Addiction

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"Addictive" redirects here. For other uses, see Addiction (disambiguation) and Addictive (disambiguation).
Addiction and dependence glossary[1][2][3]
• addiction – a state characterized by compulsive engagement in rewarding stimuli despite adverse consequences
• addictive behavior – a behavior that is both rewarding and reinforcing
• addictive drug – a drug that is both rewarding and reinforcing
• dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
• drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
• drug withdrawal – symptoms that occur upon cessation of repeated drug use
• physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
• psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached
• sensitization – an amplified response to a stimulus resulting from repeated exposure to it
• tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
(edit | history)

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences.[7] It can be thought of as a disease or biological process leading to such behaviors.[1][8] 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., something perceived as being positive or desirable).[1][3][6]

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 (e.g., morphine, cocaine, sexual intercourse, gambling, etc.).[1][9][10] ΔFosB, a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions;[9][10][11][12] two decades of research into ΔFosB's role in addiction have demonstrated that addiction arises, and addictive behavior intensifies or attenuates, along with the genetic overexpression of ΔFosB in the D1-type medium spiny neurons of the nucleus accumbens;[1][9][10][11] due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker.[1][9][11] ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.[note 1][1][9]

Addiction exacts a high toll on individuals and society as a whole through the direct adverse effects of drugs, associated healthcare costs, long-term complications (e.g., lung cancer with smoking tobacco, liver cirrhosis with drinking alcohol, or meth mouth from intravenous methamphetamine), the functional consequences of altered neural plasticity in the brain, and the consequent loss of productivity.[13][14] Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, and continued use despite consequences.[15] Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).[16]

Examples of drug and behavioral addictions include: alcoholism, amphetamine addiction, cocaine addiction, nicotine addiction, opiate addiction, exercise addiction, food addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 is gambling addiction. The term addiction is misused frequently to refer to other compulsive behaviors or disorders, particularly dependence, in news media.[17]

Behavioral addiction

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Main article: Behavioral 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.[5][10][12] Preclinical evidence has demonstrated that that overexpression of ΔFosB through repetitive and excessive performance of a natural reward induces the same behavioral effects and neuroplasticity as occurs in a drug addiction.[10][18][19]

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); moreover, reward cross-sensitization between amphetamine and sexual activity, a property in which exposure to one increases in the desire for both, has been shown to occur preclinically and clinically as a dopamine dysregulation syndrome;[10][18][19] ΔFosB expression is required for this cross-sensitization effect and it intensifies with the level of ΔFosB expression as well.[10][19]

Reviews of preclinical studies indicate that long-term frequent and excessive consumption of high fat or sugar foods can produce an addiction (food addiction or sugar addiction).[10][12] Exercise appears to be associated with an addictive state (exercise addiction),[10] but there is also significant preclinical and some clinical evidence that it prevents and can treat drug addictions, particularly those involving psychostimulants.[10][20][21]

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";[10] however, no research has been conducted to determine if the overexpression of ΔFosB (the 35–37 kD isoforms) is present in deceased gambling addicts to confirm that the DSM's diagnostic model correctly diagnoses an addiction instead of a compulsion. There is evidence from functional neuroimaging that gambling activates the reward system and the group of neurons where increases in ΔFosB gene expression occur in an addiction, the mesolimbic pathway.[10] Similarly, shopping and playing videogames are associated with compulsive behaviors in humans and have also been shown to activate the reward system and the mesolimbic pathway in particular.[10] Based upon this evidence, gambling addiction, video game addiction and shopping addiction are classified accordingly.[10]

Risk factors

Genetic factors

It has long been established that genetic factors along with social and psychological factors are contributors to addiction. A common theory along these lines is the self-medication hypothesis. 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.[22] 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.[22]

Overall, the data implicating specific genes in the development of drug addiction is mixed for most genes. One reason for this may be that the case is due to a focus of current research on common variants. Many addiction studies 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. On the other hand, the rare variant hypothesis states that genes with low frequencies in the population (<1%) confer much greater additional risk in the development of disease.[23]

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. This is not to say that previous findings, or the GWAS findings, are erroneous. The important effects of endophenotypes are typically not capable of being captured by these methods. Furthermore, genes identified in GWAS for drug addiction may be involved either in adjusting brain behavior prior to drug experiences, subsequent to them, or both. [24]

Mechanisms

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For gene-related vocabulary, see Glossary of gene expression terms; for addiction-related vocabulary, expand the glossary below.
Addiction and dependence glossary[1][2][3]
• addiction – a state characterized by compulsive engagement in rewarding stimuli despite adverse consequences
• addictive behavior – a behavior that is both rewarding and reinforcing
• addictive drug – a drug that is both rewarding and reinforcing
• dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
• drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
• drug withdrawal – symptoms that occur upon cessation of repeated drug use
• physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
• psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached
• sensitization – an amplified response to a stimulus resulting from repeated exposure to it
• tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
(edit | history)
Signaling cascade in the nucleus accumbens that results in psychostimulant addiction
v · t · e
The image above contains clickable links
This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamine and glutamate co-release by such psychostimulants,[25][26] postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation.[27][28][29] Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help of corepressors;[28] c-Fos repression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron.[30] A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated high-dose exposure to stimulants through this process.[31][32] ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.[31][32]

Current models of addiction from chronic addictive drug use involve alterations in gene expression in the mesocorticolimbic projection.[12][33][34] The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB).[12] ΔFosB is the most significant gene transcription factor in addiction since its viral or genetic overexpression in the nucleus accumbens is necessary and sufficient for most of the behaviors and neural adaptations seen in drug addiction.[12] 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 1][1][9] Specific drug addictions in which ΔFosB has been implicated in addictions to alcohol, amphetamine, cannabinoids, cocaine, methylphenidate, nicotine, phenylcyclidine, propofol, opiates, and substituted amphetamines, among others.[9][12][33][35][36] ΔJunD (a transcription factor) and G9a (an epigenetic enzyme) directly oppose ΔFosB's expression and function.[11][12] Increases in nucleus accumbens ΔJunD or G9a expression using viral vectors can reduce or, with a large increase, even block and reverse many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[11][12]

ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[12][37] 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.[10][12][37] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well;[12][10][37] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[37] 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.[10][19] 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.[10]

ΔFosB inhibitors (drugs or treatments that oppose its action) may be an effective treatment for addiction and addictive disorders.[38]

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.[39][40] Altered dopamine neurotransmission is frequently observed following the development of an addictive state.[10] 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.[10] Studies have found that use of certain drugs (e.g., cocaine) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.[41]

Summary of addiction-related plasticity

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This section is transcluded from FOSB. (edit | history)
Form of neural or behavioral plasticity Type of reinforcer Sources
Opiates Psychostimulants High fat or sugar food Sexual intercourse Physical exercise
(aerobic)		 Environmental
enrichment
ΔFosB expression in
nucleus accumbens D1-type MSNs		 ↑ ↑ ↑ ↑ ↑ ↑ [10]
Behavioral plasticity
Escalation of intake Yes Yes Yes [10]
Psychostimulant
cross-sensitization		 Yes Not applicable Yes Yes Attenuated Attenuated [10]
Psychostimulant
self-administration		 ↑ ↑ ↓ ↓ ↓ [10]
Psychostimulant
conditioned place preference		 ↑ ↑ ↓ ↑ ↓ ↑ [10]
Reinstatement of drug-seeking behavior ↑ ↑ ↓ ↓ [10]
Neurochemical plasticity
CREB phosphorylation
in the nucleus accumbens		 ↓ ↓ ↓ ↓ ↓ [10]
Sensitized dopamine response
in the nucleus accumbens		 No Yes No Yes [10]
Altered striatal dopamine signaling ↓DRD2, ↑DRD3 ↑DRD1, ↓DRD2, ↑DRD3 ↑DRD1, ↓DRD2, ↑DRD3 ↑DRD2 ↑DRD2 [10]
Altered striatal opioid signaling ↑μ-opioid receptors ↑μ-opioid receptors
↑κ-opioid receptors		 ↑μ-opioid receptors ↑μ-opioid receptors No change No change [10]
Changes in striatal opioid peptides ↑dynorphin ↑dynorphin ↓enkephalin ↑dynorphin ↑dynorphin [10]
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens ↓ ↑ ↑ [10]
Dendritic spine density in
the nucleus accumbens		 ↓ ↑ ↑ [10]

Reward system

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Main article: Reward system

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Mesocorticolimbic pathway

ΔFosB accumulation graph
Top: this depicts the acute expression of various Fos family proteins following an initial exposure to an addictive drug.
Bottom: this illustrates increasing ΔFosB expression from repeated twice daily drug binges, where these phosphorylated (35–37 kD) ΔFosB isoforms persist in mesolimbic dopamine neurons for up to 2 months.[42][32]

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, 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. The VTA supports learning and sensitization development and releases DA into the forebrain.[43] These neurons also project and release DA into the nucleus accumbens,[44] through the mesolimbic pathway. Virtually all drugs causing drug addiction increase the dopamine release in the mesolimbic pathway,[45] 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).[46] The NAcc is associated with acquiring and eliciting conditioned behaviors, and is involved in the increased sensitivity to drugs as addiction progresses.[43] Overexpression of ΔFosB in the nucleus accumbens is a necessary common factor in essentially all known forms of addiction;[1] ΔFosB is a strong positive modulator of positively reinforced behaviors.[1]
  • The prefrontal cortex, more specifically the anterior cingulate and orbitofrontal cortices,[47] is the other VTA output in the mesocorticolimbic pathway; it is important for the integration of information which helps determine whether a behavior will be elicited.[48]

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.[48]
  • 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 dopamine levels in NAcc and firing rates of VTA dopaminergic cells.[44]

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.[49] 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.[49][50] Nearly all addictive drugs, directly or indirectly, act upon the brain’s reward system by heightening dopaminergic activity.[51]

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.[49]

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.[47]

Reward sensitization

Neural and behavioral effects of validated ΔFosB transcriptional targets[9][52]
Target
gene		 Target
expression		 Neural effects Behavioral effects
c-Fos ↓ Molecular switch enabling the chronic
induction of ΔFosB[note 2]		 –
dynorphin ↓
[note 3]		  • Downregulation of κ-opioid feedback loop  • Increased drug reward
NF-κB ↑  • Expansion of NAcc dendritic processes
 • NF-κB inflammatory response in the NAcc
 • NF-κB inflammatory response in the CP
  • Increased drug reward
 • Increased drug reward
 • Locomotor sensitization
GluR2 ↑  • Decreased sensitivity to glutamate  • Increased drug reward
Cdk5 ↑  • GluR1 synaptic protein phosphorylation
 • Expansion of NAcc dendritic processes		 Decreased drug reward
(net effect)

Sensitization, or reverse tolerance, is the increase in response to a property of a stimulus (e.g., a drug) after repeated exposure. The protein ΔFosB (Delta-FosB) is known to positively regulate reward sensitization (i.e., higher levels of ΔFosB increases both drug reward and behavioral reward).[1][11] In simple terms, when reward sensitization to a specific stimulus (e.g., a drug) occurs, it increases an individual's positive perception of the stimulus, in turn promoting the desire to experience the stimulus again. In contrast to ΔFosB's reward-sensitizing effect, CREB transcriptional activity decreases user's sensitivity to the rewarding effects of the substance. CREB transcriptional activity in the nucleus accumbens is implicated in psychological dependence and the symptoms involving lack of pleasure or motivation during drug withdrawal. In an addiction, the intensity of addictive behavior following a relapse (i.e., patterns and levels of drug self-administration) does not noticeably attenuate (i.e., undergo psychological extinction) after several weeks of withdrawal due to the stability of certain ΔFosB isoforms which slowly accumulate during the development of an addiction (i.e., from frequent high-dose use of an addictive drug for an extended period); these isoforms remain activate in neurons for 1–2 months after drug use stops and are responsible for the persistence of these behaviors.[1][42][52]

The set of proteins known as "regulators of G protein signaling" (RGS) have been implicated in modulating some of the sensitization effects of opioid drugs.[53] RGS9-2 is an example of an RGS protein implicated in this effect.[53]

Diagnosis

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.[54] Currently, only drug addictions and gambling addiction are listed in the DSM-5. 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 upon cessation of use.[55] 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.

The director of the United States National Institute of Mental Health discussed the invalidity of the DSM-5's classification of mental disorders, writing:[56]

While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever.

The flawed and arbitrary nature of the DSM addiction classifications has also been criticized by medical researchers who actively study addiction pathophysiology.[57]

As a diagnostic biomarker, ΔFosB expression could be used to diagnose an addiction in humans, but this would require a brain biopsy and therefore isn't used in clinical practice.

Management

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See also: Addiction recovery groups, Cognitive behavioral therapy, and Drug rehabilitation

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Furthermore, 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.

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Medication

Lua error in package.lua at line 80: module 'strict' not found. As of May 2014, there is no effective pharmacotherapy for any form of psychostimulant addiction.[58][59][60][6] According to a Cochrane Collaboration review, the opioid antagonist naltrexone has short-term efficacy treating an alcohol dependence–withdrawal syndrome, but evidence of longer term efficacy is lacking.[61]

In addition to the traditional behavioral self-help groups and programs available for rehabilitation, there is a varied array of preventive and therapeutic approaches to combating addiction. For example, a common treatment option for opiate addiction is methadone maintenance. This process consists of administering the drug, a potent opiate with some potential for abuse, as a drink in a supervised clinical setting. In this way, the brain opiate levels increase slowly without producing the high but remain in the system long enough to deter addicts from injecting heroin.

Another form of drug therapy involves buprenorphine, a drug which seems to be even more promising than methadone.[62] A partial agonist for certain opiate receptors, this treatment blocks the effects of opiates but produces only mild reactions itself. Moreover, this method of detoxification has little value in the drug market.

New research indicates that it may even be possible to develop antibodies which combat a particular drug's effect on the brain, rendering the pleasurable effects null. Recently, vaccines have been developed against cocaine, heroin, methamphetamine, and nicotine. These advances are already being tested in human clinical trials and show serious promise as a preventive and recovery measure for addicts or those prone to addiction.[63][64]

Furthermore, another method of treatment for addiction that is being studied is deep brain stimulation. A serious procedure, DBS targets several brain regions including the nucleus accumbens, subthalamic nucleus, dorsal striatum, and medial prefrontal cortex among others.[65] Other studies have concurred and demonstrated that stimulation of the nucleus accumbens, an area that is apparently one of the most promising regions, allowed a seventy-year-old man to stop smoking without issue and attain a normal weight.[66]

Other forms of treatment include replacement drugs such as suboxone or subutex (both containing the active ingredient buprenorphine) and methadone; these are used as substitutes for illicit opiate drugs.[67][68] Although these drugs perpetuate physical dependence, the goal of opiate maintenance is to provide a clinically supervised, stable dose of a particular opioid in order to provide a measure of control to both pain and cravings. This provides a chance for the addict to function normally and to reduce the negative consequences associated with obtaining sufficient quantities of controlled substances illicitly, by both reducing opioid cravings and withdrawal symptomology. 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 levomethadyl acetate,[69] dihydrocodeine,[70] dihydroetorphine[71] and even heroin[72][73] are used as substitute drugs for illegal street opiates, with different drugs being used depending on the needs of the individual patient. Baclofen has been shown successful in attenuating cravings for most drugs of abuse – stimulants, ethanol, and opioids – and also attenuates the actual withdrawal syndrome of ethanol. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy.[74] It is possible that one of the best, albeit relatively unexplored, treatment modalities for opioid addiction – notoriously the most difficult addiction to treat (and to recover from), having relapse rates of around 23% at four weeks and 57% at twelve months if not on maintenance therapy with a mu-opioid agonist[74] – would be to combine an opioid maintenance agent, such as methadone or buprenorphine, to block withdrawal symptomology, with baclofen, to attenuate cravings and the desire to use, in people who find that they are still using or still craving drugs while on methadone or buprenorphine maintenance.

Other pharmacological treatments for alcohol addiction include drugs like naltrexone, disulfiram, acamprosate and topiramate,[75][76] but rather than substituting for alcohol, these drugs are intended to reduce 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.[77][78] Additional drugs acting on glutamate neurotransmission such as modafinil, lamotrigine, gabapentin and memantine have also been proposed for use in treating addiction to alcohol and other drugs.[79]

Another area in which drug treatment has been widely used is in the treatment of nicotine addiction. Various drugs have been used for this purpose such as bupropion, mecamylamine and the more recently developed varenicline. The cannaboinoid antagonist rimonabant has also been trialled for treatment of nicotine addiction but has not been widely adopted for this purpose.[80][81][82]

Ibogaine is a hallucinogen (psychotomimetic) that some claim interrupts addiction and reduces or eliminates withdrawal syndromes, specifically in regards to opioids.[83] Its mechanism of action is unknown, but likely linked to nAchR α3ß4 antagonism. In one animal trial, it was shown to slightly reduce self-administration of cocaine.[84] Another uncontrolled trial showed it reduced tremor by a mild to moderate degree during morphine withdrawal in rats.[85] These finding can not be extrapolated to human beings with any certainty. Research is complicated by the fact that ibogaine is illegal in many developed countries, and a Schedule I substance in the US, and as a result no controlled human trials have ever been performed. A semi-synthetic analogue of ibogaine, 18-methoxycoronaridine was developed, in an attempt to reduce the toxic (ibogaine is significantly cardiotoxic, and several deaths have been reported from its use; because of its illegal, underground nature, it is impossible to know how toxic the drug is) and psychotomimetic effects of the drug.

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) varies over time, by country, and across national population demographics (e.g., by age group, socioeconomic status, etc.).

Asia

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Australia

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Europe

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United States

Lua error in package.lua at line 80: module 'strict' not found. Based upon representative samples of the US youth population in 2011, the lifetime prevalence[note 4] of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively.[14] Based upon representative samples of US adult population in 2011, the 12 month prevalence of alcohol and illicit drug addictions were estimated at roughly 12% and 2–3% respectively.[14] The 12 month and lifetime prevalence of prescription drug addictions is currently unknown.

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.[10] 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.[18]

Personality theories of addiction

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. 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 model of impulsiveness and behavioral inhibition, and an impulsivity model of reward sensitization and impulsiveness.[86][90][91]

Notes

  1. ↑ 1.0 1.1 A decrease in aversion sensitivity, in simpler terms, essentially means that an individual is less likely to be concerned with undesirable outcomes.
  2. ↑ In other words, c-Fos repression allows ΔFosB to accumulate within nucleus accumbens dopamine neurons more rapidly because it is selectively induced in this state.[1]
  3. ↑ According to two medical reviews, ΔFosB has been implicated in causing both increases and decreases in dynorphin expression in different studies;[9][52] this table entry reflects only a decrease.
  4. ↑ The lifetime prevalence of an addiction is the percentage of individuals in a population (the one which the sample represents) that developed an addiction at some point in their life, at time of assessment.

Image legend

  1. ↑

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ 3.0 3.1 3.2 3.3 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 6.2 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ [1][3][4][5][6]
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 10.14 10.15 10.16 10.17 10.18 10.19 10.20 10.21 10.22 10.23 10.24 10.25 10.26 10.27 10.28 10.29 10.30 10.31 10.32 10.33 Lua error in package.lua at line 80: module 'strict' not found.Table 1"
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 12.11 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ 14.0 14.1 14.2 Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ 18.0 18.1 18.2 Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ 19.0 19.1 19.2 19.3 Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ 22.0 22.1 Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ 28.0 28.1 Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ 31.0 31.1 Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ 32.0 32.1 32.2 Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ 33.0 33.1 Lua error in package.lua at line 80: module 'strict' not found.
  34. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  35. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  36. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  37. ↑ 37.0 37.1 37.2 37.3 Lua error in package.lua at line 80: module 'strict' not found.
  38. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  39. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  40. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  41. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  42. ↑ 42.0 42.1 Lua error in package.lua at line 80: module 'strict' not found.
  43. ↑ 43.0 43.1 Lua error in package.lua at line 80: module 'strict' not found.
  44. ↑ 44.0 44.1 Lua error in package.lua at line 80: module 'strict' not found.
  45. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  46. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  47. ↑ 47.0 47.1 Lua error in package.lua at line 80: module 'strict' not found.
  48. ↑ 48.0 48.1 Lua error in package.lua at line 80: module 'strict' not found.
  49. ↑ 49.0 49.1 49.2 Lua error in package.lua at line 80: module 'strict' not found.
  50. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  51. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  52. ↑ 52.0 52.1 52.2 Lua error in package.lua at line 80: module 'strict' not found.
    Table 3
  53. ↑ 53.0 53.1 Lua error in package.lua at line 80: module 'strict' not found.
  54. ↑ http://www.dsm5.org/documents/substance%20use%20disorder%20fact%20sheet.pdf
  55. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  56. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  57. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  58. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  59. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  60. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  61. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  62. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  63. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  64. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  65. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  66. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  67. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  68. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  69. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  70. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  71. ↑ Lua error in package.lua at line 80: module 'strict' not found. Link
  72. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  73. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  74. ↑ 74.0 74.1 Lua error in package.lua at line 80: module 'strict' not found.
  75. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  76. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  77. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  78. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  79. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  80. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  81. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  82. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  83. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  84. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  85. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  86. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  87. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  88. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  89. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  90. ↑ [87][88][89]
  91. ↑ Lua error in package.lua at line 80: module 'strict' not found.

Further reading

  • Lua error in package.lua at line 80: module 'strict' not found.

External links

Kyoto Encyclopedia of Genes and Genomes signal transduction pathways:

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