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Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use often alters
brain function A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ver ...
in ways that perpetuate craving, and weakens (but does not completely negate)
self-control Self-control, an aspect of inhibitory control, is the ability to regulate one's emotions, thoughts, and behavior in the face of temptations and impulses. As an executive function, it is a cognitive process that is necessary for regulating one' ...
. This phenomenon – drugs reshaping
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
function – has led to an understanding of addiction as a brain disorder with a complex variety of
psychosocial The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...
as well as neurobiological (and thus involuntary) factors that are implicated in addiction's development. 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 Gratification is the pleasurable emotional reaction of happiness in response to a fulfillment of a desire or goal. It is also identified as a response stemming from the fulfillment of social needs such as affiliation, socializing, social approva ...
(short-term reward), coupled with delayed deleterious effects (long-term costs). Examples of drug (or more generally, substance) addictions include
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
, marijuana addiction,
amphetamine addiction Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used a ...
,
cocaine addiction Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of coc ...
, nicotine addiction,
opioid addiction Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Op ...
, and eating or
food addiction A food or eating addiction is any behavioral addiction that is primarily characterized by the compulsive consumption of palatable (e.g., high fat and high sugar) food items which markedly activate the reward system in humans and other anim ...
. Alternatively, behavioural addictions may include gambling addiction, internet addiction,
video game addiction Video game addiction (VGA), also known as gaming disorder or internet gaming disorder, is generally defined as the problematic, compulsive use of video games that results in significant impairment to an individual's ability to function in vario ...
,
pornography addiction Pornography addiction is the controversial application of an addiction model to the use of pornography. Pornography may be part of compulsive sexual behavior with negative consequences to one's physical, mental, social, or financial well-being. W ...
and
sexual addiction According to proponents of the concept, sexual addiction, also known as sex addiction, is a state characterized by compulsive participation or engagement in sexual activity, particularly sexual intercourse, despite negative consequences. The c ...
. The only behavioral addiction recognized by the
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
and the ICD-10 is gambling addiction. With the introduction of the ICD-11 gaming addiction was appended. The term "addiction" is frequently misused when referring to other compulsive behaviors or disorders, particularly dependence, in news media. An important distinction between drug addiction and dependence is that drug dependence is a disorder in which cessation of drug use results in an unpleasant state of withdrawal, which can lead to further drug use. Addiction is the compulsive use of a substance or performance of a behavior that is independent of withdrawal. Addiction can occur in the absence of dependence, and dependence can occur in the absence of addiction, although the two often occur together.


Drug or substance addiction

Drug addiction, also known as substance use disorders, is a chronic and relapsing brain disorder that features drug seeking and drug abuse, despite their harmful effects. This form addiction changes brain circuitry such that the brain's reward system is compromised, causing functional consequences to stress management and self-control. Damage to the functions of the organs involved can persist throughout a lifetime and can cause death, if untreated. Substances involved with drug addiction include; alcohol, nicotine, marijuana, opioids, cocaine, heroin, methamphetamines, and even foods with high fat and sugar content. Drug addictions can begin experimentally in social contexts, can arise from use of prescribed medications or a variety of other measures. Risk factors for Drug addiction includes: * Aggressive behavior (particularly in childhood) * Absent/lack of parental supervision * Lack of peer refusal skills * Drug experimentation * Availability of drugs * Community economic status * Mental disorders * Epigenetics * Usage of drugs in youth * Method drug is taken


Food addiction

Reviews of preclinical studies indicate that long-term frequent and excessive consumption of high fat or sugar foods can produce an addiction. Similarly to addictive drugs, foods high in fat and sugar trigger the brain's reward/pleasure centers, such that the individual may desire the same foods to an increasing degree over time. The signals sent when consuming highly palatable foods have the ability to counteract the body's signals for fullness, leading to persistent cravings. Those who show signs of food addiction may develop food tolerances, in which they eat more, despite the food becoming less satisfactory. Chocolate is a food that can cause a food addiction. Chocolate's sweet flavor and pharmacological ingredients is known to create a strong craving or feel 'addictive' by the consumer. A person who has a strong liking for chocolate may refer to themselves as a
chocoholic A chocoholic is a person who craves or compulsively consumes chocolate. The word "chocoholic" was first used in 1968, according to Merriam-Webster. It is a portmanteau of "chocolate" and "alcoholic". The term is used loosely or humorously to des ...
. Chocolate is not yet formally recognized by the DSM-5 as a diagnosable addiction. 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. It was developed in 2009 at
Yale University Yale University is a Private university, private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the List of Colonial Colleges, third-oldest institution of higher education in the United Sta ...
on the hypothesis that foods high in fat, sugar, and salt have addictive-like effects which contribute to problematic eating habits. The YFAS is designed to address 11 substance-related and addictive disorders (SRADs) using a 35-item questionnaire, based on the diagnostic criteria for SRADs as per DSM-5. A potential food addiction diagnosis is predicted by the presence of at least 2 out of 11 SRADs and a significant impairment to daily activities.


Behavioral addiction

The term "behavioral addiction" refers to a
compulsion Compulsion may refer to: * Compulsive behavior, a psychological condition in which a person does a behavior compulsively, having an overwhelming feeling that they must do so. * Obsessive–compulsive disorder, a mental disorder characterized by i ...
to engage in a natural reward – which is a behavior that is inherently rewarding (i.e., desirable or appealing) – despite adverse consequences. 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 Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...
as occurs in a drug addiction. Addiction can exist in the absence of psychotropic drugs, which was popularized by Peele. These are termed behavioural addictions. Such addictions may be passive or active, but they commonly contain reinforcing features, which are found in most addictions. Sexual behavior, eating, gambling, playing video games, and shopping are all associated with compulsive behaviors in humans and have also been shown to activate the mesolimbic pathway and other parts of the reward system. Based upon this evidence,
sexual addiction According to proponents of the concept, sexual addiction, also known as sex addiction, is a state characterized by compulsive participation or engagement in sexual activity, particularly sexual intercourse, despite negative consequences. The c ...
, gambling addiction,
video game addiction Video game addiction (VGA), also known as gaming disorder or internet gaming disorder, is generally defined as the problematic, compulsive use of video games that results in significant impairment to an individual's ability to function in vario ...
, and
shopping addiction Shopping addiction is characterized by an eagerness to purchase unnecessary or superfluous things and a lack of impulse control when it comes to shopping. It is a concept similar to compulsive buying disorder (''oniomania''), but usually has a mor ...
are classified accordingly.


Sexual

Sexual addiction According to proponents of the concept, sexual addiction, also known as sex addiction, is a state characterized by compulsive participation or engagement in sexual activity, particularly sexual intercourse, despite negative consequences. The c ...
involves an engagement in excessive, compulsive, or otherwise problematic sexual behaviour that persists despite negative physiological, psychological, social, and occupational consequences. Sexual addiction may also be referred to as
hypersexuality Hypersexuality is extremely frequent or suddenly increased libido. It is controversial whether it should be included as a clinical diagnosis used by mental healthcare professionals. Nymphomania and satyriasis were terms previously used for the c ...
or compulsive sexual behavior disorder. The
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
does not recognize sexual addiction as a clinical diagnosis. Hypersexuality disorder and internet addiction disorder were among proposed additions to the DSM-5, but were later rejected due to the insufficient evidence available in support of the existence of these disorders as discrete mental health conditions. Reviews of both clinical research in humans and preclinical studies involving ΔFosB have identified compulsive sexual activity – specifically, any form of sexual intercourse – as an addiction (i.e.,
sexual addiction According to proponents of the concept, sexual addiction, also known as sex addiction, is a state characterized by compulsive participation or engagement in sexual activity, particularly sexual intercourse, despite negative consequences. The c ...
). Moreover, reward cross-sensitization between amphetamine and sexual activity, meaning that exposure to one increases the desire for both, has been shown to occur preclinically and clinically as a dopamine dysregulation syndrome; ΔFosB
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
is required for this cross-sensitization effect, which intensifies with the level of ΔFosB expression.


Gambling

Gambling Gambling (also known as betting or gaming) is the wagering of something of value ("the stakes") on a random event with the intent of winning something else of value, where instances of strategy are discounted. Gambling thus requires three el ...
provides a natural reward that is associated with compulsive behavior. There is evidence from functional
neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incr ...
that gambling activates the reward system and the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
in particular. It is known that dopamine is involved in learning, motivation, as well as the reward system. The exact role of dopamine in gambling addiction has been debated. Suggested roles for D2, D3, and D4
dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
s, as well as D3 receptors in the substantia nigra have been found in rat and human models, showing a correlation with the severity of the gambling behavior. This in turn was linked with greater dopamine release in the
dorsal striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutama ...
. Research has shown that gambling addictions are linked with
comorbidities In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
such as mental health disorders, substance abuse, or even personality disorders. There have been studies that show a high prevalence of alcohol use disorder and
drug use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and b ...
in compulsive gamblers. Risk factors for gambling addictions include: * Young age * Substance use * Antisocial behavior * Male * Impulsive personality, and * Sensation seeking. Gambling addiction has been associated with some personality traits, including: harm avoidance, low self direction, decision making and planning insufficiencies, impulsivity, as well as sensation seeking individuals. Although some personality traits can be linked with gambling addiction, there is no general description of gambling addicted individuals.


Internet

Internet addiction is not a medically recognized addictive disorder. Debate over the classification of problematic internet use considers whether it should be thought of as a behavioural addiction, an impulse control disorder, or an obsessive-compulsive disorder. Others argue that internet addiction should be considered a symptom of an underlying mental health condition and not a disorder in itself. Internet addiction is described as excessive use of the internet for nonessential reasons unrelated to occupational or academic requirements. Problematic internet use may include a preoccupation with the internet and/or digital media, excessive time spent using the internet despite resultant distress in the individual, increase in the amount of internet use required to achieve the same desired emotional response, loss of control over one's internet use habits, withdrawal symptoms, and continued problematic internet use despite negative consequences to one's work, social, academic, or personal life. Studies conducted in the United States, Asia, and Europe have identified Internet addiction prevalence rates ranging in value from 1% to 18%, with the adolescent population having high rates compared to other age groups. However, prevalence rates have been difficult to establish due to a lack of universally accepted diagnostic criteria, a lack of diagnostic instruments demonstrating cross-cultural validity and reliability, and existing controversy surrounding the validity of labelling problematic internet use as an addictive disorder. People with Internet addiction are likely to have a comorbid psychiatric disorder. Comorbid diagnoses identified alongside internet addiction include affective mood disorders, anxiety disorders, substance use disorders, and attention deficit hyperactivity disorder.


Video games

Video game addiction Video game addiction (VGA), also known as gaming disorder or internet gaming disorder, is generally defined as the problematic, compulsive use of video games that results in significant impairment to an individual's ability to function in vario ...
is characterized by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
as excessive gaming behavior, potentially prioritized over other interests, despite the negative consequences that may arise, for a period of at least 12 months. In May 2019, the World Health Organization introduced gaming disorder in the 11th edition of the International Classification of Diseases. Video game addiction has been shown to be more prevalent in males than females, higher by 2.9 times. It has been suggested that people of younger ages are more prone to become addicted to video games. This may be due to video games being relatively new, hence the higher prevalence in younger groups. People with certain personalities may be more susceptible to gaming addictions, however, there have been conflicting results on this topic. Risk factors for video game addiction include: * Male * Psychopathologies (e.g. ADHD or MDD) * Social anxiety


Shopping

Shopping addiction Shopping addiction is characterized by an eagerness to purchase unnecessary or superfluous things and a lack of impulse control when it comes to shopping. It is a concept similar to compulsive buying disorder (''oniomania''), but usually has a mor ...
, or compulsive buying disorder (CBD), is the excessive urge to shop or spend, potentially leading to unwanted consequences. These consequences can have serious impacts, such as increased
consumer debt In economics, consumer debt is the amount owed by consumers (as opposed to amounts owed by businesses or governments). It includes debts incurred on purchase of goods that are consumable and/or do not appreciate. In macroeconomic terms, it is ...
, negatively affected relationships, increased risk of illegal behavior, and suicide attempts. Shopping addiction occurs worldwide and has shown a 5.8% prevalence in the United States. Similar to other behavioural addictions, a study has found CBD can be linked to mood disorders, substance use disorders, eating disorders, and other disorders involving a lack of control.


Signs and symptoms

Signs and symptoms of addiction can vary depending on the type of addiction. Symptoms of drug addictions may include: * Urge to use drug regularly * Needing more of the drug over time to achieve similar effects * Ensuring a stable supply of the drug * Disregarding financial status when it comes to drug purchases * Social and work life impacted due to drug use * Continuation of drug use despite the knowledge of consequences * Unsuccessful attempts to stop drug use * Experiencing withdrawal symptoms when stopping the drug Observable signs and symptoms of drug addiction include:


Screening and assessment


Addictions neuroclinical assessment (ANA)

The addictions neuroclinical assessment is used to diagnose addiction disorders. This tool measures 3 different domains. The three neurofunctional domains include, executive function, incentive salience, and negative emotionality. The executive function domain includes processes that are involved in organizing behaviour towards future goals. Some of these processes include attention, response inhibition, behavioural flexibility, working memory, and planning. These are processes that would be disrupted in addiction. The second domain, incentive salience, is the psychological process which can change we perceive stimuli. In the case of addiction, making the stimuli attractive. The last domain involved in this assessment is negative emotionality. The increase in negative emotional responses has been commonly found with individuals with addictions. Researchers have considered that the excessive consumption of substances may be due to this negative effect, in hopes of reducing it.


Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS)

This is a screening and assessment tool in one, assessing commonly used substances. This tool allows for a simple diagnosis, eliminating the need for several screening and assessment tools, as it includes both TAPS-1 and TAPS-2, screening and assessment tools respectively. The screening component asks about the frequency of use of the specific substance (tobacco, alcohol, prescription medication, and other). If an individual screens positive, then the second component begins. This dictates the risk level of the substance.


CRAFFT 2.0

The CRAFFT is an efficient and effective screening tool that is used universally in different medical centres. This tool is used to identify substance use, substance related driving risk, and addictions amongst youth. This tool utilizes a set of questions for different scenarios. In the case of a specific combination of answers, different question sets can be used to yield a more accurate answer. After the questions, the
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
criteria are used to identify the likelihood of the person having substance use disorder. After these tests are done, the clinician is to give the "5 RS" of brief counselling. The 5 RS of brief counselling includes: # REVIEW screening results # RECOMMEND to not use # RIDING/DRIVING risk counselling # RESPONSE: elicit self-motivational statements # REINFORCE self-efficacy


Drug Abuse Screening Test (DAST-10)

The Drug Abuse Screening Test (DAST) is a self-reporting tool that measures problematic substance use. Responses to this test are recorded as yes or no answers, and scored as a number between 0 to 28. Drug abuse or dependance, are indicated by a cut off score of 6. There are currently three versions of this screening tool, DAST-28, DAST-20, and DAST-10. Each of these instruments are copyrighted by Dr. Harvey A. Skinner.


Alcohol, Smoking, and Substance Involvement Test (ASSIST)

The Alcohol, Smoking, and Substance Involvement Test (ASSIST) is an interview-based questionnaire consisting of 8 questions developed by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
. The questions ask about lifetime use; frequency of use; urge to use; frequency of health, financial, social, or legal problems related to use; failure to preform duties; if anyone has raised concerns over use; attempts to limit or moderate use; and use by injection.


Causes


Personality theories

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 there is a significant difference in the psychological profiles of drug users and non-users and the psychological predisposition to using different drugs may be different. 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 Reinforcement sensitivity theory (RST) proposes three brain-behavioral systems that underlie individual differences in sensitivity to reward, punishment, and motivation. While not originally defined as a theory of personality, the RST has been use ...
model of impulsiveness and behavioral inhibition, and an impulsivity model of
reward sensitization Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
and impulsiveness.


Neuropsychology

Cognitive control In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and suc ...
and stimulus control, which is associated with operant and
classical conditioning Classical conditioning (also known as Pavlovian or respondent conditioning) is a behavioral procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a triangle). It also refers to the learni ...
, represent opposite processes (i.e., internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors. Cognitive control, and particularly inhibitory control over behavior, is impaired in both addiction and
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
. 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.


Stimulus control of behavior


Cognitive control of behavior

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


Risk factors

There are a number of genetic and environmental risk factors for developing an addiction, that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction; 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 addiction. Adverse childhood events are associated with negative health outcomes, such as substance use disorder. Studies show that childhood abuse or exposure to violent crime was positively related to developing a mood or anxiety disorder, as well as a substance dependence risk.


Genetic factors

Genetic factors, along with environmental (e.g., psychosocial) factors, have been established as significant contributors to addiction vulnerability. 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. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
. Similar rates of heritability for other types of drug addiction 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 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. 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 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 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. However, 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; however, 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.
Genome-wide association studies In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any varian ...
(GWAS) are used to examine genetic associations with dependence, addiction, 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 addiction may be involved either in adjusting brain behavior prior to drug experiences, subsequent to them, or both.


Environmental factors

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. 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 addiction, 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 addiction posits that an individual's exposure to an addictive drug is the most significant environmental risk factor for addiction. However, many researchers, including neuroscientists, indicate that the brain disease model presents a misleading, incomplete, and potentially detrimental explanation of addiction. Adverse childhood experiences (ACEs) are various forms of
maltreatment Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...
and household dysfunction experienced in childhood. The Adverse Childhood Experiences Study by the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
has shown a strong
dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure tim ...
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 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, particularly during adolescence. A study of 900 court cases involving children who experienced abuse found that a vast amount of them went on to have some form of addiction in their adolescence or adult life. 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. 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 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 addiction. 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 addicting 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 addiction. Over 90% of those with an addiction began drinking, smoking or using illicit drugs before the age of 18.


Comorbid disorders

Individuals with comorbid (i.e., co-occurring)
mental health Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental hea ...
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 The National Bureau of Economic Research (NBER) is an American private nonprofit research organization "committed to undertaking and disseminating unbiased economic research among public policymakers, business professionals, and the academic c ...
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

Epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are ...
is the study of stable phenotypic changes that do not involve alterations in the DNA sequence. Illicit drug use has been found to cause epigenetic changes in DNA methylation, as well as
chromatin remodelling Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
. The epigenetic state of chromatin may pose as a risk for the development of substance addictions. 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. This change may predispose one to experience a positive response to drug use.


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 phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prope ...
s of their offspring (e.g., behavioral responses to environmental stimuli). In addiction, epigenetic mechanisms play a central role in the pathophysiology of the disease; it has been noted that some of the alterations to the
epigenome An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes 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). The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include DNA methylation, histone modifications, and downregulation or upregulation of
microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. mi ...
s. With respect to addiction, more research is needed to determine the specific
heritable Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...
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. Based upon preclinical evidence from
animal research Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
, 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. 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.


Mechanisms

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. DeltaFosB (ΔFosB), a gene
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions. 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. Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
. ΔFosB expression in these neurons directly and positively regulates drug self-administration and
reward sensitization Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
through
positive reinforcement In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher fr ...
, while decreasing sensitivity to aversion. Chronic addictive drug use causes alterations in gene expression in the mesocorticolimbic projection. The most important
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
s that produce these alterations are ΔFosB, cAMP response element binding protein (
CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first de ...
), and nuclear factor kappa B (
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
). ΔFosB is the most significant biomolecular mechanism in addiction because the overexpression of ΔFosB in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and behavioral effects (e.g., expression-dependent increases in drug self-administration and
reward sensitization Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
) seen in drug addiction. ΔFosB expression in nucleus accumbens D1-type medium spiny neurons directly and positively regulates drug self-administration and
reward sensitization Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
through
positive reinforcement In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher fr ...
while decreasing sensitivity to aversion. ΔFosB has been implicated in mediating addictions to many different drugs and drug classes, including alcohol, amphetamine and other
substituted amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...
,
cannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
s,
cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...
,
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...
,
nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
,
opiates An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonist ...
, phenylcyclidine, and propofol, among others.
ΔJunD Under the early Caliphates, a ''jund'' ( ar, جند; plural ''ajnad'', اجناد) was a military division, which became applied to Arab military colonies in the Muslim conquests, conquered lands and, most notably, to the provinces into which Bila ...
, a transcription factor, and
G9a Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the ''EHMT2'' gene. G9a catalyzes the mono- and di-methylated states of histone H3 at lysine residue 9 ...
, a histone methyltransferase, both oppose the function of ΔFosB and inhibit increases in its expression. Increases in nucleus accumbens ΔJunD expression (via viral vector-mediated gene transfer) or G9a expression (via pharmacological means) reduces, or with a large increase can even block, many of the neural and behavioral alterations that result from chronic high-dose use of addictive drugs (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Natural rewards, like drugs of abuse, induce gene expression of ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression.
Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers
Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well; in particular, ΔFosB in the nucleus accumbens is critical for the
reinforcing In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher freq ...
effects of sexual reward. Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess bidirectional cross-
sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of sti ...
effects that are mediated through ΔFosB. This phenomenon is notable since, in humans, a dopamine dysregulation syndrome, characterized by drug-induced compulsive engagement in natural rewards (specifically, sexual activity, shopping, and gambling), has also been observed in some individuals taking dopaminergic medications. ΔFosB inhibitors (drugs or treatments that oppose its action) may be an effective treatment for addiction and addictive disorders. The release of dopamine in the nucleus accumbens plays a role in the reinforcing qualities of many forms of stimuli, including naturally reinforcing stimuli like palatable food and sex. Altered dopamine
neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
is frequently observed following the development of an addictive state. In humans and lab animals that have developed an addiction, alterations in dopamine or
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
neurotransmission in the nucleus accumbens and other parts of the striatum are evident. Studies have found that use of certain drugs (e.g.,
cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...
) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.


Reward system


Mesocorticolimbic pathway

Understanding the pathways in which drugs act and how drugs can alter those pathways is key when examining the biological basis of drug addiction. The reward pathway, known as the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
, or its extension, the mesocorticolimbic pathway, is characterized by the interaction of several areas of the brain. * The projections from the ventral tegmental area (VTA) are a network of dopaminergic neurons with co-localized postsynaptic glutamate receptors (
AMPAR The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the centr ...
and
NMDAR The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...
). These cells respond when stimuli indicative of a reward are present. The VTA supports learning and sensitization development and releases DA into the
forebrain In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hindbrain (rhombencephalon) are the three primary ...
. These neurons also project and release DA into the nucleus accumbens, through the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
. Virtually all drugs causing drug addiction increase the dopamine release in the mesolimbic pathway, in addition to their specific effects. * The nucleus accumbens (NAcc) is one output of the VTA projections. The nucleus accumbens itself consists mainly of GABAergic medium spiny neurons (MSNs). The NAcc is associated with acquiring and eliciting conditioned behaviors, and is involved in the increased sensitivity to drugs as addiction progresses. Overexpression of ΔFosB in the nucleus accumbens is a necessary common factor in essentially all known forms of addiction; ΔFosB is a strong positive modulator of positively reinforced behaviors. * The
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
, including the anterior cingulate and orbitofrontal cortices, is another VTA output in the mesocorticolimbic pathway; it is important for the integration of information which helps determine whether a behavior will be elicited. It is also critical for forming associations between the rewarding experience of drug use and cues in the environment. Importantly, these cues are strong mediators of drug-seeking behavior and can trigger relapse even after months or years of abstinence. Other brain structures that are involved in addiction include: * The basolateral amygdala projects into the NAcc and is thought to also be important for motivation. * The
hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
is involved in drug addiction, because of its role in learning and memory. Much of this evidence stems from investigations showing that manipulating cells in the hippocampus alters dopamine levels in NAcc and firing rates of VTA dopaminergic cells.


Role of dopamine and glutamate

Dopamine is the primary neurotransmitter of the reward system in the brain. It plays a role in regulating movement, emotion, cognition, motivation, and feelings of pleasure. Natural rewards, like eating, as well as recreational drug use cause a release of dopamine, and are associated with the reinforcing nature of these stimuli. Nearly all addictive drugs, directly or indirectly, act upon the brain's reward system by heightening dopaminergic activity. Excessive intake of many types of addictive drugs results in repeated release of high amounts of dopamine, which in turn affects the reward pathway directly through heightened
dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
activation. Prolonged and abnormally high levels of dopamine in the
synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...
can induce receptor
downregulation In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
in the neural pathway. Downregulation of mesolimbic dopamine receptors can result in a decrease in the sensitivity to natural reinforcers. Drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the nucleus accumbens. This idea is supported with data from experiments showing that drug seeking behavior can be prevented following the inhibition of
AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...
glutamate receptors and glutamate release in the nucleus accumbens.


Reward sensitization

Reward sensitization is a process that causes an increase in the amount of reward (specifically, incentive salience) that is assigned by the brain to a rewarding stimulus (e.g., a drug). In simple terms, when reward sensitization to a specific stimulus (e.g., a drug) occurs, an individual's "wanting" or desire for the stimulus itself and its associated cues increases. Reward sensitization normally occurs following chronically high levels of exposure to the stimulus. ΔFosB (DeltaFosB) expression in D1-type medium spiny neurons in the nucleus accumbens has been shown to directly and positively regulate reward sensitization involving drugs and natural rewards. "Cue-induced wanting" or "cue-triggered wanting", a form of craving that occurs in addiction, is responsible for most of the compulsive behavior that people with addictions exhibit. During the development of an addiction, the repeated association of otherwise neutral and even non-rewarding
stimuli A stimulus is something that causes a physiological response. It may refer to: * Stimulation ** Stimulus (physiology), something external that influences an activity ** Stimulus (psychology), a concept in behaviorism and perception * Stimulus (eco ...
with drug consumption triggers an
associative learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machines; there is also evidence for some kind of l ...
process that causes these previously neutral stimuli to act as conditioned positive reinforcers of addictive drug use (i.e., these stimuli start to function as drug cues). As conditioned positive reinforcers of drug use, these previously neutral stimuli are assigned incentive salience (which manifests as a craving) – sometimes at pathologically high levels due to reward sensitization – which can transfer to the primary reinforcer (e.g., the use of an addictive drug) with which it was originally paired. Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess a bidirectional reward cross-sensitization effect that is mediated through ΔFosB. In contrast to ΔFosB's reward-sensitizing effect,
CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first de ...
transcriptional activity decreases user's sensitivity to the rewarding effects of the substance. CREB transcription in the nucleus accumbens is implicated in
psychological dependence Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
and symptoms involving a lack of pleasure or motivation during
drug withdrawal Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...
.


Neuroepigenetic mechanisms

Altered epigenetic regulation of gene expression within the brain's reward system plays a significant and complex role in the development of drug addiction. Addictive drugs are associated with three types of epigenetic modifications within neurons. These are (1) histone modifications, (2) epigenetic methylation of DNA at
CpG site The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...
s at (or adjacent to) particular genes, and (3) epigenetic downregulation or upregulation of
microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. mi ...
s which have particular target genes. As an example, while hundreds of genes in the cells of the nucleus accumbens (NAc) exhibit histone modifications following drug exposure – particularly, altered acetylation and methylation states of
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
residues – most other genes in the NAc cells do not show such changes.


Diagnosis


Classification


DSM-5

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term " substance use disorder" to refer to a spectrum of drug use-related disorders. The DSM-5 eliminates the terms " abuse" and "dependence" from diagnostic categories, instead using the specifiers of ''mild'', ''moderate'' and ''severe'' to indicate the extent of disordered use. These specifiers are determined by the number of diagnostic criteria present in a given case. In the DSM-5, the term ''drug addiction'' is synonymous with ''severe substance use disorder''. The DSM-5 introduced a new diagnostic category for behavioral addictions; however,
problem gambling Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to ''DSM-5'' if certain diagnostic criteria are met. Pathological gambling is ...
is the only condition included in that category in the fifth edition. Internet gaming disorder is listed as a "condition requiring further study" in the DSM-5. Past editions have used
physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
and the associated withdrawal syndrome to identify an addictive state.
Physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
occurs when the body has adjusted by incorporating the substance into its "normal" functioning – i.e., attains
homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
– and therefore physical withdrawal symptoms occur upon cessation of use. Tolerance is the process by which the body continually adapts to the substance and requires increasingly larger amounts to achieve the original effects. Withdrawal refers to physical and psychological symptoms experienced when reducing or discontinuing a substance that the body has become dependent on. Symptoms of withdrawal generally include but are not limited to body aches,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
, intense cravings for the substance,
dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and uneas ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, hallucinations, headaches, cold sweats, tremors, and seizures. During acute physical opioid withdrawal, symptoms of
restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
are common and may be profound. This phenomenon originated the colloquial term "kicking the habit". Medical researchers who actively study addiction have criticized the DSM classification of addiction for being flawed and involving arbitrary diagnostic criteria.


ICD-11

The eleventh revision of the
International Classification of Diseases The International Classification of Diseases (ICD) is a globally used diagnostic tool for epidemiology, health management and clinical purposes. The ICD is maintained by the World Health Organization (WHO), which is the directing and coordinating ...
, commonly referred to as
ICD-11 The ICD-11 is the eleventh revision of the International Classification of Diseases (ICD). It replaces the ICD-10 as the global standard for recording health information and causes of death. The ICD is developed and annually updated by the World H ...
, conceptualizes diagnosis somewhat differently. ICD-11 first distinguishes between problems with psychoactive substance use ("Disorders due to substance use") and behavioral addictions ("Disorders due to addictive behaviours"). With regard to psychoactive substances, ICD-11 explains that the included substances initially produce "pleasant or appealing psychoactive effects that are rewarding and reinforcing with repeated use, utwith continued use, many of the included substances have the capacity to produce dependence. They also have the potential to cause numerous forms of harm, both to mental and physical health." Instead of the DSM-5 approach of one diagnosis ("Substance Use Disorder") covering all types of problematic substance use, ICD-11 offers three diagnostic possibilities: 1) Episode of Harmful Psychoactive Substance Use, 2) Harmful Pattern of Psychoactive Substance Use, and 3) Substance Dependence.


Prevention


Abuse liability

Abuse liability, which is also known as addiction liability, is the tendency to use drugs in a non-medical situation. This is typically for euphoria, mood changing, or sedation. Abuse liability is used when the person using the drugs wants something that they otherwise can not obtain. The only way to obtain this is through the use of drugs. When looking at abuse liability there are a number of determining factors in whether the drug is abused. These factors are: the chemical makeup of the drug, the effects on the brain, and the age, vulnerability, and the health (mental and physical) of the population being studied. There are a few drugs with a specific chemical makeup that leads to a high abuse liability. These are: cocaine, heroin, inhalants, marijuana, MDMA (ecstasy), methamphetamine, PCP, synthetic cannabinoids, synthetic cathinones (bath salts), nicotine (e.g. tobacco), and alcohol.


Treatment and management

According to a review, "in order to be effective, all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation, such as cognitive behavioral therapy, individual and group psychotherapy, behavior modification strategies,
twelve-step program Twelve-step programs are international mutual aid programs supporting recovery from substance addictions, behavioral addictions and compulsions. Developed in the 1930s, the first twelve-step program, Alcoholics Anonymous (AA), aided its memb ...
s, and residential treatment facilities." A biosocial approach to the treatment of addiction brings to the fore the social determinants of illness and wellbeing and considers the dynamic and reciprocal relationships that exist for, and influence, the individual's experience. The work of A.V. Schlosser (2018) aims to pronounce the individual lived experiences of women receiving medication-assisted treatment (e.g., methadone, naltrexone, burprenorphine) in a long-term rehabilitation setting, through a twenty month long ethnographic fieldwork investigation. This person-centred research shows how the experiences of these women "emerge from stable systems of inequality based in intersectional gender, race, and class marginalization entangled with processes of intra-action." Viewing addiction treatment through this lens also highlights the importance of framing clients' own bodies as "social flesh." As Schlosser (2018) points out, "client bodies" as well as the "embodied experiences of self and social belonging emerge in and through the structures, temporalities, and expectations of the treatment centre." Further challenges and embodied tensions have the potential to arise as a result of the dynamics inherent in the patient-provider relationship, in addition to the experience of being "alienated from their own bodies, psyches and sociality's when sedated on medications in treatment." Biotechnologies currently make up a large portion of the future treatments for addiction. To name a few, deep-brain stimulation, agonist/antagonist implants and hapten conjugate vaccines. Vaccinations against addiction specifically overlaps with the belief that memory plays a large role in the damaging effects of addiction and relapses. Hapten conjugate vaccines are designed to block opioid receptors in one area, while allowing other receptors to behave normally. Essentially, once a high can no longer be achieved in relation to a traumatic event, the relation of drugs to a traumatic memory can be disconnected and therapy can then play a role in treatment.


Behavioral therapy

A meta-analytic review on the efficacy of various behavioral therapies for treating drug and behavioral addictions found that cognitive behavioral therapy (e.g., relapse prevention and
contingency management Contingency management (CM) is the application of the three-term contingency (or operant conditioning), which uses stimulus control and consequences to change behavior. CM originally derived from the science of applied behavior analysis (ABA), bu ...
),
motivational interviewing Motivational interviewing (MI) is a counseling approach developed in part by clinical psychologists William R. Miller and Stephen Rollnick. It is a directive, client-centered counseling style for eliciting behavior change by helping clients to e ...
, and a
community reinforcement approach Community reinforcement approach and family training (CRAFT) is a behavior therapy approach in psychotherapy for treating addiction developed by Robert J. Meyers in the late 1970s. Meyers worked with Nathan Azrin in the early 1970s whilst he was de ...
were effective interventions with moderate effect sizes. Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g.,
marathon running The marathon is a long-distance foot race with a distance of , usually run as a road race, but the distance can be covered on trail routes. The marathon can be completed by running or with a run/walk strategy. There are also wheelchair div ...
), actually prevents the development of certain drug addictions and is an effective adjunct treatment for drug addiction, and for psychostimulant addiction in particular. Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) reduces drug addiction risk, which appears to occur through the reversal of drug induced addiction-related neuroplasticity. One review noted that exercise may prevent the development of drug addiction by altering ΔFosB or
immunoreactivity An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoassay ...
in the striatum or other parts of the reward system. Aerobic exercise decreases drug self-administration, reduces the likelihood of relapse, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by addictions to several drug classes (decreased DRD2 density). Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.


Medication


Alcohol addiction

Alcohol, like opioids, can induce a severe state of
physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
and produce withdrawal symptoms such as delirium tremens. Because of this, treatment for alcohol addiction usually involves a combined approach dealing with dependence and addiction simultaneously. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal and are considered the gold standard of
alcohol detoxification Alcohol detoxification (also known as ''detox'') is the abrupt cessation of alcohol intake in individuals that have alcohol dependence. This process is often coupled with substitution of drugs that have effects similar to the effects of alcohol i ...
. Pharmacological treatments for alcohol addiction include drugs like
naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...
(opioid antagonist), disulfiram,
acamprosate Acamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol use disorder. For label updates seFDA index page for NDA 021431/ref> Acamprosate is thought to stabilize chemical signaling in the brai ...
, and topiramate. Rather than substituting for alcohol, these drugs are intended to affect the desire to drink, either by directly reducing cravings as with acamprosate and topiramate, or by producing unpleasant effects when alcohol is consumed, as with disulfiram. These drugs can be effective if treatment is maintained, but compliance can be an issue as alcoholic patients often forget to take their medication, or discontinue use because of excessive side effects. According to a
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
review, the opioid antagonist
naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...
has been shown to be an effective treatment for alcoholism, with the effects lasting three to twelve months after the end of treatment.


Behavioral addictions


Cannabinoid addiction

A 2013 review on cannabinoid addiction noted that the development of
CB1 receptor Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. The human CB1 receptor is expressed in the peripheral nervous system and centr ...
agonists that have reduced interaction with β-arrestin 2 signalling might be therapeutically useful., there has been some evidence of effective pharmacological interventions for cannabinoid addiction, however, none have been approved yet.


Nicotine addiction

Another area in which drug treatment has been widely used is in the treatment of
nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
addiction, which usually involves the use of
nicotine replacement therapy Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the ...
, nicotinic receptor antagonists, or nicotinic receptor partial agonists. Examples of drugs that act on nicotinic receptors and have been used for treating nicotine addiction include antagonists like bupropion and the partial agonist varenicline. A 2019 review looking at the partial agonist cytisine, names it an effective, and affordable cessation treatment for smokers. When access to varenicline and
nicotine replacement therapy Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the ...
is limited (due to availability or cost), cytisine is considered the first line of treatment for smoking cessation.


Opioid addiction

Opioids cause
physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
, and treatment typically addresses both dependence and addiction. Physical dependence is treated using replacement drugs such as
suboxone Buprenorphine/naloxone, sold under the brand name Suboxone among others, is a fixed-dose combination medication that includes buprenorphine and naloxone. It is used to treat opioid use disorder, and reduces the mortality of opioid use disorder ...
or subutex (both containing the active ingredients
buprenorphine Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...
) and
methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroi ...
. Although these drugs perpetuate physical dependence, the goal of opiate maintenance is to provide a measure of control over both pain and cravings. Use of replacement drugs increases the addicted individual's ability to function normally and eliminates the negative consequences of obtaining controlled substances illicitly. Once a prescribed dosage is stabilized, treatment enters maintenance or tapering phases. In the United States, opiate replacement therapy is tightly regulated in methadone clinics and under the DATA 2000 legislation. In some countries, other opioid derivatives such as
dihydrocodeine Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co-dydramol) or aspirin. It was developed in Germany in 1908 a ...
, dihydroetorphine and even heroin are used as substitute drugs for illegal street opiates, with different prescriptions being given depending on the needs of the individual patient.
Baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...
has led to successful reductions of cravings for stimulants, alcohol, and opioids, and also alleviates alcohol withdrawal syndrome. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy. Some studies show the interconnection between opioid
drug detoxification Drug detoxification (informally, detox) is variously the intervention in a case of physical dependence to a drug; the process and experience of a withdrawal syndrome; and any of various treatments for acute drug overdose. A detoxification program ...
and overdose mortality.


Psychostimulant addiction

, there is no effective
pharmacotherapy Pharmacotherapy is therapy using pharmaceutical drugs, as distinguished from therapy using surgery (surgical therapy), radiation (radiation therapy), movement (physical therapy), or other modes. Among physicians, sometimes the term ''medical ther ...
for any form of psychostimulant addiction. Reviews from 2015, 2016, and 2018 indicated that
TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
-
selective agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...
s have significant therapeutic potential as a treatment for psychostimulant addictions; however, , the only compounds which are known to function as TAAR1-selective agonists are
experimental drug An experimental drug is a medicinal product (a drug or vaccine) that has not yet received approval from governmental regulatory authorities for routine use in human or veterinary medicine. A medicinal product may be approved for use in one diseas ...
s.


Research

Research indicates that vaccines which utilize anti-drug monoclonal antibodies can mitigate drug-induced positive reinforcement by preventing the drug from moving across the blood–brain barrier; however, current vaccine-based therapies are only effective in a relatively small subset of individuals. , vaccine-based therapies are being tested in human clinical trials as a treatment for addiction and preventive measure against drug overdoses involving nicotine, cocaine, and methamphetamine. The new study shows, that the vaccine may also save lives during a drug overdose. In this instance, the idea is that the body will respond to the vaccine by quickly producing antibodies to prevent the opioids from accessing the brain. Since addiction involves abnormalities in glutamate and GABAergic neurotransmission, receptors associated with these neurotransmitters (e.g., AMPA receptors, NMDA receptors, and GABAB receptors) are potential therapeutic targets for addictions.
N-acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
, which affects
metabotropic glutamate receptor The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate re ...
s and NMDA receptors, has shown some benefit in preclinical and clinical studies involving addictions to cocaine, heroin, and cannabinoids. It may also be useful as an adjunct therapy for addictions to amphetamine-type stimulants, but more clinical research is required. Current medical reviews of research involving lab animals have identified a drug class – class I
histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are bei ...
s – that indirectly inhibits the function and further increases in the expression of accumbal ΔFosB by inducing
G9a Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the ''EHMT2'' gene. G9a catalyzes the mono- and di-methylated states of histone H3 at lysine residue 9 ...
expression in the nucleus accumbens after prolonged use. These reviews and subsequent preliminary evidence which used
oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...
or intraperitoneal administration of the sodium salt of butyric acid or other class I HDAC inhibitors for an extended period indicate that these drugs have efficacy in reducing addictive behavior in lab animals that have developed addictions to ethanol, psychostimulants (i.e., amphetamine and cocaine), nicotine, and opiates;Primary references involving sodium butyrate:


however, few clinical trials involving humans with addictions and any HDAC class I inhibitors have been conducted to test for treatment efficacy in humans or identify an optimal dosing regimen.
Gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
for addiction is an active area of research. One line of gene therapy research involves the use of viral vectors to increase the expression of
dopamine D2 receptor Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, in ...
proteins in the brain.


Epidemiology

Due to cultural variations, the proportion of individuals who develop a drug or behavioral addiction within a specified time period (i.e., the
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
) varies over time, by country, and across national population demographics (e.g., by age group, socioeconomic status, etc.).


Asia

The prevalence of alcohol dependence is not as high as is seen in other regions. In Asia, not only socioeconomic factors but also biological factors influence drinking behavior. The overall prevalence of smartphone ownership is 62%, ranging from 41% in China to 84% in South Korea. Moreover, participation in online gaming ranges from 11% in China to 39% in Japan. Hong Kong has the highest number of adolescents reporting daily or above Internet use (68%).
Internet addiction disorder Problematic internet use or pathological internet use is generally defined as problematic, compulsive use of the internet, that results in significant impairment in an individual's function in various life domains over a prolonged period of time. ...
is highest in the Philippines, according to both the IAT (Internet Addiction Test) – 5% and the CIAS-R (Revised Chen Internet Addiction Scale) – 21%.


Australia

The prevalence of substance use disorder among Australians was reported at 5.1% in 2009. The Australian Institute of Health and Welfare found that in 2019, 11% of people over 14 years old smoke daily. The AIHW also found that 9.9% of those who drink alcohol, 7.5% of the population 14 or older, may qualify as alcohol dependent.


Europe

In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8% for cannabis use, 0.77% for amphetamine use, 0.37% for opioid use, and 0.35% for cocaine use in 2017. The mortality rates for alcohol and illicit drugs were highest in Eastern Europe.


United States

Based upon representative samples of the US youth population in 2011, the lifetime prevalence of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively. Based upon representative samples of the US adult population in 2011, the 12 month prevalence of alcohol and illicit drug addictions were estimated at 12% and 2–3% respectively. The lifetime prevalence of prescription drug addictions is currently around 4.7%. about 22 million people in the United States need treatment for an addiction to alcohol, nicotine, or other drugs. Only about 10%, or a little over 2 million, receive any form of treatments, and those that do generally do not receive evidence-based care. One-third of
inpatient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health car ...
hospital costs and 20% of all deaths in the US every year are the result of untreated addictions and risky substance use. In spite of the massive overall economic cost to society, which is greater than the cost of
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
and all forms of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
combined, most doctors in the US lack the training to effectively address a drug addiction. Another review listed estimates of lifetime prevalence rates for several behavioral addictions in the United States, including 1–2% for compulsive gambling, 5% for sexual addiction, 2.8% for food addiction, and 5–6% for compulsive shopping. A systematic review indicated that the time-invariant prevalence rate for sexual addiction and related compulsive sexual behavior (e.g., compulsive masturbation with or without pornography, compulsive cybersex, etc.) within the United States ranges from 3–6% of the population. According to a 2017 poll conducted by the Pew Research Center, almost half of US adults know a family member or close friend who has struggled with a drug addiction at some point in their life. In 2019, opioid addiction was acknowledged as a national crisis in the United States. An article in ''
The Washington Post ''The Washington Post'' (also known as the ''Post'' and, informally, ''WaPo'') is an American daily newspaper published in Washington, D.C. It is the most widely circulated newspaper within the Washington metropolitan area and has a large nati ...
'' stated that "America's largest drug companies flooded the country with pain pills from 2006 through 2012, even when it became apparent that they were fueling addiction and overdoses." The National Epidemiologic Survey on Alcohol and Related Conditions found that from 2012 to 2013 the prevalence of
Cannabis use disorder Cannabis use disorder (CUD), also known as cannabis addiction or marijuana addiction, is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and ICD-10 as the continued use of cannabis despite clini ...
in U.S. adults was 2.9%.


Canada

A Statistics Canada Survey in 2012 found the lifetime prevalence and 12-month prevalence of substance use disorders were 21.6%, and 4.4% in those 15 and older. Alcohol abuse or dependence reported a lifetime prevalence of 18.1% and a 12-month prevalence of 3.2%. Cannabis abuse or dependence reported a lifetime prevalence of 6.8% and a 12-month prevalence of 3.2%. Other drug abuse or dependence has a lifetime prevalence of 4.0% and a 12-month prevalence of 0.7%. Substance use disorder is a term used interchangeably with a drug addiction. In
Ontario, Canada Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central C ...
between 2009 and 2017, outpatient visits for mental health and addiction increased from 52.6 to 57.2 per 100 people, emergency department visits increased from 13.5 to 19.7 per 1000 people and the number of hospitalizations increased from 4.5 to 5.5 per 1000 people. Prevalence of care needed increased the most amongst the 14-17 age group overall.


South America

The realities of opioid use and
opioid use disorder Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. O ...
in Latin America may be deceptive if observations are limited to epidemiological findings. In the
United Nations Office on Drugs and Crime The United Nations Office on Drugs and Crime (UNODC; French: ''Office des Nations unies contre la drogue et le crime'') is a United Nations office that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the ...
report, although South America produced 3% of the world's morphine and heroin and 0.01% of its opium, prevalence of use is uneven. According to the Inter-American Commission on Drug Abuse Control, consumption of heroin is low in most Latin American countries, although Colombia is the area's largest opium producer. Mexico, because of its border with the United States, has the highest incidence of use.


Addiction and the humanities


History and etymology

The
etymology Etymology ()The New Oxford Dictionary of English (1998) – p. 633 "Etymology /ˌɛtɪˈmɒlədʒi/ the study of the class in words and the way their meanings have changed throughout time". is the study of the history of the Phonological chan ...
of the term ''addiction'' throughout history has been often misunderstood and has taken on various meanings associated with the word. An example is the usage of the word in the religious landscape of early modern Europe. "Addiction" at the time meant "to attach" to something, giving it both positive and negative connotations. The object of this attachment could be characterized as "good or bad". However, the meaning of addiction during the early modern period was mostly associated with positivity and goodness; during this early modern and highly religious era of Christian revivalism and Pietistic tendencies, it was seen as a way of "devoting oneself to another". Modern research on addiction has led to a better understanding of the disease with research studies on the topic dating back to 1875, specifically on morphine addiction. This furthered the understanding of addiction being a medical condition. It wasn't until the 19th century that addiction was seen and acknowledged in the
Western world The Western world, also known as the West, primarily refers to the various nations and states in the regions of Europe, North America, and Oceania.
as a disease, being both a physical condition and mental illness. Today, addiction is understood both as a
biopsychosocial Biopsychosocial models are a class of trans-disciplinary models which look at the interconnection between biology, psychology, and socio-environmental factors. These models specifically examine how these aspects play a role in topics ranging from ...
and neurological disorder that negatively impacts those who are affected by it, most commonly associated with the use of drugs and excessive use of alcohol. The understanding of addiction has changed throughout history, which has impacted and continues to impact the ways it is medically treated and diagnosed.


The suffixes "-holic" and "-holism"

In contemporary modern English "-holic" is a suffix that can be added to a subject to denote an addiction to it. It was extracted from the word
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
(one of the first addictions to be widely identified both medically and socially) (correctly the root " wikt:alcohol" plus the suffix "-ism") by misdividing or rebracketing it into "alco" and "-holism". (Another such misdivision is interpreting "
helicopter A helicopter is a type of rotorcraft in which lift and thrust are supplied by horizontally spinning rotors. This allows the helicopter to take off and land vertically, to hover, and to fly forward, backward and laterally. These attributes ...
" as "heli-copter" rather than the etymologically correct "helico-pter", giving rise to such derived words as "
heliport A heliport is a small airport suitable for use by helicopters and some other vertical lift aircraft. Designated heliports typically contain one or more touchdown and liftoff areas and may also have limited facilities such as fuel or hangars. I ...
" and "jetcopter".) There are correct medico-legal terms for such addictions:
dipsomania Dipsomania is a historical term describing a medical condition involving an uncontrollable craving for alcohol or drugs. In the 19th century, the term dipsomania was used to refer to a variety of alcohol-related problems, most of which are known ...
is the medico-legal term for
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
; other examples are in this table:


Philosophy


Social scientific models


Biopsychosocial–spiritual

While regarded biomedically as a neuropsychological disorder, addiction is multi-layered, with biological, psychological,
social Social organisms, including human(s), live collectively in interacting populations. This interaction is considered social whether they are aware of it or not, and whether the exchange is voluntary or not. Etymology The word "social" derives from ...
, cultural and spiritual (biopsychosocial–spiritual) elements. A biopsychosocial–spiritual approach fosters the crossing of disciplinary boundaries, and promotes
holistic Holism () is the idea that various systems (e.g. physical, biological, social) should be viewed as wholes, not merely as a collection of parts. The term "holism" was coined by Jan Smuts in his 1926 book '' Holism and Evolution''."holism, n." OED On ...
considerations of addiction. A biopsychosocial–spiritual approach considers, for example, how physical environments influence experiences, habits, and patterns of addiction.
Ethnographic Ethnography (from Greek ''ethnos'' "folk, people, nation" and ''grapho'' "I write") is a branch of anthropology and the systematic study of individual cultures. Ethnography explores cultural phenomena from the point of view of the subject ...
engagements and developments in fields of knowledge have contributed to biopsychosocial–spiritual understandings of addiction, including the work of
Philippe Bourgois Philippe Bourgois (born 1956) is professor of anthropology and director of the Center for Social Medicine and Humanities in the Department of Psychiatry at the University of California at Los Angeles. He was the founding chair of the Department of ...
, whose fieldwork with street-level drug dealers in East Harlem highlights correlations between drug use and structural
oppression Oppression is malicious or unjust treatment or exercise of power, often under the guise of governmental authority or cultural opprobrium. Oppression may be overt or covert, depending on how it is practiced. Oppression refers to discrimination ...
in the United States. /sup> Prior models that have informed the prevailing biopsychosocial–spiritual consideration of addiction include:


Cultural model

The cultural model, an
anthropological Anthropology is the scientific study of humanity, concerned with human behavior, human biology, cultures, societies, and linguistics, in both the present and past, including past human species. Social anthropology studies patterns of behav ...
understanding of the emergence of drug use and abuse, was developed by Dwight Heath. Heath undertook
ethnographic Ethnography (from Greek ''ethnos'' "folk, people, nation" and ''grapho'' "I write") is a branch of anthropology and the systematic study of individual cultures. Ethnography explores cultural phenomena from the point of view of the subject ...
research and fieldwork with the Camba people of Bolivia from June 1956 to August 1957. Heath observed that adult members of society drank ‘large quantities of
rum Rum is a liquor made by fermenting and then distilling sugarcane molasses or sugarcane juice. The distillate, a clear liquid, is usually aged in oak barrels. Rum is produced in nearly every sugar-producing region of the world, such as the Ph ...
and became intoxicated for several contiguous days at least twice a month’. This frequent, heavy drinking from which intoxication followed was typically undertaken socially, during
festival A festival is an event ordinarily celebrated by a community and centering on some characteristic aspect or aspects of that community and its religion or cultures. It is often marked as a local or national holiday, mela, or eid. A festival ...
s. Having returned in 1989, Heath observed that whilst much had changed, ‘drinking parties’ remained, as per his initial observations, and ‘there appear to be no harmful consequences to anyone’. Heath's observations and interactions reflected that this form of social behaviour, the habitual heavy consumption of alcohol, was encouraged and valued, enforcing social bonds in the Camba community. Despite frequent intoxication, “even to the point of unconsciousness”, the Camba held no concept of
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
(a form of addiction), and no visible social problems associated with drunkenness, or addiction, were apparent. As noted by
Merrill Singer Merrill Singer (b. October 6, 1950 McKeesport, PA, USA) is a medical anthropologist and professor emeritus in Anthropology at The University of Connecticut and in Community Medicine at The University of Connecticut Health Center. He is best known ...
, Heath's findings, when considered alongside subsequent cross-cultural experiences, challenged the perception that intoxication is socially ‘inherently disruptive’. Following this fieldwork, Heath proposed the ‘cultural model’, suggesting that ‘problems’ associated with heavy drinking, such as alcoholism – a recognised form addiction – were cultural: that is, that
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
is determined by cultural beliefs, and therefore varies among cultures. Heath's findings challenged the notion that ‘continued use f alcoholis inexorably addictive and damaging to the consumer's health’. The cultural model did face criticism by Sociologist Robin Room and others, who felt anthropologists could “downgrade the severity of the problem”.
Merrill Singer Merrill Singer (b. October 6, 1950 McKeesport, PA, USA) is a medical anthropologist and professor emeritus in Anthropology at The University of Connecticut and in Community Medicine at The University of Connecticut Health Center. He is best known ...
found it notable that the ethnographers working within the prominence of the cultural model were part of the ‘wet generation’: while not blind to the ‘disruptive, dysfunctional and debilitating effects of alcohol consumption’, they were products ‘socialized to view alcohol consumption as normal’.


Subcultural model

Historically, addiction has been viewed from the etic perspective, defining users through the
pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
of their condition. As reports of drug use rapidly increased, the cultural model found application in anthropological
research Research is " creative and systematic work undertaken to increase the stock of knowledge". It involves the collection, organization and analysis of evidence to increase understanding of a topic, characterized by a particular attentiveness ...
exploring
western Western may refer to: Places *Western, Nebraska, a village in the US *Western, New York, a town in the US *Western Creek, Tasmania, a locality in Australia *Western Junction, Tasmania, a locality in Australia *Western world, countries that id ...
drug subculture practices. The approach evolved from the ethnographic exploration into the lived experiences and subjectivities of 1960s and
1970s File:1970s decade montage.jpg, Clockwise from top left: U.S. President Richard Nixon doing the V for Victory sign after his resignation from office following the Watergate scandal in 1974; The United States was still involved in the Vietnam War ...
drug subcultures. The seminal publication “Taking care of business”, by Edward Preble and John J. Casey, documented the daily lives of New York street-based intravenous heroin users in rich detail, providing unique insight into the dynamic social worlds and activities that surrounded their drug use. These findings challenge popular narratives of
immorality Immorality is the violation of moral laws, norms or standards. It refers to an agent doing or thinking something they know or believe to be wrong. Immorality is normally applied to people or actions, or in a broader sense, it can be applied to ...
and deviance, conceptualising substance abuse as a social
phenomenon A phenomenon ( : phenomena) is an observable event. The term came into its modern philosophical usage through Immanuel Kant, who contrasted it with the noumenon, which ''cannot'' be directly observed. Kant was heavily influenced by Gottfried ...
. Furthermore, it suggests that the prevailing culture can have a greater influence on drug taking behaviours than the physical and psychological effects of the drug itself. To marginalised individuals, drug subcultures can provide social connection, symbolic meaning, and socially constructed purpose that they may feel is unattainable through conventional means. The subcultural model demonstrates the complexities of addiction, highlighting the need for an integrated approach. It contends that a biosocial approach is required to achieve a
holistic Holism () is the idea that various systems (e.g. physical, biological, social) should be viewed as wholes, not merely as a collection of parts. The term "holism" was coined by Jan Smuts in his 1926 book '' Holism and Evolution''."holism, n." OED On ...
understanding of addiction.


Critical medical anthropology model

Emerging in the early
1980s File:1980s replacement montage02.PNG, 420px, From left, clockwise: The first Space Shuttle, ''Columbia'', lifts off in 1981; US president Ronald Reagan and Soviet leader Mikhail Gorbachev ease tensions between the two superpowers, leading to the ...
, the critical medical anthropology model was introduced, and as
Merrill Singer Merrill Singer (b. October 6, 1950 McKeesport, PA, USA) is a medical anthropologist and professor emeritus in Anthropology at The University of Connecticut and in Community Medicine at The University of Connecticut Health Center. He is best known ...
offers ‘was applied quickly to the analysis of drug use’. Where the cultural model of the
1950s The 1950s (pronounced nineteen-fifties; commonly abbreviated as the "Fifties" or the " '50s") (among other variants) was a decade that began on January 1, 1950, and ended on December 31, 1959. Throughout the decade, the world continued its re ...
looked at the social body, the critical medical anthropology model revealed the body politic, considering drug use and addiction within the context of macro level structures including larger political systems, economic inequalities, and the institutional power held over social processes. Highly relevant to addiction, the three issues emphasized in the model are: # The social production of suffering #
Self-medication Self-medication is a human behavior in which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions: for example headaches or fatigue. The substances most widely used in sel ...
# The political economy ( licit and illicit drugs) These three key points highlight how drugs may come to be used to self-medicate the psychological trauma of socio-political disparity and
injustice Injustice is a quality relating to unfairness or undeserved outcomes. The term may be applied in reference to a particular event or situation, or to a larger status quo. In Western philosophy and jurisprudence, injustice is very commonly—but n ...
, intertwining with licit and illicit drug market politics. Social suffering, “the misery among those on the weaker end of power relations in terms of physical health,
mental health Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental hea ...
and lived experience”, is used by anthropologists to analyse how individuals may have personal problems caused by political and economic power. From the perspective of critical medical anthropology heavy drug use and addiction is a consequence of such larger scale unequal distributions of power. The three models developed here – the cultural model, the subcultural model, and the Critical Medical Anthropology Model – display how addiction is not an experience to be considered only biomedically. Through consideration of addiction alongside the biological, psychological,
social Social organisms, including human(s), live collectively in interacting populations. This interaction is considered social whether they are aware of it or not, and whether the exchange is voluntary or not. Etymology The word "social" derives from ...
, cultural and spiritual (biopsychosocial–spiritual) elements which influence its experience, a holistic and comprehensive understanding can be built. Addiction causes an "astoundingly high financial and human toll" on individuals and society as a whole. In the United States, the total economic cost to society is greater than that of all types of diabetes and all cancers combined. These costs arise from the direct adverse effects of drugs and associated healthcare costs (e.g., emergency medical services and outpatient and inpatient care), long-term complications (e.g., lung cancer from smoking tobacco products,
liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
and
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
from chronic alcohol consumption, and
meth mouth Meth mouth is a colloquial term used to describe severe tooth decay and tooth loss, as well as tooth fracture, acid erosion, and other oral problems that are often symptomatic to extended use of the drug methamphetamine. The condition is though ...
from methamphetamine use), the loss of productivity and associated welfare costs, fatal and non-fatal accidents (e.g., traffic collisions), suicides, homicides, and incarceration, among others. In the United States, a study conducted by the National Institute on Drug Abuse has found that overdose deaths in the United States have almost tripled amongst male and females from 2002 to 2017, with 72,306 overdose deaths reported in 2017 in the U.S. 2020 marked the year with highest number of overdose deaths over a 12-month period, with 81,000 overdose deaths, exceeding the records set in 2017.


See also


Endnotes


Notes

; Image legend


References


Further reading

* *


External links

*
Why do our brains get addicted?
nbsp;– a
TEDMED TEDMED is an annual conference focusing on health and medicine, with a year-round web-based community. TEDMED is an independent event operating under license from the nonprofit TED (conference), TED conference. Background , TEDMED staff oper ...
2014 talk by Nora Volkow, the director of the National Institute on Drug Abuse at
NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
.
Kyoto Encyclopedia of Genes and Genomes KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis i ...
(KEGG) signal transduction pathways:
KEGG – human alcohol addiction

KEGG – human amphetamine addiction

KEGG – human cocaine addiction

– What are different types of Drug Addiction Treatment Programs
{{Authority control * Brain disorders Substance-related disorders