Mechanisms
[edit]
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.[2][119][33] DeltaFosB (ΔFosB), a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions.[119][33][120][34] 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.[2][119][33][120] Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker.[2][119][120] ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.[note 2][2][119]
Chronic addictive drug use causes alterations in gene expression in the mesocorticolimbic projection.[34][128][129] The most important transcription factors that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NF-κB).[34] 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) seen in drug addiction.[34] ΔFosB expression in nucleus accumbens D1-type medium spiny neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion.[note 2][2][119] ΔFosB has been implicated in mediating addictions to many different drugs and drug classes, including alcohol, amphetamine and other substituted amphetamines, cannabinoids, cocaine, methylphenidate, nicotine, opiates, phenylcyclidine, and propofol, among others.[119][34][128][130][131] ΔJunD, a transcription factor, and G9a, a histone methyltransferase, both oppose the function of ΔFosB and inhibit increases in its expression.[2][34][132] 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).[120][34]
ΔFosB plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[34][133] 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.[33][34][133] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well;[34][33][133] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[133] 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 effects that are mediated through ΔFosB.[33][42][43] 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 been observed in some individuals taking dopaminergic medications.[33]
ΔFosB inhibitors (drugs or treatments that oppose its action) may be an effective treatment for addiction and addictive disorders.[134]
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.[135][136][32] Altered dopamine neurotransmission is frequently observed following the development of an addictive state.[33][26] In humans and lab animals that have developed an addiction, alterations in dopamine or opioid neurotransmission in the nucleus accumbens and other parts of the striatum are evident.[33] Use of certain drugs (e.g., cocaine) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.[137]
Reward system
[edit]
Main article: Reward system
Mesocorticolimbic pathway
[edit]
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,[26] 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 and NMDAR). These cells respond when stimuli indicative of a reward are present.[32] The VTA supports learning and sensitization development and releases dopamine (DA) into the forebrain.[139] These neurons project and release DA into the nucleus accumbens,[140] through the mesolimbic pathway. Virtually all drugs causing drug addiction increase the DA release in the mesolimbic pathway.[141][26]
The nucleus accumbens (NAcc) is one output of the VTA projections. The nucleus accumbens itself consists mainly of GABAergic medium spiny neurons (MSNs).[142] The NAcc is associated with acquiring and eliciting conditioned behaviors, and is involved in the increased sensitivity to drugs as addiction progresses.[139][31] Overexpression of ΔFosB in the nucleus accumbens is a necessary common factor in essentially all known forms of addiction;[2] ΔFosB is a strong positive modulator of positively reinforced behaviors.[2]
The prefrontal cortex, including the anterior cingulate and orbitofrontal cortices,[143][31] 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.[144] It is 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.[145][26]
Other brain structures that are involved in addiction include:
The basolateral amygdala projects into the NAcc and is thought to be important for motivation.[144]
The hippocampus 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 DA levels in NAcc and firing rates of VTA dopaminergic cells.[140]
Role of dopamine and glutamate
[edit]
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.[146] 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.[146][147][32] Nearly all addictive drugs, directly or indirectly, act on the brain's reward system by heightening dopaminergic activity.[148][26]
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 activation. Prolonged and abnormally high levels of dopamine in the synaptic cleft can induce receptor downregulation in the neural pathway. Downregulation of mesolimbic dopamine receptors can result in a decrease in the sensitivity to natural reinforcers.[146]
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 glutamate receptors and glutamate release in the nucleus accumbens.[143]
Reward sensitization
[edit]
Reward sensitization is a process that causes an increase in the amount of reward (specifically, incentive salience[note 5]) 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.[151][150][152] Reward sensitization normally occurs following chronically high levels of exposure to the stimulus.[26] ΔFosB 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.[2][119][120]
"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.[150][152] During the development of an addiction, the repeated association of otherwise neutral and even non-rewarding stimuli with drug consumption triggers an associative learning 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).[150][153][152] 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.[150][153][152]
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[note 6] that is mediated through ΔFosB.[33][42][43] In contrast to ΔFosB's reward-sensitizing effect, CREB transcriptional activity decreases user's sensitivity to the rewarding effects of the substance. CREB transcription in the nucleus accumbens is implicated in psychological dependence and symptoms involving a lack of pleasure or motivation during drug withdrawal.[2][138][149]
Neuroepigenetic mechanisms
[edit]
Further information: Neuroepigenetics and Chromatin remodeling
Altered epigenetic regulation of gene expression within the brain's reward system plays a significant and complex role in the development of drug addiction.[132][154] Addictive drugs are associated with three types of epigenetic modifications within neurons.[132] These are (1) histone modifications, (2) epigenetic methylation of DNA at CpG sites at (or adjacent to) particular genes, and (3) epigenetic downregulation or upregulation of microRNAs which have particular target genes.[132][34][154] 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 residues[154] – most other genes in the NAc cells do not show such changes.[132]
Diagnosis
[edit]
Further information: Substance use disorder § Diagnosis, and Problem gambling § Diagnosis
Classification
[edit]
DSM-5
[edit]
The fifth edition of the DSM 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.[18][24]
The DSM-5 introduced a new diagnostic category for behavioral addictions. Problem gambling is the only condition included in this category in the fifth edition.[20] Internet gaming disorder is listed as a "condition requiring further study" in the DSM-5.[155]
Past editions have used physical dependence and the associated withdrawal syndrome to identify an addictive state. 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 on cessation of use.[156] 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, irritability, intense cravings for the substance, dysphoria, nausea, hallucinations, headaches, cold sweats, tremors, and seizures. During acute physical opioid withdrawal, symptoms of restless legs syndrome are common and may be profound. This phenomenon originated the idiom "kicking the habit".
Medical researchers who actively study addiction have criticized the DSM classification of addiction for being flawed and involving arbitrary diagnostic criteria.[157]
ICD-11
[edit]
The eleventh revision of the International Classification of Diseases, commonly referred to as ICD-11, 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").[14] 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, [but] with continued use, many of the included substances have the capacity to produce dependence. They have the potential to cause numerous forms of harm, both to mental and physical health."[158] 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.[158]
Prevention
[edit]
Main articles: Harm reduction and Preventive healthcare
Abuse liability
[edit]
Abuse or addiction liability is the tendency to use drugs in a non-medical situation. This is typically for euphoria, mood changing, or sedation.[159] 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.[159] 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.[160]
Potential vaccines for addiction to substances
[edit]
Vaccines for addiction have been investigated as a possibility since the early 2000s.[161] The general theory of a vaccine intended to "immunize" against drug addiction or other substance abuse is that it would condition the immune system to attack and consume or otherwise disable the molecules of such substances that cause a reaction in the brain, thus preventing the addict from being able to realize the effect of the drug. Addictions that have been floated as targets for such treatment include nicotine, opioids, and fentanyl.[162][163][164][165] Vaccines have been identified as potentially being more effective than other anti-addiction treatments, due to "the long duration of action, the certainty of administration and a potential reduction of toxicity to important organs".[166]
Specific addiction vaccines in development include:
NicVAX, a conjugate vaccine intended to reduce or eliminate physical dependence on nicotine.[167] This proprietary vaccine is being developed by Nabi Biopharmaceuticals[168] of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten 3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa exotoxin A.[169]
TA-CD, an active vaccine[170] developed by the Xenova Group which is used to negate the effects of cocaine. It is created by combining norcocaine with inactivated cholera toxin. It works in much the same way as a regular vaccine. A large protein molecule attaches to cocaine, which stimulates response from antibodies, which destroy the molecule. This also prevents the cocaine from crossing the blood–brain barrier, negating the euphoric high and rewarding effect of cocaine caused from stimulation of dopamine release in the mesolimbic reward pathway. The vaccine does not affect the user's "desire" for cocaine—only the physical effects of the drug.[171]
TA-NIC, used to create human antibodies to destroy nicotine in the human body so that it is no longer effective.[172]
As of September 2023, it was further reported that a vaccine "has been tested against heroin and fentanyl and is on its way to being tested against oxycontin".[173]
Treatment and management
[edit]
See also: Addiction recovery groups, Cognitive behavioral therapy, and Drug rehabilitation
To be effective, treatment for addiction that is pharmacological or biologically based need to be accompanied by other interventions such as cognitive behavioral therapy (CBT), individual and group psychotherapy, behavior modification strategies, twelve-step programs, and residential treatment facilities.[174][28] The TTM can be used to determine when treatment can begin and which method will be most effective. If treatment begins too early, it can cause a person to become defensive and resistant to change.[82][175]
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.[176]
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-centered 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."[177] Viewing addiction treatment through this lens 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."[177]
Biotechnologies make up a large portion of the future treatments for addiction[178] including deep-brain stimulation, agonist and 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.[medical citation needed] 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 play a role in treatment.[179]
Behavioral therapy
[edit]
CBT proposes four assumptions essential to the approach to treatment: addiction is a learned behavior, it emerges in an environmental context, it is developed and maintained by particular thought patterns and processes, and CBT can be integrated well with other treatment and management approaches as they all have similar goals.[82] CBT, (e.g., relapse prevention), motivational interviewing, and a community reinforcement approach are effective interventions with moderate effect sizes.[180]
Interventions focusing on impulsivity and sensation seeking are successful in decreasing substance use.[31] Cue exposure uses ideas from classical conditioning theory to change the learned behavioral response of someone addicted to a cue or trigger. Contingency management uses ideas from operant conditioning to use meaningful positive reinforcements to influence addiction behaviors towards sobriety.[82]
Addiction recovery groups draw on different methods and models and rely on the success of vicarious learning, where people imitate behavior they observe as rewarding among their own social group or status as well as those perceived as being of a higher status.[82]
Substance addiction in children is complex and requires multifacted behavioral therapy. Family therapy and school-based interventions have had minor but lasting results. Innovative treatments are still needed for areas where relevant therapies are unavailable.[28]
Consistent aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of certain drug addictions and is an effective adjunct treatment for drug addiction, and for psychostimulant addiction in particular.[33][181][182][183][184] 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.[33][182] 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.[184] 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).[33][182] Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.[33][182][183]
With a combination of tools such as behavioral therapy, a balanced lifestyle, and individualized relapse plans, relapse is can be more successfully avoided.[82]
Medication
[edit]
Alcohol addiction
[edit]
Main article: Alcoholism
Further information: Alcohol and health and Long-term effects of alcohol
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. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal and are considered the gold standard of alcohol detoxification.[185]
Pharmacological treatments for alcohol addiction include drugs like naltrexone (opioid antagonist), disulfiram, acamprosate, and topiramate.[186][187] 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 patients with disordered alcohol use may forget to take their medication, or discontinue use because of excessive side effects.[188][189] 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.[190]
Behavioral addictions
[edit]
This section is transcluded from Behavioral addiction. (edit | history)
Behavioral addiction is a treatable condition.[191] 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. Because cognitive behavioral therapy is considered a short-term therapy, the number of sessions for treatment normally ranges from five to twenty.[192] During the session, therapists will lead patients through the topics of identifying the issue, becoming aware of one's thoughts surrounding the issue, identifying any negative or false thinking, and reshaping said negative and false thinking. While CBT does not cure behavioral addiction, it does help with coping with the condition in a healthy way. Currently, there are no medications approved for treatment of behavioral addictions in general, but some medications used for treatment of drug addiction may also be beneficial with specific behavioral addictions.[45]
Cannabinoid addiction
[edit]
Main article: Cannabis addiction
The development of CB1 receptor agonists that have reduced interaction with β-arrestin 2 signaling might be therapeutically useful.[193] As of 2019, there has been some evidence of effective pharmacological interventions for cannabinoid addiction, but none have been approved.[194]
Nicotine addiction
[edit]
Transdermal patch used in nicotine replacement therapy
Main article: Nicotine addiction
Further information: Smoking cessation and Tobacco harm reduction
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, and/or nicotinic receptor partial agonists.[195][196] 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.[195][196] Cytisine, a partial agonist, is an effective, and affordable cessation treatment for smokers.[197] When access to varenicline and nicotine replacement therapy is limited (due to availability or cost), cytisine is considered the first line of treatment for smoking cessation.[197]
Opioid addiction
[edit]
Main article: Opioid use disorder
Further information: Opioid epidemic
Opioids cause physical dependence and treatment typically addresses both dependence and addiction. Physical dependence is treated using replacement drugs such as buprenorphine (the active ingredient in products such as Suboxone and Subutex) and methadone.[198][199] 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,[200] dihydroetorphine[201] and even heroin[202][203] are used as substitute drugs for illegal street opiates, with different prescriptions being given depending on the needs of the individual patient. Baclofen has led to successful reductions of cravings for stimulants, alcohol, and opioids and alleviates alcohol withdrawal syndrome. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy.[204] Some studies show the interconnection between opioid drug detoxification and overdose mortality.[205]
Psychostimulant addiction
[edit]
There is no effective and FDA- or EMA-approved pharmacotherapy for any form of psychostimulant addiction.[206] Experimental TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions.[207]
Research
[edit]
Anti-drug vaccines (active immunizations) for treatment of cocaine and nicotine addictions were successful in animal studies. Vaccines tested on humans have been shown as safe with mild to moderate side effects, though did not have firm results confirming efficacy despite producing expected antibodies.[208] Vaccines which use anti-drug monoclonal antibodies (passive immunization) can mitigate drug-induced positive reinforcement by preventing the drug from moving across the blood–brain barrier.[209] Current[as of?] vaccine-based therapies are only effective in a relatively small subset of individuals.[209][210] As of November 2015, 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.[209] The study shows that the vaccine may 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.[211]
Since addiction involves abnormalities in glutamate and GABAergic neurotransmission,[212][213] receptors associated with these neurotransmitters (e.g., AMPA receptors, NMDA receptors, and GABAB receptors) are potential therapeutic targets for addictions.[212][213][214][215] N-acetylcysteine, which affects metabotropic glutamate receptors and NMDA receptors, has shown some benefit involving addictions to cocaine, heroin, and cannabinoids.[212] It may be useful as an adjunct therapy for addictions to amphetamine-type stimulants, but more clinical research is required.[212]
Current medical reviews of research involving lab animals have identified a drug class – class I histone deacetylase inhibitors[note 7] – that indirectly inhibits the function and further increases in the expression of accumbal ΔFosB by inducing G9a expression in the nucleus accumbens after prolonged use.[120][132][216][154] These reviews and subsequent preliminary evidence which used oral administration 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[note 8] that have developed addictions to ethanol, psychostimulants (i.e., amphetamine and cocaine), nicotine, and opiates.[132][154][217][218] 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.[note 9]
Gene therapy 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 proteins in the brain.[220][221][222][223][224]
Epidemiology
[edit]
Further information: Countries by alcohol consumption, Opioid epidemic, and Prevalence of tobacco use
Due to cultural variations, the proportion of individuals who develop a drug or behavioral addiction within a specified time period (i.e., the prevalence) varies over time, by country, and across national population demographics (e.g., by age group, socioeconomic status, etc.).[88] Where addiction is viewed as unacceptable, there will be fewer people addicted.
Asia
[edit]
The prevalence of alcohol dependence is not as high as is seen in other regions. In Asia, not only socioeconomic factors but biological factors influence drinking behavior.[225]
Internet addiction disorder is highest in the Philippines, according to both the IAT (Internet Addiction Test) – 5% and the CIAS-R (Revised Chen Internet Addiction Scale) – 21%.[226]
Australia
[edit]
Further information: Alcoholism in rural Australia
The prevalence of substance use disorder among Australians was reported at 5.1% in 2009.[227] In 2019 the Australian Institute of Health and Welfare conducted a national drug survey that quantified drug use for various types of drugs and demographics.[228] The national[specify] found that in 2019, 11% of people over 14 years old smoke daily; that 9.9% of those who drink alcohol, which equates to 7.5% of the total population age 14 or older, may qualify as alcohol dependent; that 17.5% of the 2.4 million people who used cannabis in the last year may have hazardous use or a dependence problem; and that 63.5% of about 300000 recent users of meth and amphetamines were at risk for developing problem use.[228]
Europe
[edit]
Further information: Alcoholism in Ireland and Alcoholism in Russia
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.[229] Data shows a downward trend of alcohol use among children 15 years old in most European countries between 2002 and 2014. First-time alcohol use before the age of 13 was recorded for 28% of European children in 2014.[28]
United States
[edit]
Further information: Cocaine in the United States, Crack epidemic in the United States, and Opioid epidemic in the United States
Based on representative samples of the US youth population in 2011, the lifetime prevalence[note 10] of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively.[230] Based on 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.[230] The lifetime prevalence of prescription drug addictions is around 4.7%.[231]
As of 2021, 43.7 million people aged 12 or older surveyed by the National Survey on Drug Use and Health in the United States needed treatment for an addiction to alcohol, nicotine, or other drugs. The groups with the highest number of people were 18–25 years (25.1%) and "American Indian or Alaska Native" (28.7%).[232] 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.[233][234] One-third of inpatient hospital costs and 20% of all deaths in the US every year are the result of untreated addictions and risky substance use.[233][234] In spite of the massive overall economic cost to society, which is greater than the cost of diabetes and all forms of cancer combined, most doctors in the US lack the training to effectively address a drug addiction.[233][234]
Estimates of lifetime prevalence rates in the US are 1–2% for compulsive gambling, 5% for sexual addiction, 2.8% for food addiction, and 5–6% for compulsive shopping.[33] 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 US ranges from 3–6% of the population.[41]
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.[235]
In 2019, opioid addiction was acknowledged as a national crisis in the United States.[236] An article in The Washington Post 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 in U.S. adults was 2.9%.[237]
Canada
[edit]
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.[238] Alcohol abuse or dependence reported a lifetime prevalence of 18.1% and a 12-month prevalence of 3.2%.[238] Cannabis abuse or dependence reported a lifetime prevalence of 6.8% and a 12-month prevalence of 3.2%.[238] Other drug abuse or dependence has a lifetime prevalence of 4.0% and a 12-month prevalence of 0.7%.[238] Substance use disorder is a term used interchangeably with a drug addiction.[239]
In Ontario, Canada 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.[240] Prevalence of care needed increased the most among the 14–17 age group overall.[240]
South America
[edit]
The realities of opioid use and opioid use disorder in Latin America may be deceptive if observations are limited to epidemiological findings. In the United Nations Office on Drugs and Crime report,[241] 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.[242]
Addiction and the humanities
[edit]
History and etymology
[edit]
Main article: Recreational drug use
Further information: Evolutionary models of human drug use, History of drinking, History of smoking, and Substance abuse in Ancient Rome
The etymology of the term addiction throughout history has been misunderstood and has taken on various meanings associated with the word.[243] An example is the usage of the word in the religious landscape of early modern Europe.[244] "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".[245] The meaning of addiction during the early modern period was mostly associated with positivity and goodness;[244] during this early modern and highly religious era of Christian revivalism and Pietistic tendencies,[244] it was seen as a way of "devoting oneself to another".[245]
Modern research on addiction has led to a better understanding of the disease with research on the topic dating back to 1875, specifically on morphine addiction.[246] This furthered the understanding of addiction being a medical condition. It was not until the 19th century that addiction was seen and acknowledged in the Western world as a disease, being both a physical condition and mental illness.[247] Today, addiction is understood both as a biopsychosocial 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.[3] 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"
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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 (one of the first addictions to be widely identified both medically and socially) (correctly the root "alcohol" plus the suffix "-ism") by misdividing or rebracketing it into "alco" and "-holism". There are correct medico-legal terms for such addictions: dipsomania is the medico-legal term for alcoholism;[248] other examples are in this table: