n.

嗜癖, 耽溺, 耽溺性, 習慣性, 中毒

関: addict、addictive、habit、habit-forming、habitual、habituation、intoxicate、intoxication、poisoning、toxicopathic、toxicosis

WordNet

(Roman law) a formal award by a magistrate of a thing or person to another person (as the award of a debtor to his creditor); a surrender to a master; "under Roman law addiction was the justification for slavery"
an abnormally strong craving
being abnormally tolerant to and dependent on something that is psychologically or physically habit-forming (especially alcohol or narcotic drugs) (同)dependence, dependance, dependency, habituation
put a habit on
the general form or mode of growth (especially of a plant or crystal); "a shrub of spreading habit"
attire that is typically worn by a horseback rider (especially a womans attire) (同)riding_habit
(psychology) an automatic pattern of behavior in reaction to a specific situation; may be inherited or acquired through frequent repetition; "owls have nocturnal habits"; "she had a habit twirling the ends of her hair"; "long use had hardened him to it" (同)use
a distinctive attire worn by a member of a religious order
an established custom; "it was their habit to dine at 7 every evening" (同)wont
someone who is so ardently devoted to something that it resembles an addiction; "a golf addict"; "a car nut"; "a bodybuilding freak"; "a news junkie" (同)nut, freak, junkie, junky
someone who is physiologically dependent on a substance; abrupt deprivation of the substance produces withdrawal symptoms
to cause (someone or oneself) to become dependent (on something, especially a narcotic drug) (同)hook
make drunk (with alcoholic drinks) (同)soak, inebriate
have an intoxicating effect on, of a drug
causing or characterized by addiction; "addictive drugs"; "addictive behavior" (同)habit-forming

PrepTutorEJDIC

(物事に)熱中すること《+『to』+『名』》 / (麻薬などの)常用《+『to』+『名』》
〈C〉 / 〈U〉〈C〉(個人の)『習慣』;(動・植物の)習性 / 〈C〉(麻薬などの)常用癖 / 〈C〉(僧衣など,特殊な)衣服
《受動態で用いて》(…に)〈人〉'を'熱中させる《+『名』〈人〉+『to』+『名』(do『ing』)》 / (麻薬などの)常用者,中毒者
(酒で)〈人〉‘を'『酔わせる』《+『名』+『with』(『from』)+『名』》 / 〈物事が〉〈人〉‘を'興奮させる,夢中にさせる
(薬品が)[麻薬]中毒を起こす,習慣性の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/28 20:32:37」(JST)

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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
• 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
• withdrawal – symptoms that occur after chronic use of a drug is reduced abruptly or stopped
(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]

1 Behavioral addiction
2 Risk factors
- 2.1 Genetic factors
3 Mechanisms
- 3.1 Summary of addiction-related plasticity
- 3.2 Reward system
  - 3.2.1 Mesocorticolimbic pathway
  - 3.2.2 Role of dopamine and glutamate
- 3.3 Reward sensitization
4 Diagnosis
5 Management
- 5.1 Medication
6 Epidemiology
- 6.1 Asia
- 6.2 Australia
- 6.3 Europe
- 6.4 United States
7 Personality theories of addiction
8 Notes
- 8.1 Image legend
9 References
10 Further reading
11 External links

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

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
• 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
• withdrawal – symptoms that occur after chronic use of a drug is reduced abruptly or stopped
(edit \| history)

Signaling cascade in the nucleus accumbens that results in psychostimulant addiction

Note: colored text contains article links.

Nuclear pore

Nuclear membrane

Plasma membrane

Ca_v1.2

NMDAR

AMPAR

DRD1

DRD5

DRD2

DRD3

DRD4

G_s

G_i/o

cAMP

PKA

CaM

CaMKII

DARPP-32

PP1

PP2B

CREB

ΔFosB

JunD

c-Fos

SIRT1

HDAC1

^{[Color legend 1]}

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 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

Form of neural or behavioral plasticity	Type of reinforcer						Sources
Form of neural or behavioral plasticity	Opiates	Psychostimulants	High fat or sugar food	Sexual intercourse	Physical exercise (aerobic)	Environmental enrichment	Sources
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

Mesocorticolimbic pathway

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

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.

“

”

Taylor SB, Lewis CR, Olive MF (2013). "The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans". Subst. Abuse Rehabil. 4: 29–43. doi:10.2147/SAR.S39684. PMC 3931688. PMID 24648786.

Medication

As of May 2014^[update], 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

Australia

Europe

United States

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

^ ^a ^b A decrease in aversion sensitivity, in simpler terms, essentially means that an individual is less likely to be concerned with undesirable outcomes.
^ 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]
^ 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.
^ 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

^

  Ion channel

  G proteins & linked receptors

  (Text color) Transcription factors

References

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compulsive eating, shopping, gambling, and sex–so-called “natural addictions”– Indeed, addiction to both drugs and behavioral rewards may arise from similar dysregulation of the mesolimbic dopamine system.
^ ^a ^b ^c Taylor SB, Lewis CR, Olive MF (February 2013). "The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans". Subst. Abuse Rehabil. 4: 29–43. doi:10.2147/SAR.S39684. PMC 3931688. PMID 24648786. Initial drug use can be attributed to the ability of the drug to act as a reward (ie, a pleasurable emotional state or positive reinforcer), which can lead to repeated drug use and dependence.8,9 A great deal of research has focused on the molecular and neuroanatomical mechanisms of the initial rewarding or reinforcing effect of drugs of abuse. ...
The tremendous need for more effective pharmacological treatments for psychostimulant addiction is a mainstay of contemporary addiction research. However, the recent downsizing of many major pharmaceutical companies away from psychiatric indications (including addiction) due to the lack of efficacy of experimental compounds in humans may require a sea change in the translational research approach.212,213 A new emphasis on larger-scale biomarker, genetic, and epigenetic research focused on the molecular targets of mental disorders has been recently advocated.212 In addition, the integration of cognitive and behavioral modification of circuit-wide neuroplasticity (ie, computer-based training to enhance executive function) may prove to be an effective adjunct-treatment approach for addiction, particularly when combined with cognitive enhancers.198,213–216 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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The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. ...

Conclusions
ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z ^aa ^ab ^ac ^ad ^ae ^af ^ag ^ah Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology 61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from “normal” to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)." Table 1"
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^ ^a ^b ^c Karila L, Wéry A, Weinstein A, Cottencin O, Petit A, Reynaud M, Billieux J (2014). "Sexual addiction or hypersexual disorder: different terms for the same problem? A review of the literature". Curr. Pharm. Des. 20 (25): 4012–4020. doi:10.2174/13816128113199990619. PMID 24001295. Sexual addiction, which is also known as hypersexual disorder, has largely been ignored by psychiatrists, even though the condition causes serious psychosocial problems for many people. A lack of empirical evidence on sexual addiction is the result of the disease's complete absence from versions of the Diagnostic and Statistical Manual of Mental Disorders. ... Existing prevalence rates of sexual addiction-related disorders range from 3% to 6%. Sexual addiction/hypersexual disorder is used as an umbrella construct to encompass various types of problematic behaviors, including excessive masturbation, cybersex, pornography use, sexual behavior with consenting adults, telephone sex, strip club visitation, and other behaviors. The adverse consequences of sexual addiction are similar to the consequences of other addictive disorders. Addictive, somatic and psychiatric disorders coexist with sexual addiction. In recent years, research on sexual addiction has proliferated, and screening instruments have increasingly been developed to diagnose or quantify sexual addiction disorders. In our systematic review of the existing measures, 22 questionnaires were identified. As with other behavioral addictions, the appropriate treatment of sexual addiction should combine pharmacological and psychological approaches.
^ ^a ^b ^c ^d Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". J. Neurosci. 33 (8): 3434–3442. doi:10.1523/JNEUROSCI.4881-12.2013. PMC 3865508. PMID 23426671. Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
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^ ^a ^b ^c "Dopamine in Drug Abuse and Addiction: Results of Imaging Studies and Treatment Implications".
^ "Drugs, Brains, and Behavior: The Science of Addiction".
^ "Understanding Drug Abuse and Addiction".
^ ^a ^b ^c Nestler EJ (October 2008). "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924. Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure—cited earlier (Renthal et al. in press). The mechanism responsible for ΔFosB repression of c-fos expression is complex and is covered below. ...
Examples of validated targets for ΔFosB in nucleus accumbens ... GluR2 ... dynorphin ... Cdk5 ... NFκB ... c-Fos
Table 3
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External links

Kyoto Encyclopedia of Genes and Genomes signal transduction pathways:

KEGG – human alcohol addiction
KEGG – human amphetamine addiction
KEGG – human cocaine addiction

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 処方剤の乱用および中毒：臨床的特徴、疫学、および寄与因子 prescription drug abuse and addiction clinical features epidemiology and contributing factors
2. オピオイドの乱用および依存の治療 treatment of opioid abuse and dependence
3. 処方剤の乱用および中毒：予防、同定、およびマネージメント prescription drug abuse and addiction prevention identification and management
4. アルコールおよびその他の薬物の有害な使用のスクリーニング screening for unhealthy use of alcohol and other drugs
5. 物質使用障害（SUD）：一般診療における認識と評価の原則 substance use disorders principles for recognition and assessment in general medical care

English Journal

The role of childhood trauma in bipolar disorders.

Aas M1,2,3, Henry C4,5,6,7,8, Andreassen OA9,10,11, Bellivier F12,13,14, Melle I15,16,17, Etain B18,19,20,21.
International journal of bipolar disorders.Int J Bipolar Disord.2016 Dec;4(1):2. doi: 10.1186/s40345-015-0042-0. Epub 2016 Jan 13.
This review will discuss the role of childhood trauma in bipolar disorders. Relevant studies were identified via Medline (PubMed) and PsycINFO databases published up to and including July 2015. This review contributes to a new understanding of the negative consequences of early life stress, as well
PMID 26763504

Informing alcohol interventions for student service members/veterans: Normative perceptions and coping strategies.

Miller MB1, Brett EI2, Leavens EL3, Meier E4, Borsari B5, Leffingwell TR6.
Addictive behaviors.Addict Behav.2016 Jun;57:76-82. doi: 10.1016/j.addbeh.2016.02.009. Epub 2016 Feb 9.
OBJECTIVE: The current study aimed to inform future interventions for heavy alcohol use and problems among college students by examining the utility of normative perceptions and coping strategies in predicting alcohol use among student service members/Veterans (SSM/Vs).METHODS: SSM/Vs and civilian s
PMID 26894552

Gambling transitions among adult gamblers: A multi-state model using a Markovian approach applied to the JEU cohort.

Bruneau M1, Grall-Bronnec M1, Vénisse JL1, Romo L2, Valleur M3, Magalon D4, Fatséas M5, Chéreau-Boudet I6, Luquiens A7; JEU-Group, Challet-Bouju G1, Hardouin JB8.
Addictive behaviors.Addict Behav.2016 Jun;57:13-20. doi: 10.1016/j.addbeh.2016.01.010. Epub 2016 Jan 22.
INTRODUCTION: The aim of this paper is to study transitions between two states of gambling in adulthood (problem gambling and non-problem gambling) and to identify factors that might influence these transitions.METHODS: Data for this 2-year long longitudinal study were collected in a French Outpatie
PMID 26827154

How to think about your drink: Action-identification and the relation between mindfulness and dyscontrolled drinking.

Schellhas L1, Ostafin BD2, Palfai TP3, de Jong PJ1.
Addictive behaviors.Addict Behav.2016 May;56:51-6. doi: 10.1016/j.addbeh.2016.01.007. Epub 2016 Jan 14.
Cross-sectional and intervention research have shown that mindfulness is inversely associated with difficulties in controlling alcohol use. However, little is known regarding the mechanisms through which mindfulness is related to increased control over drinking. One potential mechanism consists of t
PMID 26812278

Japanese Journal

＜研究ノート＞日本におけるギャンブル依存症患者に関する一考察 ― 依存症患者の脳機序に着目して ―

技術マネジメント研究 (16), 25-37, 2017-03-31
NAID 120006026932

計量調査から見る「ネット右翼」のプロファイル : 2007年／2014年ウェブ調査の分析結果をもとに

年報人間科学 38, 211-224, 2017-03-31
NAID 120005998754

横浜市中学生ネット依存調査

情報学研究・調査研究編 : 東京大学大学院情報学環 33, 159-219, 2017-03-30
NAID 120006221370

Social Networking Service (SNS) は境界性パーソナリティ障害の受け皿になりうるか？

健康科学 39, 65-70, 2017-03-24
NAID 120005981137

Related Pictures

★リンクテーブル★

リンク元	「麻薬中毒」「習慣性」「habitual」「habituation」「addictive」
拡張検索	「narcotic addiction」「cocaine addiction」「opiate addiction」「hospital addiction syndrome」