Addiction is a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences. Despite the involvement of a number of psychosocial factors, a biological process – one which is induced by repeated exposure to an addictive stimulus – is the core pathology that drives the development and maintenance of an addiction. The two properties that characterize all addictive stimuli are that they are reinforcing (i.e., they increase the likelihood that a person will seek repeated exposure to them) and intrinsically rewarding (i.e., they are perceived as being inherently positive, desirable, and pleasurable). Addiction is a disorder of the brain’s reward system which arises through transcriptional and epigenetic mechanisms and occurs over time from chronically high levels of exposure to an addictive stimulus.
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.
As described by two groups of researchers, addiction exacts an “astoundingly high financial and human toll” on individuals and society as a whole through the direct adverse effects of drugs, associated healthcare costs, long-term complications.
Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, and continued use despite consequences.Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).
Examples of drug and behavioral addictions include alcoholism, amphetamine addiction, cocaine addiction, nicotine addiction, opioid addiction, food addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 and the ICD-10 is gambling addiction. The term addiction is misused frequently to refer 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.
Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (i.e., internal vs external or environmental, respectively) that compete over the control of an individual’s elicited behaviors. Cognitive control, and particularly inhibitory control over behavior, is impaired in both addiction and attention deficit hyperactivity disorder. 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.
The term behavioral addiction correctly refers to a compulsion to engage in a natural reward – which is a behavior that is inherently rewarding (i.e., desirable or appealing) – despite adverse consequences. Preclinical evidence has demonstrated that marked increases in the expression of ΔFosB through repetitive and excessive exposure to a natural reward induces the same behavioral effects and neuroplasticity as occurs in a drug addiction
Reviews of preclinical studies indicate that long-term frequent and excessive consumption of high fat or sugar foods can produce an addiction (food addiction).
Gambling is a natural reward which is associated with compulsive behavior and for which clinical diagnostic manuals, namely the DSM-5, have identified diagnostic criteria for an “addiction”
Similarly, shopping and playing videogames are associated with compulsive behaviors in humans and have also been shown to activate the mesolimbic pathway and other parts of the reward system.
There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Roughly half of an individual’s risk for developing an addiction is derived from genetics, while the other half is derived from the environment.
In other words, anyone can become an addict under the right circumstances.
It has long been established that genetic factors along with environmental (e.g., psychosocial) factors are significant contributors to addiction vulnerability. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated by other studies.
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 could then change the structure or functioning of specific brain neurons during development. These altered brain neurons could change 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 genotype.
Genome-wide association studies (GWAS) are a recently developed research method which are used to examine genetic associations with dependence, addiction, and drug use. These studies employ an unbiased approach to finding genetic associations with specific phenotypes and give equal weight to all regions of DNA, including those with no ostensible relationship to drug metabolism or response. 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.
A study that highlights the significant role genetics play in addiction is the twin studies. Twins have similar and sometimes identical genetics. Analyzing these genes in relation to genetics has helped geneticists understand how much of a role genes play in addiction Adolescence represents a period of unique vulnerability for developing 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.
Statistics have shown that those who start to drink alcohol at a younger age are more likely to become dependent later on. About 33% of the population tasted their first alcohol between the ages of 15 and 17, while 18% experienced it prior to this. As for alcohol abuse or dependence, the numbers start off high with those who first drank before they were 12 and then drop off after that.
Individuals with comorbid (i.e., co-occurring) mental health disorders such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) or post-traumatic stress disorder are more likely to develop substance use disorders. The National Institute on Drug Abuse cites early aggressive behavior as a risk factor for substance use.
The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term “Substance Use Disorder” to refer to a spectrum of use-related conditions. 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. Specifiers are determined by the number of diagnostic criteria present in a given case. The manual has never actually used the term “addiction” clinically
Physical dependence occurs when the body has adjusted by incorporating the substance into its “normal” functioning – i.e., attains homeostasis – 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 anxiety, irritability, intense cravings for the substance, nausea, hallucinations, headaches, cold sweats, and tremors
Most recently, though, the NIH acknowledged advances in identifying biomarkers, noting they outperform traditional phenomenological categories in identifying types of psychosis. As a diagnostic biomarker, ΔFosB expression could be used to diagnose an addiction in humans, but this would require a brain biopsy and therefore is not used in clinical practice.
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 programs, and residential treatment facilities.”
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), motivational interviewing, and a community reinforcement approach were effective interventions with moderate effect sizes. Preclinical research using a rodent model of cue exposure therapy (CET) show that this type of treatment is more effective in adults compared to adolescents, however that adolescent outcomes can be improved by acute treatment at the time of (CET) with a dopamine 2 receptor agonist.
One review noted that exercise may prevent the development of drug addiction by altering ΔFosB or c-Fos immunoreactivity 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.
Alcohol, like opioids, can induce a severe state of physical dependence 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.
Pharmacological treatments for alcohol addiction include drugs like naltrexone (opioid antagonist), disulfiram, acamprosate, 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.
According to a Cochrane Collaboration review, the opioid antagonist naltrexone has been shown to be an effective treatment for alcoholism, with the effects lasting three to twelve months after the end of treatment
Behavioral addiction is a treatable condition. Treatment options include psychotherapy and psychopharmacotherapy (i.e., medications) or a combination of both. Cognitive behavioral therapy (CBT) is the most common form of psychotherapy used in treating behavioral addictions; it focuses on identifying patterns that trigger compulsive behavior and making lifestyle changes to promote healthier behaviors.
As of 2010, there are no effective pharmacological interventions for cannabinoid addiction. A 2013 review on cannabinoid addiction noted that the development of CB1 receptor agonists that have reduced interaction with β-arrestin 2 signaling might be therapeutically useful.
Another area in which drug treatment has been widely used is in the treatment of nicotine addiction, which usually involves the use of nicotine replacement therapy, 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.
Opioids cause physical dependence, and treatment typically addresses both dependence and addiction.
Physical dependence is treated using replacement drugs such as suboxone or subutex (both containing the active ingredients buprenorphine) and methadone. 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.
Baclofen 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.
As of May 2014, there is no effective pharmacotherapy for any form of psychostimulant addiction. Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.