction, the chances of a relative or close family developing those same habits are much higher than one who has not been introduced to addiction at a young age.^[60]

The data implicating specific genes in the development of drug addiction is mixed for most genes. Many addiction studies that aim to identify specific genes focus on common variants with an allele frequency of greater than 5% in the general population. When associated with disease, these only confer a small amount of additional 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 additional risk in the development of the disease.^[61]

Genome-wide association studies (GWAS) are used to examine genetic associations with dependence, addiction, and drug use.^[55] 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 addiction may be involved either in adjusting brain behavior before drug experiences, subsequent to them, or both.^[62]

Environmental risk factors for addiction 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 addiction.^[3] For example, after the nationwide^[where?] outbreak of COVID-19, more people quit (vs. started) smoking; and smokers, on average, reduced the quantity of cigarettes they consumed.^[63] More generally, a number of different environmental factors have been implicated as risk factors for addiction, including various psychosocial stressors. The National Institute on Drug Abuse (NIDA) and studies cite lack of parental supervision, the prevalence of peer substance use, substance availability, and poverty as risk factors for substance use among children and adolescents.^[64][20] The brain disease model of addiction posits that an individual's exposure to an addictive drug is the most significant environmental risk factor for addiction.^[65] Many researchers, including neuroscientists, indicate that the brain disease model presents a misleading, incomplete, and potentially detrimental explanation of addiction.^[66]

The psychoanalytic theory model defines addiction as a form of defense against feelings of hopelessness and helplessness as well as a symptom of failure to regulate powerful emotions related to adverse childhood experiences (ACEs), various forms of maltreatment and dysfunction experienced in childhood. In this case, the addictive substance provides brief but total relief and positive feelings of control.^[42] 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.^[67] 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 having 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 or as a result of reduced impulse control, particularly during adolescence.^[67][20][42] Vast amounts of children who experienced abuse have gone on to have some form of addiction in their adolescence or adult life.^[68] This pathway towards addiction 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.^[68] If one has friends or peers who engage in drug use favorably, the chances of them developing an addiction increases. Family conflict and home management is a cause for one to become engaged in drug use.^[69]

According to Travis Hirschi's social control theory, adolescents with stronger attachments to family, religious, academic, and other social institutions are less likely to engage in delinquent and maladaptive behavior such as drug use leading to addiction.^[70]

Adolescence represents a period of increased vulnerability for developing an addiction.^[71] 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 addictive behavior before considering the consequences.^[72] 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.^[73][74]

Most individuals are exposed to and use addictive drugs for the first time during their teenage years.^[75] In the United States, there were just over 2.8 million new users of illicit drugs in 2013 (7,800 new users per day);^[75] among them, 54.1% were under 18 years of age.^[75] In 2011, there were approximately 20.6 million people in the United States over the age of 12 with an addiction.^[76] Over 90% of those with an addiction began drinking, smoking or using illicit drugs before the age of 18.^[76]

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.^{[77][78][79][20]} The NIDA cites early aggressive behavior as a risk factor for substance use.^[64] 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.^[80]

Epigenetics is the study of stable phenotypic changes that do not involve alterations in the DNA sequence.^[81] Illicit drug use has been found to cause epigenetic changes in DNA methylation, as well as chromatin remodeling.^[82] The epigenetic state of chromatin may pose as a risk for the development of substance addictions.^[82] It has been found that emotional stressors, as well as social adversities may lead to an initial epigenetic response, which causes an alteration to the reward-signalling pathways.^[82] This change may predispose one to experience a positive response to drug use.^[82]

Epigenetic genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual:^[53] they 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).^[53] In addiction, epigenetic mechanisms play a central role in the pathophysiology of the disease;^[3] it has been noted that some of the alterations to the epigenome which arise through chronic exposure to addictive stimuli during an addiction 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).^[53][83]

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.^[53] With respect to addiction, more research is needed to determine the specific heritable epigenetic alterations that arise from various forms of addiction in humans and the corresponding behavioral phenotypes from these epigenetic alterations that occur in human offspring.^[53][83] Based on preclinical evidence from animal research, certain addiction-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 addiction.^{[note 1][53]} More generally, the heritable behavioral phenotypes that are derived from addiction-induced epigenetic alterations and transmitted from parent to offspring may serve to either increase or decrease the offspring's risk of developing an addiction.^[53][83]

Addiction is a disorder of the brain's reward system developing through transcriptional and epigenetic mechanisms as a result of chronically high levels of exposure to an addictive stimulus (e.g., eating food, the use of cocaine, engagement in sexual activity, participation in high-thrill cultural activities such as gambling, etc.) over extended time.^[3][84][24] DeltaFosB (ΔFosB), a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions.^{[84][24][85][25]} Two decades of research into ΔFosB's role in addiction have demonstrated that addiction arises, and the associated compulsive behavior intensifies or attenuates, along with the overexpression of ΔFosB in the D1-type medium spiny neurons of the nucleus accumbens.^{[3][84][24][85]} Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker.^[3][84][85] ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.^{[note 2][3][84]}

Transcription factor glossary
gene expression – the process by which information from a gene is used in the synthesis of a functional gene product such as a protein transcription – the process of making messenger RNA (mRNA) from a DNA template by RNA polymerase transcription factor – a protein that binds to DNA and regulates gene expression by promoting or suppressing transcription transcriptional regulation – controlling the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA upregulation, activation, or promotion – increase the rate of gene transcription downregulation, repression, or suppression – decrease the rate of gene transcription coactivator – a protein (or a small molecule) that works with transcription factors to increase the rate of gene transcription corepressor – a protein (or a small molecule) that works with transcription factors to decrease the rate of gene transcription response element – a specific sequence of DNA that a transcription factor binds to
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