Substance dependence

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and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.

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that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.

974:, and use that persists even if the user is aware of severe adverse consequences. For some people, addiction becomes chronic, with periodic relapses even after long periods of abstinence. As a chronic, relapsing disease, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. While some with substance issues recover and lead fulfilling lives, others require ongoing additional support. The ultimate goal of addiction treatment is to enable an individual to manage their substance misuse; for some this may mean abstinence. Immediate goals are often to reduce substance abuse, improve the patient's ability to function, and minimize the medical and social complications of substance abuse and their addiction; this is called " 1923:ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. 1196:

and the needs of the addicted person, and also need to locate the defects of their ego and defense mechanisms. Using this approach alone has proven to be ineffective in solving addiction problems. Cognitive and behavioral techniques should be integrated with psychodynamic approaches to achieve effective treatment for substance related disorders. Cognitive treatment requires psychologists to think deeply about what is happening in the brain of an addicted person. Cognitive psychologists should zoom in to neural functions of the brain and understand that drugs have been manipulating the dopamine reward center of the brain. From this particular state of thinking, cognitive psychologists need to find ways to change the thought process of the addicted person.

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common mechanism of reward tolerance and dependence shared by several classes of drugs of abuse. Research since that time, by many laboratories, has provided substantial support for these hypotheses. Specifically, opiates in several CNS regions including NAc, and cocaine more selectively in NAc induce expression of certain adenylyl cyclase isoforms and PKA subunits via the transcription factor, CREB, and these transcriptional adaptations serve a homeostatic function to oppose drug action. In certain brain regions, such as locus coeruleus, these adaptations mediate aspects of physical opiate dependence and withdrawal, whereas in NAc they mediate reward tolerance and dependence that drives increased drug self-administration.

2041:; Henderson, A.S.; Strotzka, H.; Lipowski, Z.; Yu-cun, Shen; You-xin, Xu; Strömgren, E.; Glatzel, J.; Kühne, G.-E.; Misès, R.; Soldatos, C.R.; Pull, C.B.; Giel, R.; Jegede, R.; Malt, U.; Nadzharov, R.A.; Smulevitch, A.B.; Hagberg, B.; Perris, C.; Scharfetter, C.; Clare, A.; Cooper, J.E.; Corbett, J.A.; Griffith Edwards, J.; Gelder, M.; Goldberg, D.; Gossop, M.; Graham, P.; Kendell, R.E.; Marks, I.; Russell, G.; Rutter, M.; Shepherd, M.; West, D.J.; Wing, J.; Wing, L.; Neki, J.S.; Benson, F.; Cantwell, D.; Guze, S.; Helzer, J.; Holzman, P.; Kleinman, A.; Kupfer, D.J.; Mezzich, J.; Spitzer, R.; Lokar, J. 841:

observed to produce an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which is associated with blunted withdrawal in adult rats, but not neonatal rats While acute administration of opioids decreases AMPA receptor expression and depresses both NMDA and non-NMDA excitatory postsynaptic potentials in the NAC, withdrawal involves a lowered threshold for LTP and an increase in spontaneous firing in the NAc.

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patients. Most will have steps in place to handle severe withdrawal symptoms, either through behavioral therapy or other medications. Biological intervention should be combined with behavioral therapy approaches and other non-pharmacological techniques. Group therapies including anonymity, teamwork and sharing concerns of daily life among people who also have substance dependence issues can have a great impact on outcomes. However, these programs proved to be more effective and influential on persons who did not reach levels of serious dependence.

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legislations and agencies like the Federal Bureau of Narcotics (FBN) mid-20th century in response to the nation's growing substance abuse issue. These strict punishments for drug offenses shined light on the fact that drug abuse was a multi-faceted problem. The President's Advisory Commission on Narcotics and Drug Abuse of 1963 addressed the need for a medical solution to drug abuse. However, drug abuse continued to be enforced by the federal government through agencies such as the DEA and further legislations such as The

1847:, which occurs when drug taking stops. Dependence from long-term drug use may have both a somatic component, manifested by physical symptoms, and an emotional–motivation component, manifested by dysphoria. While physical dependence and withdrawal occur with some drugs of abuse (opiates, ethanol), these phenomena are not useful in the diagnosis of addiction because they do not occur with other drugs of abuse (cocaine, amphetamine) and can occur with many drugs that are not abused (propranolol, clonidine). 1292: 1002:. These kinds of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favorable outcomes than those in the US because the criteria for measuring success are functional rather than abstinence-based. The supporters of programs with total abstinence from drugs as a goal believe that enabling further drug use means prolonged drug use and risks an increase in addiction and complications from addiction. 5357: 1388:, and it was further hypothesized that this might potentially be able to cure opium addiction. However, many people did become addicted to morphine. In particular, addiction to opium became widespread among soldiers fighting in the Civil War, who very often required painkillers and thus were very often prescribed morphine. Women were also very frequently prescribed opiates, and opiates were advertised as being able to relieve "female troubles". 1117:– which is the gold standard for treatment of opioid dependence in developed countries, reducing the risk and cost to both user and society more effectively than any other treatment modality (for opioid dependence), and shows the best short-term and long-term gains for the user, with the greatest longevity, least risk of fatality, greatest quality of life, and lowest risk of relapse and legal issues including arrest and incarceration. 3678:| Living Hero Radio Show and Podcast special. With Dimitri Mobengo Mugianis, Bovenga Na Muduma, Clare S. Wilkins, Brad Burge, Tom Kingsley Brown, Susan Thesenga, Bruce K. Alexander, PhD ~ the voices of ex-addicts, researchers from The Multidisciplinary Association for Psychedelic Studies and Ibogaine/Iboga/Ayahuasca treatment providers sharing their experiences in breaking addiction with native medicines. January 2013 990:

dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments; shifting the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration; reduction in crime committed by drug addicts; and treatment of other comorbid conditions such as

1015:, an approach that looks at the relationship between thoughts, feelings and behaviors, addressing the root cause of maladaptive behavior. Cognitive-behavioral therapy treats addiction as a behavior rather than a disease, and so is subsequently curable, or rather, unlearnable. Cognitive-behavioral therapy programs recognize that, for some individuals, controlled use is a more realistic possibility. 1851:

phenomena. Second, the term substance dependence implies that dependence is the primary pharmacologic phenomenon underlying addiction, which is likely not true, as tolerance, sensitization, and learning and memory also play central roles. It is ironic and unfortunate that the Manual avoids use of the term addiction, which provides the best description of the clinical syndrome.

1410:(NSDUH) reports on substance dependence/abuse rates in various population demographics across the U.S. When surveying populations based on race and ethnicity in those ages 12 and older, it was observed that American Indian/Alaskan Natives were among the highest rates and Asians were among the lowest rates in comparison to other racial/ethnic groups. 2142:"Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (5th edition)2014 102 Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (5th edition) Washington, DC American Psychiatric Association 2013 xliv+947 pp. 9780890425541(hbck);9780890425558(pbck) £175 $ 199 (hbck); £45 $ 69 (pbck)". 1714:

In the past decade, there have been growing efforts through state and local legislations to shift from criminalizing drug abuse to treating it as a health condition requiring medical intervention. 28 states currently allow for the establishment of needle exchanges. Florida, Iowa, Missouri and Arizona

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Alcohol dependence or abuse rates were shown to have no correspondence with any person's education level when populations were surveyed in varying degrees of education from ages 26 and older. However, when it came to illicit drug use there was a correlation, in which those that graduated from college

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Internationally, the U.S. and Eastern Europe contain the countries with the highest substance abuse disorder occurrence (5-6%). Africa, Asia, and the Middle East contain countries with the lowest worldwide occurrence (1-2%). Across the globe, those that tended to have a higher prevalence of substance

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was isolated in the early 19th century, and came to be prescribed commonly by doctors, both as a painkiller and as an intended cure for opium addiction. At the time, the prevailing medical opinion was that the addiction process occurred in the stomach, and thus it was hypothesized that patients would

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to pair unpleasant effects with the thought of alcohol use. Psychologists tend to use an integration of all these approaches to produce reliable and effective treatment. With the advanced clinical use of medications, biological treatment is now considered to be one of the most efficient interventions

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strategies. In addition, the same author suggests that social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious. Community reinforcement has both efficacy and effectiveness data. In addition, behavioral treatment such as community reinforcement and family

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or other drugs despite problems related to use of the substance, substance dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance Abuse are considered Substance Use

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Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification

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Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to

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all introduced bills to allow for the establishment of needle exchanges in 2019. These bills have grown in popularity across party lines since needle exchanges were first introduced in Amsterdam in 1983. In addition, AB-186 Controlled substances: overdose prevention program was introduced to operate

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The United States' approach to substance abuse has shifted over the last decade, and is continuing to change. The federal government was minimally involved in the 19th century. The federal government transitioned from using taxation of drugs in the early 20th century to criminalizing drug abuse with

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under the control of licensing systems. Typically this legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession

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and group counseling. Frequently, a physician or psychiatrist will prescribe medications in order to help patients cope with the side effects of their addiction. Medications can help immensely with anxiety and insomnia, can treat underlying mental disorders (cf. self-medication hypothesis, Khantzian

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It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate,

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Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual: reliable supplies of a drug become difficult to secure, and the individual becomes vulnerable to both criminal abuse and legal punishment.

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Many soldiers in the Vietnam War were introduced to heroin and developed a dependency on the substance which survived even when they returned to the US. Technological advances in travel meant that this increased demand for heroin in the US could now be met. Furthermore, as technology advanced, more

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Treatments and attitudes toward addiction vary widely among different countries. In the US and developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug

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Medical professionals need to apply many techniques and approaches to help patients with substance related disorders. Using a psychodynamic approach is one of the techniques that psychologists use to solve addiction problems. In psychodynamic therapy, psychologists need to understand the conflicts

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for opioid detoxification, for first-time users or those who wish to attempt an abstinence-based recovery (90% of opioid users relapse to active addiction within eight months or are multiple relapse patients); or replacing an opioid that is interfering with or destructive to a user's life, such as

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Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use,

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In a survey of treatment providers from three separate institutions, the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors, measuring the treatment provider's responses on the "Spiritual Belief Scale" (a

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These findings led us to hypothesize that a concerted upregulation of the cAMP pathway is a general mechanism of opiate tolerance and dependence. ... We thus extended our hypothesis to suggest that, particularly within brain reward regions such as NAc, cAMP pathway upregulation represents a

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at the University of Chicago reported an analysis on disparities within admissions for substance abuse treatment in the Appalachian region, which comprises 13 states and 410 counties in the Eastern part of the U.S. While their findings for most demographic categories were similar to the national

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agonists into the locus coeruleus leads to a decrease in LC firing and norepinephrine release during withdrawal. A possible mechanism involves upregulation of NMDA receptors, which is supported by the attenuation of withdraw by NMDA receptor antagonists. Physical dependence on opioids has been

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Treatments for addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction, medical complications and the social needs of the individual. Determining the best type of recovery program for an addicted person depends on a number of factors,

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in the City and County of San Francisco. The bill was vetoed on September 30, 2018, by California Governor Jerry Brown. The legality of these sites are still in discussion, so there are no such sites in the United States yet. However, there is growing international evidence for successful safe

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in the context of opioid dependence. These approaches are aimed at the process of detoxification. Medical professionals weigh the consequences of withdrawal symptoms against the risk of staying dependent on these substances. These withdrawal symptoms can be very difficult and painful times for

756:. A sustained activation of CREB thus forces a larger dose to be taken to reach the same effect. In addition, it leaves the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for another dose. 1850:

The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2000), which makes distinctions between drug use, abuse, and substance dependence, is flawed. First, diagnosis of drug use versus abuse can be arbitrary and reflect cultural norms, not medical

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There are two routes typically applied to a cognitive approach to substance abuse: tracking the thoughts that pull patients to addiction and tracking the thoughts that prevent them if so from relapsing. Behavioral techniques have the widest application in treating substance related disorders.

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There is little evidence to confirm the safety or efficacy of most alternative therapies. Much of the information currently known about these therapies makes it clear that many have not been shown to be efficacious. Well-designed, stringently controlled research should be done to evaluate the

1683:. Even though the cost of producing most illegal addictive substances is very low, their illegality combined with the addict's need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. 2992:

Chambless, Dianne L.; Sanderson, William C.; Shoham, Varda; Johnson, Suzanne Bennett; Pope, Kenneth S.; Crits-Christoph, Paul; Baker, Mary; Johnson, Benjamin; Woody, Sheila R.; Sue, Stanley; Beutler, Larry; Williams, David A.; McCurry, Susan. "An Update on Empirically Validated Therapies".

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Many different ideas circulate regarding what is considered a successful outcome in the recovery from addiction. Programs that emphasize controlled drinking exist for alcohol addiction. Opiate replacement therapy has been a medical standard of treatment for opioid addiction for many years.

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findings by NSDUH, they had different results for racial/ethnic groups which varied by sub-regions. Overall, Whites were the demographic with the largest admission rate (83%), while Alaskan Native, American Indian, Pacific Islander, and Asian populations had the lowest admissions (1.8%).

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Another approach is to use medicines that interfere with the functions of the drugs in the brain. Similarly, one can also substitute the misused substance with a weaker, safer version to slowly taper the patient off of their dependence. Such is the case with

1365:, and dramatic increases in the recommendation of drug usage by clinical practitioners have exacerbated the problem significantly in the 20th century. Improved means of active biological agent manufacture and the introduction of synthetic compounds, such as 333:

Withdrawal is the body's reaction to abstaining from a substance upon which a person has developed a dependence syndrome. When dependence has developed, cessation of substance-use produces an unpleasant state, which promotes continued drug use through

154:. This was done because "the tolerance and withdrawal that previously defined dependence are actually very normal responses to prescribed medications that affect the central nervous system and do not necessarily indicate the presence of an addiction." 1010:

Residential drug treatment can be broadly divided into two camps: 12-step programs and therapeutic communities. 12-step programs are a nonclinical support-group and spiritual-based approach to treating addiction. Therapy typically involves the use of

1038:(rehab) centers offer a residential treatment program for some of the more seriously addicted, in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual 1212:. It uses the principle of pairing abused substances with unpleasant stimuli or conditions; for example, pairing pain, electrical shock, or nausea with alcohol consumption. The use of medications may also be used in this approach, such as using 1174:, are used by some practitioners to alleviate the symptoms of drug addiction. In 1997, the American Medical Association (AMA) adopted, as policy, the following statement after a report on a number of alternative therapies including acupuncture: 395:

compared the harm and dependence liability of 20 drugs, using a scale from zero to three for physical dependence, psychological dependence, and pleasure to create a mean score for dependence. Selected results can be seen in the chart below.

353:(NAS), which can have severe and life-threatening effects. Addiction to drugs such as alcohol in expectant mothers not only causes NAS, but also an array of other issues which can continually affect the infant throughout their lifetime. 1837:

Addictive drugs are both rewarding and reinforcing. ... Familiar pharmacologic terms such as tolerance, dependence, and sensitization are useful in describing some of the time-dependent processes that underlie addiction. ...

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to reduce cravings and propensity for relapse amongst addicts to any drug, especially effective in stimulant users, and alcoholics (in which it is nearly as effective as benzodiazepines in preventing complications); using

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When surveying populations based on gender in those ages 12 and older, it was observed that males had a higher substance dependence rate than females. However, the difference in the rates are not apparent until after age

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Dutcher, Linda W.; Anderson, Raymond; Moore, Marah; Luna-Anderson, Carol; Meyers, Robert J.; Delaney, Harold D.; Smith, Jane Ellen (2009). "Community Reinforcement and Family Training (CRAFT): An effectiveness study".

3622: 3602: 137:), substance dependence is redefined as a drug addiction, and can be diagnosed without the occurrence of a withdrawal syndrome. It was described accordingly: "When an individual persists in use of 4226: 2824:

Moggi F, Giovanoli A, Strik W, Moos BS, Moos RH (January 2007). "Substance use disorder treatment programs in Switzerland and the USA: Program characteristics and 1-year outcomes".

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training (CRAFT) have helped family members to get their loved ones into treatment. Motivational intervention has also shown to be an effective treatment for substance dependence.

771:. This activation influences the dysregulated emotional state associated with psychological dependence. They found that as drug use escalates, so does the presence of CRF in human 2344: 1675:

It is unclear whether laws against illegal drug use do anything to stem usage and dependency. In jurisdictions where addictive drugs are illegal, they are generally supplied by

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For the entirety of US history, drugs have been used by some members of the population. In the country's early years, most drug use by the settlers was of alcohol or tobacco.

188:– psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain 2789:

Reynolds M, Mezey G, Chapman M, Wheeler M, Drummond C, Baldacchino A (March 2005). "Co-morbid post-traumatic stress disorder in a substance misusing clinical population".

346:), or both. Chemical and hormonal imbalances may arise if the substance is not re-introduced. Psychological stress may also result if the substance is not re-introduced. 1548:

had the lowest rates. Furthermore, dependence rates were greater in unemployed populations ages 18 and older and in metropolitan-residing populations ages 12 and older.

2576:"Reflections on: "A general role for adaptations in G-Proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function"" 1655:, addictive drugs may be legal, legal only as part of a government sponsored study, illegal to use for any purpose, illegal to sell, or even illegal to merely possess. 3675: 109:

factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.

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1997) such as depression, and can help reduce or eliminate withdrawal symptomology when withdrawing from physiologically addictive drugs. Some examples are using

982:

including: personality, drugs of choice, concept of spirituality or religion, mental or physical illness, and local availability and affordability of programs.

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developed by the Xenova Group which is used to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining

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on smokers revealed that 80% of smokers quit for six months following the treatment, and 60% remained smoking free for 5 years following the treatment.

5115: 338:; i.e., the drug is used to escape or avoid re-entering the associated withdrawal state. The withdrawal state may include physical-somatic symptoms ( 3063:

Meyers, Robert J.; Smith, Jane Ellen; Lash, Denise N. (2005). "A program for engaging treatment-refusing substance abusers into treatment: CRAFT".

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meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.

3090:

Smith, Jane Ellen; Milford, Jaime L.; Meyers, Robert J. (2004). "CRA and CRAFT: Behavioral approaches to treating substance-abusing individuals".

759:

In addition to CREB, it is hypothesized that stress mechanisms play a role in dependence. Koob and Kreek have hypothesized that during drug use,

75:

because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of

1302: 2466:

AJ Giannini, RQ Quinones, DM Martin. Role of beta-endorphin and cAMP in addiction and mania. Society for Neuroscience Abstracts. 15:149, 1998.

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Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse".

1794: 309: 4423: 4293: 764: 1699:

serve to protect and promote public health by controlling the manufacturing, marketing, and distribution of products, like medications.

3458:, NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014. 2413: 925: 3243:

Martell BA, Mitchell E, Poling J, Gonsai K, Kosten TR (July 2005). "Vaccine pharmacotherapy for the treatment of cocaine dependence".

2336: 1774: 243:– dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome) 3716: 3480: 3455: 3396: 2705:"It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system" 619:

Capture rates enumerate the percentage of users who reported that they had become dependent to their respective drug at some point.

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Increased expression of AMPA receptors in nucleus accumbens MSNs is a potential mechanism of aversion produced by drug withdrawal.

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of the drug of study. Other studies in this review showed dysregulation of other neuropeptides that affect the HPA axis, including

776: 113: 3694: 3286: 1708: 4566: 2754:

Ball JC, van de Wijngaart GF (July 1994). "A Dutch addict's view of methadone maintenance--an American and a Dutch appraisal".

1407: 1150: 199:– an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) 4090: 3366: 3341: 1105:, with an opioid that can be administered legally, reduces or eliminates drug cravings, and does not produce a high, such as 1034:. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. 721: 71:, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a 2120: 361: 5381: 3470:"An Analysis of Mental Health and Substance Abuse Disparities & Access to Treatment Services in the Appalachian Region" 2180:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.).

1819:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.).

5308: 4780: 4637: 3729: 1121:

scale measuring belief in the four spiritual characteristics of AA identified by Ernest Kurtz); the scores were found to

5170: 4597: 4444: 3893: 3559: 1937:"Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms" 4146: 3117:

Motlagh, Farid Esmaeili; Ibrahim, Fatimah; Rashid, Rusdi Abd; Seghatoleslam, Tahereh; Habil, Hussain (5 April 2016).

2861: 2189: 1828: 1639: 1332: 386:

of a particular substance, route of administration, and time are critical factors for developing a drug dependence.

277:– a condition in which the use of substances leads to clinically and functionally significant impairment or distress 5233: 5100: 4199: 302: 2090: 1843:

is defined as an adaptive state that develops in response to repeated drug administration, and is unmasked during

5313: 5303: 4156: 4065: 4048: 3681: 1835:

The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. ...

1692: 1691:

In the United States, drug policy is primarily controlled by the federal government. The Department of Justice's

5335: 3670: 4550: 4205: 3799: 2877:

Giannini AJ (June 1996). "Alexithymia, affective disorders and substance abuse: possible cross-relationships".

2043:"The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines" 1035: 737: 713: 5386: 4936: 4377: 2965:

O'Donohue, William; Ferguson, Kyle E. (2006). "Evidence-based practice in psychology and behavior analysis".

2629:"The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal" 1141:

Behavioral programming is considered critical in helping those with addictions achieve abstinence. From the

5165: 5150: 5138: 5078: 4059: 4024: 1696: 1012: 350: 4697: 3312: 1129:

in the treatment provider's responses on the "Addiction Belief Scale" (a scale measuring adherence to the

4763: 4590: 4454: 4383: 4371: 4029: 3783: 834: 295: 5198: 4733: 4151: 3864: 3818: 3755: 1130: 1114: 261:– stimuli that the brain interprets as intrinsically positive and desirable or as something to approach 3695:"WHO Expert Committee on Drug Dependence – WHO Technical Report Series, No. 915 – Thirty-third Report" 5263: 5193: 5145: 5105: 4985: 4839: 4460: 4254: 2668:

Noda Y, Nabeshima T (October 2004). "Opiate physical dependence and N-methyl-D-aspartate receptors".

2051: 1745: 1716: 1704: 1314: 1142: 895: 717: 4615: 3021: 2999: 4946: 4019: 3983: 3917: 3901: 3854: 3827: 3641: 2442: 2337:"Supporting mothers with opioid addiction is the best bet in fighting neonatal abstinence syndrome" 939: 705: 343: 239: 1695:

enforces controlled substances laws and regulations. The Department of Health and Human Services'

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of a drug varies from substance to substance, and from individual to individual. Dose, frequency,

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Behavioral psychologists can use the techniques of "aversion therapy", based on the findings of

5268: 5088: 5055: 4980: 4975: 4768: 4525: 4486: 4317: 4215: 4095: 4035: 4014: 3973: 3962: 3906: 3809: 3774: 2994: 1209: 1158: 999: 918: 899: 335: 273: 1310: 5330: 5258: 5243: 5155: 4753: 4220: 4004: 3943: 3008: 1935:

Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012).

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Schaler JA (1997). "Addiction Beliefs of Treatment Providers: Factors Explaining Variance".

2409: 5253: 5110: 4798: 4775: 4717: 4692: 4476: 4249: 3989: 3721: 1126: 1023: 3456:

Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings

2042: 8: 5177: 5060: 5010: 5005: 4995: 4990: 4941: 4707: 4509: 4394: 4338: 4328: 4171: 4082: 3936: 3931: 3823: 3794: 3626: 3388: 1740: 1027: 1019: 955: 912: 859: 830: 818: 780: 772: 339: 285:– the diminishing effect of a drug resulting from repeated administration at a given dose 223: 86: 2436:"Dangerousness of Drugs A Guide To The Risks And Harms Associated With Substance Misuse" 2306: 211:– the escalating effect of a drug resulting from repeated administration at a given dose 5360: 5323: 5298: 5288: 5083: 5020: 5000: 4702: 4623: 4323: 4265: 4054: 3702: 3330: 3290: 3268: 3196: 3145: 3118: 2902: 2767: 2731: 2704: 2600: 2575: 2551: 2527:"Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis" 2526: 2502: 2477: 2391: 2276: 2251: 2223: 2206: 2014: 1989: 1961: 1936: 1909: 1884: 1861: 1859: 1779: 1659: 1392:

drugs were synthesized and discovered, opening up new avenues to substance dependency.

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has been implicated as the mechanism responsible for certain aspects of opioid-induced

792: 121: 106: 20: 2478:"Stress, dysregulation of drug reward pathways, and the transition to drug dependence" 2379: 833:. The temporal course of withdrawal correlates with LC firing, and administration of 5318: 5160: 4687: 4366: 3954: 3752: 3362: 3337: 3260: 3201: 3150: 2947: 2894: 2841: 2837: 2806: 2802: 2771: 2736: 2685: 2650: 2645: 2628: 2605: 2556: 2542: 2507: 2383: 2281: 2228: 2185: 2159: 2019: 2005: 1966: 1914: 1824: 1385: 877: 768: 725: 203: 72: 51: 3635: 3631: 3272: 2906: 1856: 4851: 4748: 4728: 4682: 4556: 4040: 3256: 3252: 3191: 3181: 3140: 3130: 3099: 3072: 3045: 2974: 2937: 2929: 2886: 2833: 2798: 2763: 2726: 2716: 2677: 2640: 2595: 2591: 2587: 2546: 2538: 2497: 2493: 2489: 2395: 2375: 2271: 2263: 2218: 2151: 2038: 2009: 2001: 1956: 1948: 1904: 1896: 1664: 1048: 383: 232: 1871: 966:

Addiction is a complex but treatable condition. It is characterized by compulsive

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The 19th century saw opium usage in the US become much more common and popular.

5208: 5036: 4740: 4677: 4431: 4121: 3877: 3418: 2068: 2056: 1735: 975: 788: 753: 653: 594: 499: 281: 252:– stimuli that increase the probability of repeating behaviors paired with them 177: 138: 81: 19:

This article is about drug and alcohol dependence. For alcohol dependence, see

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Nils Bejerot: Swedish addiction epidemic in an international perspective, 1988

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that psychologists may use as treatment for those with substance dependence.

1110: 1085: 1060: 1056: 945: 796: 729: 265: 256: 247: 189: 98: 94: 3615: 3611: 2155: 862:, evidence of tolerance or withdrawal, or without physiological dependence. 269:– an amplified response to a stimulus resulting from repeated exposure to it 4277: 3264: 3205: 3154: 2845: 2810: 2740: 2689: 2609: 2560: 2511: 2387: 2285: 2232: 2023: 1970: 1918: 1652: 1552:

Illicit Drug Dependence Demographics (Education, Employment, and Regional)

1362: 1149:

literature, several evidence based intervention programs have emerged: (1)

1075:, for withdrawal from barbiturates or benzodiazepines; using drugs such as 971: 967: 709: 480: 150:

and substance dependence were eliminated and replaced with the category of

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Most countries have legislation which brings various drugs and drug-like

1358: 1206: 1171: 556: 3594: 5293: 5133: 4970: 4604: 4161: 4115: 3560:"Bill Text - AB-186 Controlled substances: overdose prevention program" 1346: 1248: 1213: 1184: 1089: 1068: 1064: 1039: 891: 784: 391: 56: 3426: 2942: 4662: 4650: 4645: 4498: 3422: 3103: 3076: 3049: 2978: 1106: 1102: 1081: 1072: 995: 745: 184: 168: 16:

Need for a drug, whose discontinuation results in withdrawal symptoms

3507:"Drug Enforcement in the United States: History, Policy, and Trends" 3038:

Journal of Behavior Analysis in Health, Sports, Fitness and Medicine

1900: 4571: 4412: 4407: 4306: 4288: 4135: 3994: 2182:

Molecular Neuropharmacology: A Foundation for Clinical Neuroscience

2082: 1821:

Molecular Neuropharmacology: A Foundation for Clinical Neuroscience

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not become addicted to morphine if it was injected into them via a

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Mental health as a risk factor for illicit drug dependency or abuse

4830: 2252:"Neurobiologic Advances from the Brain Disease Model of Addiction" 1349:

of drug addiction has occurred to some degree throughout recorded

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The chemical muse: drug use and the roots of Western civilization

3116: 3034: 2184:(2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. 1823:(2nd ed.). New York: McGraw-Hill Medical. pp. 364–368. 1350: 1262: 1252: 1244: 683: 663: 461: 442: 3468:

Zhang Z, Infante A, Meit M, English N, Dunn M, Bowers K (2008).

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Pharmakon: Plato, Drug Culture, and Identity in Ancient Athens

2307:"Are addictions classified as being a mental health disorder?" 2037: 728:(NAcc) is one brain structure that has been implicated in the 85:, a distinct concept from substance dependence, is defined as 4902: 4897: 4887: 4882: 4877: 4871: 4864: 4857: 4825: 4810: 1354: 1266: 1240: 826: 704:

Two factors have been identified as playing pivotal roles in

176:

disorder characterized by persistent use of drugs (including

143: 89:, out-of-control drug use, despite negative consequences. An 3751: 3065:

International Journal of Behavioral Consultation and Therapy

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dependence were in their twenties, unemployed, and men. The

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practices, improvements in access to drugs, advancements in

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Substance Abuse and Mental Health Services Administration,

3242: 2991: 2788: 1990:"Natural rewards, neuroplasticity, and non-drug addictions" 991: 2365: 1981: 4845: 3389:"History of Drug Use and Drug Users in the United States" 2747: 2083:"Diagnostic criteria for Substance Dependence: DSM IV–TR" 219:– symptoms that occur upon cessation of repeated drug use 1885:"Transcriptional and epigenetic mechanisms of addiction" 775:. In rat models, the separate use of CRF inhibitors and 740:(cAMP) immediately after a high and triggers changes in 79:

and that necessitates the re-consumption of the drug. A

3660: 3535:"Needle exchanges find new champions among Republicans" 3467: 2823: 349:

Infants also experience substance withdrawal, known as

1934: 815: 760: 2964: 2175: 2173: 1497:

Substance Use in Different Genders w/ Respect to Age

1183:

In addition, new research surrounding the effects of

130:

Diagnostic and Statistical Manual of Mental Disorders

5096:

Community reinforcement approach and family training

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in the human body so that it is no longer effective.

795:, which enkephalin acts upon, is influential in the 752:

release into the NAcc by temporarily inhibiting the

2179: 1818: 1373:, are also factors contributing to drug addiction. 180:) despite substantial harm and adverse consequences 3329: 3089: 2412:. National Institute on Drug Abuse. January 2014. 2249: 2170: 3682:A social history of America's most popular drugs. 1807: 127:. Within the framework of the 4th edition of the 5373: 4289:Acute intoxication from hallucinogens (bad trip) 3305: 2250:Volkow ND, Koob GF, McLellan AT (January 2016). 3062: 2702: 227:– dependence that involves persistent physical– 3661:American Society of Addiction Medicine website 2524: 2469: 2198: 1882: 951:304.90 Other (or unknown) substance dependence 4631: 3737: 2667: 2243: 1299:The examples and perspective in this section 1269:but being used to create human anti-nicotine 303: 3417: 3236: 2852: 2567: 1795:Severity of Alcohol Dependence Questionnaire 4294:Hallucinogen persisting perception disorder 2913: 2441:. National Addiction Center. Archived from 1928: 1047:for alcohol detoxification, which prevents 767:(HPA axis) and other stress systems in the 699: 4638: 4624: 3744: 3730: 3287:"CelticPharma: TA-NIC Nicotine Dependence" 2204: 1317:, or create a new section, as appropriate. 854:"Substance dependence", as defined in the 791:that regulates pain. It also appears that 694: 310: 296: 3195: 3185: 3144: 3134: 2998: 2941: 2730: 2720: 2644: 2626: 2599: 2550: 2501: 2475: 2275: 2222: 2013: 1960: 1908: 1775:Alcohol Use Disorders Identification Test 1333:Learn how and when to remove this message 1136: 1051:and complications; using a slow taper of 3382: 3380: 3378: 3357:Rinella, Michael A. (23 November 2011). 3170:"Acupuncture therapy for drug addiction" 3119:"Acupuncture therapy for drug addiction" 2876: 2782: 2207:"Cellular basis of memory for addiction" 1165: 360: 114:International Classification of Diseases 4424:Kindling (sedative–hypnotic withdrawal) 3356: 3327: 2919: 2573: 1883:Robison AJ, Nestler EJ (October 2011). 1709:Comprehensive Crime Control Act of 1984 1190: 369: 231:withdrawal symptoms (e.g., fatigue and 5374: 4567:Chronic solvent-induced encephalopathy 3232:. New York, NY: Worth. pp. 1–589. 3167: 1876: 1414:Substance Use in Racial/Ethnic Groups 1408:National Survey on Drug Use and Health 1395: 1133:or the free-will model of addiction). 809: 4619: 4091:Alcohol-induced respiratory reactions 3725: 3504: 3450: 3448: 3446: 3444: 3442: 3440: 3375: 3227: 3223: 3221: 3219: 3217: 3215: 2817: 2347:from the original on 11 November 2017 2317:from the original on 11 November 2021 1987: 1693:Drug Enforcement Administration (DEA) 1220: 1199: 849: 722:cAMP response element binding protein 116:classifies substance dependence as a 3399:from the original on 7 December 2013 3168:Miller, Michael (24 February 2023). 1285: 1157:; (3) cue exposure therapy; and (4) 1022:, with prominent examples including 736:. In the NAcc, CREB is activated by 342:), emotional-motivational symptoms ( 5309:Discrimination against drug addicts 3688:NIDA for Teens: Brain and Addiction 3686:National Institute on Drug Abuse: " 799:and can regulate the expression of 765:hypothalamic–pituitary–adrenal axis 13: 5171:Tobacco cessation clinics in India 4598:Anabolic-androgenic steroids abuse 4227:Synthetic cannabinoid use disorder 3437: 3212: 2768:10.1111/j.1360-0443.1994.tb00974.x 2482:The American Journal of Psychiatry 2416:from the original on 17 April 2014 2211:Dialogues in Clinical Neuroscience 1697:Food and Drug Administration (FDA) 1179:efficacy of alternative therapies. 948:(or phencyclidine-like) dependence 14: 5398: 4147:Caffeine-induced anxiety disorder 3580: 3514:Federation of American Scientists 3386: 2762:(7): 799–802, discussion 803–14. 2294:of severe substance-use disorder. 2123:from the original on 13 June 2015 2093:from the original on 12 June 2015 1018:One of many recovery methods are 160:Addiction and dependence glossary 5356: 5355: 5234:Low-threshold treatment programs 5101:Motivational enhancement therapy 4200:Cannabinoid hyperemesis syndrome 2838:10.1016/j.drugalcdep.2006.05.017 2803:10.1016/j.drugalcdep.2004.08.017 2703:Chartoff EH, Connery HS (2014). 2670:European Journal of Pharmacology 2543:10.1016/j.neuropharm.2008.06.075 2476:Koob G, Kreek MJ (August 2007). 2006:10.1016/j.neuropharm.2011.03.010 1686: 1640:National Opinion Research Center 1290: 1155:community reinforcement approach 866:substance dependencies include: 614: 5314:Dopamine dysregulation syndrome 5304:Category:Vaccines against drugs 4157:Caffeine-induced sleep disorder 4049:Fetal alcohol spectrum disorder 3552: 3527: 3498: 3461: 3411: 3350: 3321: 3279: 3161: 3110: 3083: 3056: 3028: 2985: 2958: 2922:Addiction Research & Theory 2870: 2696: 2661: 2620: 2525:Carlezon WA, Thomas MJ (2009). 2518: 2460: 2428: 2402: 2359: 2329: 2299: 2256:New England Journal of Medicine 1705:Controlled Substances Act (CSA) 1400: 1170:Alternative therapies, such as 356: 4551:Sudden sniffing death syndrome 4206:Intravenous marijuana syndrome 3800:Post-acute-withdrawal syndrome 3257:10.1016/j.biopsych.2005.04.032 2592:10.1016/j.brainres.2015.12.039 2494:10.1176/appi.ajp.2007.05030503 2135: 2105: 2075: 2030: 1679:, who are often involved with 1646: 1059:, sometimes including another 1036:Substance-abuse rehabilitation 1005: 738:cyclic adenosine monophosphate 714:corticotropin-releasing factor 1: 4937:Adverse childhood experiences 4378:Opioid-induced endocrinopathy 2627:Rasmussen K (December 1995). 2380:10.1016/S0140-6736(07)60464-4 1941:Journal of Psychoactive Drugs 1801: 961: 744:that affect proteins such as 322: 5166:Nicotine replacement therapy 5151:Intensive outpatient program 5139:Residential treatment center 5079:Cognitive behavioral therapy 4591:Anabolic-androgenic steroids 4118:(alcohol use disorder (AUD)) 4060:Positional alcohol nystagmus 4025:Alcohol-related brain damage 3361:. Rowman & Littlefield. 2682:10.1016/j.ejphar.2004.07.017 2646:10.1016/0893-133X(95)00082-O 2205:Nestler EJ (December 2013). 1953:10.1080/02791072.2012.662112 1889:Nature Reviews. Neuroscience 1711:, and Anti-Drug Abuse Acts. 1013:cognitive-behavioral therapy 844: 748:; dynorphin peptides reduce 351:neonatal abstinence syndrome 7: 5382:Substance-related disorders 4764:Internet addiction disorder 4455:Benzodiazepine use disorder 4384:Opioid-induced constipation 4372:Opioid-induced hyperalgesia 4066:Wernicke–Korsakoff syndrome 4030:Alcohol withdrawal syndrome 3819:Substance-related disorders 3784:Substance-induced psychosis 3756:substance-related disorders 3328:Hillman DC (22 July 2008). 2891:10.2466/pr0.1996.78.3c.1389 2826:Drug and Alcohol Dependence 2791:Drug and Alcohol Dependence 2150:(3): 36–37. 11 March 2014. 1723: 1313:, discuss the issue on the 1234: 779:antagonists both decreased 23:. For substance abuse, see 10: 5403: 5199:List of twelve-step groups 4152:Caffeine-induced psychosis 4083:Respiratory tract diseases 4068:(WKS, Korsakoff psychosis) 3865:Combined drug intoxication 3564:leginfo.legislature.ca.gov 3505:Sacco L (2 October 2014). 3092:The Behavior Analyst Today 2967:The Behavior Analyst Today 2574:Nestler EJ (August 2016). 2059:. bluebook.doc. p. 65 1988:Olsen CM (December 2011). 1281: 1265:in development similar to 1151:behavioral marital therapy 1115:opioid replacement therapy 326: 18: 5351: 5281: 5264:Supervised injection site 5207: 5194:Addiction recovery groups 5186: 5146:Heroin-assisted treatment 5124: 5106:Motivational interviewing 5069: 5048: 5035: 4960: 4929: 4920: 4789: 4716: 4670: 4661: 4582: 4536: 4497: 4461:Benzodiazepine dependence 4445:Benzodiazepine withdrawal 4406: 4349: 4305: 4276: 4255:Prenatal cocaine exposure 4237: 4182: 4134: 4108: 4081: 4003: 3972: 3953: 3918:Gastrointestinal diseases 3916: 3892: 3885: 3876: 3842: 3762: 3588: 3187:10.1186/s13020-016-0088-7 3136:10.1186/s13020-016-0088-7 2934:10.3109/16066359709002970 2709:Frontiers in Pharmacology 2052:World Health Organization 1746:Risk factors in pregnancy 1143:applied behavior analysis 1020:12-step recovery programs 896:benzodiazepine dependence 718:gene transcription factor 291: 164: 159: 50: 42: 37: 4947:Psychological dependence 4781:Digital media addictions 4020:Alcoholic polyneuropathy 3984:Alcohol-related dementia 3902:Alcoholic cardiomyopathy 3855:Polysubstance dependence 3828:Psychological dependence 3666:Health-EU Portal – Drugs 3314:Drug Addiction Treatment 2722:10.3389/fphar.2014.00116 1867:MedlinePlus Encyclopedia 940:Polysubstance dependence 860:physiological dependence 858:, can be diagnosed with 706:psychological dependence 700:Psychological dependence 411:Psychological dependence 344:psychological dependence 240:psychological dependence 93:is a drug which is both 5249:Needle exchange program 5239:Managed alcohol program 5217:Category:Harm reduction 4440:Benzodiazepine overdose 4072:Wernicke encephalopathy 3926:Alcoholic liver disease 3894:Cardiovascular diseases 2633:Neuropsychopharmacology 2156:10.1108/rr-10-2013-0256 1790:Paddington Alcohol Test 1273:in a person to destroy 1000:mental health disorders 787:which is an endogenous 695:Biomolecular mechanisms 152:substance use disorders 5269:Tobacco harm reduction 5089:Contingency management 5056:Alcohol detoxification 4769:Internet sex addiction 4526:Amphetamine dependence 4487:Barbiturate dependence 4318:Green Tobacco Sickness 4216:Amotivational syndrome 4096:Alcoholic lung disease 4036:Alcoholic hallucinosis 4015:Alcoholic hallucinosis 3963:Alcoholic ketoacidosis 3907:Alcohol flush reaction 3775:Substance intoxication 3701:. 2003. Archived from 3676:Trips Beyond Addiction 3016:Cite journal requires 2410:"Marijuana Drug Facts" 2113:"Substance Dependence" 1872:Substance use disorder 1720:injection facilities. 1422:Dependence/Abuse Rate 1210:classical conditioning 1181: 1159:contingency management 1137:Behavioral programming 919:Amphetamine dependence 900:barbiturate dependence 894:dependence (including 366: 336:negative reinforcement 274:substance use disorder 73:psychoactive substance 5331:Motivational salience 5259:Stimulant maintenance 5244:Moderation Management 5156:Methadone maintenance 4221:Cannabis use disorder 3944:Auto-brewery syndrome 2879:Psychological Reports 2313:. 16 September 2020. 2268:10.1056/NEJMra1511480 1785:CRAFFT Screening Test 1756:Stimulant maintenance 1731:Addictive personality 1176: 1166:Alternative therapies 1147:behavioral psychology 921:(or amphetamine-like) 364: 5387:Substance dependence 5254:Responsible drug use 5111:Motivational therapy 4776:Video game addiction 4477:Barbiturate overdose 4250:Cocaine intoxication 3990:Alcohol intoxication 3832:Substance dependence 3671:people, drug addicts 2864:22 June 2007 at the 1717:safe injection sites 1311:improve this section 1301:may not represent a 1191:Treatment and issues 1024:Alcoholics Anonymous 814:Upregulation of the 414:Physical dependence 380:dependence liability 376:dependence potential 370:Dependence potential 146:(released in 2013), 65:Substance dependence 38:Substance dependence 5178:Twelve-step program 5061:Drug detoxification 4942:Physical dependence 4510:Stimulant psychosis 4395:Opioid use disorder 4339:Nicotine dependence 4329:Nicotine withdrawal 4172:Caffeine dependence 3932:Alcoholic hepatitis 3824:Physical dependence 3795:Neonatal withdrawal 3393:www.druglibrary.org 3230:Abnormal Psychology 2885:(3 Pt 2): 1389–90. 2537:(Suppl 1): 122–32. 1741:Physical dependence 1609:small metropolitan 1597:no-degree, college 1589:large metropolitan 1553: 1498: 1415: 1396:Society and culture 1145:literature and the 1093:illicitly-obtained 1028:Narcotics Anonymous 956:Nicotine dependence 913:Cannabis dependence 831:physical dependence 819:signal transduction 810:Physical dependence 781:self-administration 773:cerebrospinal fluid 340:physical dependence 224:physical dependence 142:Disorders." In the 5336:Incentive salience 5324:Inhibitory control 5299:Category:Addiction 5289:Addiction medicine 5084:Relapse prevention 5021:Tanning dependence 4324:Nicotine poisoning 4266:Cocaine dependence 4195:Cannabis arteritis 4055:Korsakoff syndrome 3955:Endocrine diseases 3293:on 6 December 2009 1780:CAGE questionnaire 1563:Employment status 1551: 1496: 1413: 1221:Medicinal approach 1200:Cognitive approach 907:Cocaine dependence 872:Alcohol dependence 850:DSM classification 793:μ-opioid receptors 367: 204:drug sensitization 107:gene transcription 21:Alcohol dependence 5369: 5368: 5319:Cognitive control 5277: 5276: 5161:Smoking cessation 5116:Physical exercise 5031: 5030: 5017:Non-drug stimuli 4916: 4915: 4760:Internet-related 4613: 4612: 4367:Opioid withdrawal 4130: 4129: 4104: 4103: 3705:on 9 October 2012 3656: 3655: 3431:Our World in Data 3425:(December 2019). 3368:978-0-7391-4687-3 3343:978-0-312-35249-3 3228:Comer RJ (2013). 2531:Neuropharmacology 2374:(9566): 1047–53. 2144:Reference Reviews 2039:Sartorius, Norman 1994:Neuropharmacology 1651:Depending on the 1636: 1635: 1629:non-metropolitan 1617:college graduate 1545: 1544: 1488: 1487: 1478:American Indian/ 1469:Pacific Islander 1467:Native Hawaiian/ 1386:hypodermic needle 1343: 1342: 1335: 1261:is a proprietary 1251:with inactivated 878:Opioid dependence 769:extended amygdala 726:nucleus accumbens 692: 691: 612: 611: 320: 319: 209:reverse tolerance 62: 61: 32:Medical condition 5394: 5359: 5358: 5046: 5045: 4927: 4926: 4852:G9a-like protein 4668: 4667: 4640: 4633: 4626: 4617: 4616: 4557:Toluene toxicity 4041:Delirium tremens 3937:Zieve's syndrome 3890: 3889: 3883: 3882: 3746: 3739: 3732: 3723: 3722: 3714: 3712: 3710: 3586: 3585: 3575: 3574: 3572: 3570: 3556: 3550: 3549: 3547: 3545: 3531: 3525: 3524: 3522: 3520: 3511: 3502: 3496: 3495: 3493: 3491: 3485: 3479:. Archived from 3474: 3465: 3459: 3452: 3435: 3434: 3415: 3409: 3408: 3406: 3404: 3384: 3373: 3372: 3354: 3348: 3347: 3335: 3325: 3319: 3318: 3309: 3303: 3302: 3300: 3298: 3289:. Archived from 3283: 3277: 3276: 3245:Biol. Psychiatry 3240: 3234: 3233: 3225: 3210: 3209: 3199: 3189: 3174:Chinese Medicine 3165: 3159: 3158: 3148: 3138: 3123:Chinese Medicine 3114: 3108: 3107: 3104:10.1037/h0100044 3087: 3081: 3080: 3077:10.1037/h0100737 3060: 3054: 3053: 3050:10.1037/h0100376 3032: 3026: 3025: 3019: 3014: 3012: 3004: 3002: 2989: 2983: 2982: 2979:10.1037/h0100155 2962: 2956: 2955: 2945: 2917: 2911: 2910: 2874: 2868: 2856: 2850: 2849: 2821: 2815: 2814: 2786: 2780: 2779: 2751: 2745: 2744: 2734: 2724: 2700: 2694: 2693: 2665: 2659: 2658: 2648: 2624: 2618: 2617: 2603: 2571: 2565: 2564: 2554: 2522: 2516: 2515: 2505: 2473: 2467: 2464: 2458: 2457: 2455: 2453: 2448:on 11 April 2014 2447: 2440: 2432: 2426: 2425: 2423: 2421: 2406: 2400: 2399: 2363: 2357: 2356: 2354: 2352: 2333: 2327: 2326: 2324: 2322: 2303: 2297: 2296: 2279: 2247: 2241: 2240: 2226: 2202: 2196: 2195: 2177: 2168: 2167: 2139: 2133: 2132: 2130: 2128: 2109: 2103: 2102: 2100: 2098: 2079: 2073: 2072: 2066: 2064: 2047: 2034: 2028: 2027: 2017: 1985: 1979: 1978: 1964: 1932: 1926: 1925: 1912: 1880: 1874: 1863: 1854: 1853: 1816: 1665:criminal offence 1557:Education level 1554: 1550: 1499: 1495: 1416: 1412: 1338: 1331: 1327: 1324: 1318: 1294: 1293: 1286: 1049:delirium tremens 828: 817: 762: 716:" (CRF) and the 622: 621: 399: 398: 384:pharmacokinetics 312: 305: 298: 233:delirium tremens 157: 156: 67:, also known as 35: 34: 5402: 5401: 5397: 5396: 5395: 5393: 5392: 5391: 5372: 5371: 5370: 5365: 5347: 5343:Sober companion 5273: 5227:Reagent testing 5203: 5182: 5126: 5120: 5071: 5065: 5040: 5038: 5027: 4956: 4912: 4799:Transcriptional 4791: 4785: 4712: 4698:Methylphenidate 4693:Methamphetamine 4657: 4644: 4614: 4609: 4578: 4539: 4532: 4493: 4411: 4402: 4362:Opioid overdose 4345: 4301: 4272: 4233: 4178: 4126: 4100: 4077: 4006: 3999: 3976:system diseases 3975: 3968: 3949: 3912: 3872: 3844: 3838: 3815:Substance abuse 3758: 3750: 3708: 3706: 3693: 3657: 3652: 3651: 3597: 3583: 3578: 3568: 3566: 3558: 3557: 3553: 3543: 3541: 3533: 3532: 3528: 3518: 3516: 3509: 3503: 3499: 3489: 3487: 3486:on 17 June 2018 3483: 3472: 3466: 3462: 3453: 3438: 3419:Ritchie, Hannah 3416: 3412: 3402: 3400: 3387:Casey, Elaine. 3385: 3376: 3369: 3355: 3351: 3344: 3326: 3322: 3311: 3310: 3306: 3296: 3294: 3285: 3284: 3280: 3241: 3237: 3226: 3213: 3166: 3162: 3115: 3111: 3088: 3084: 3061: 3057: 3033: 3029: 3017: 3015: 3006: 3005: 3000:10.1.1.372.4223 2990: 2986: 2963: 2959: 2918: 2914: 2875: 2871: 2866:Wayback Machine 2857: 2853: 2822: 2818: 2787: 2783: 2752: 2748: 2701: 2697: 2666: 2662: 2625: 2621: 2572: 2568: 2523: 2519: 2474: 2470: 2465: 2461: 2451: 2449: 2445: 2438: 2434: 2433: 2429: 2419: 2417: 2408: 2407: 2403: 2364: 2360: 2350: 2348: 2343:. 10 May 2017. 2335: 2334: 2330: 2320: 2318: 2305: 2304: 2300: 2292: 2248: 2244: 2203: 2199: 2192: 2178: 2171: 2141: 2140: 2136: 2126: 2124: 2111: 2110: 2106: 2096: 2094: 2081: 2080: 2076: 2062: 2060: 2045: 2035: 2031: 1986: 1982: 1933: 1929: 1901:10.1038/nrn3111 1881: 1877: 1864: 1857: 1849: 1848: 1839: 1836: 1831: 1817: 1808: 1804: 1799: 1765: 1761:Substance abuse 1751:Self medication 1726: 1689: 1681:organized crime 1670: 1649: 1480:Alaskan Native 1419:Race/Ethnicity 1403: 1398: 1371:methamphetamine 1339: 1328: 1322: 1319: 1308: 1295: 1291: 1284: 1237: 1223: 1202: 1193: 1168: 1139: 1053:benzodiazepines 1045:benzodiazepines 1032:Pills Anonymous 1008: 964: 852: 847: 838: 823:locus coeruleus 821:pathway in the 812: 801:stress hormones 742:gene expression 734:drug dependence 702: 697: 617: 538:Benzodiazepines 372: 359: 331: 329:Drug withdrawal 325: 316: 216:drug withdrawal 174:biopsychosocial 148:substance abuse 69:drug dependence 46:Drug dependence 33: 28: 25:Substance abuse 17: 12: 11: 5: 5400: 5390: 5389: 5384: 5367: 5366: 5364: 5363: 5352: 5349: 5348: 5346: 5345: 5340: 5339: 5338: 5328: 5327: 5326: 5316: 5311: 5306: 5301: 5296: 5291: 5285: 5283: 5279: 5278: 5275: 5274: 5272: 5271: 5266: 5261: 5256: 5251: 5246: 5241: 5236: 5231: 5230: 5229: 5219: 5213: 5211: 5209:Harm reduction 5205: 5204: 5202: 5201: 5196: 5190: 5188: 5187:Support groups 5184: 5183: 5181: 5180: 5175: 5174: 5173: 5168: 5158: 5153: 5148: 5143: 5142: 5141: 5130: 5128: 5122: 5121: 5119: 5118: 5113: 5108: 5103: 5098: 5093: 5092: 5091: 5086: 5075: 5073: 5067: 5066: 5064: 5063: 5058: 5052: 5050: 5049:Detoxification 5043: 5033: 5032: 5029: 5028: 5026: 5025: 5024: 5023: 5015: 5014: 5013: 5008: 5003: 4998: 4993: 4988: 4986:Benzodiazepine 4983: 4978: 4973: 4964: 4962: 4958: 4957: 4955: 4954: 4949: 4944: 4939: 4933: 4931: 4924: 4918: 4917: 4914: 4913: 4911: 4910: 4909: 4908: 4905: 4900: 4895: 4890: 4885: 4880: 4875: 4868: 4861: 4854: 4849: 4836: 4835: 4834: 4833: 4828: 4823: 4818: 4813: 4808: 4795: 4793: 4787: 4786: 4784: 4783: 4778: 4773: 4772: 4771: 4766: 4758: 4757: 4756: 4751: 4743: 4741:Palatable food 4738: 4737: 4736: 4731: 4722: 4720: 4714: 4713: 4711: 4710: 4705: 4700: 4695: 4690: 4685: 4680: 4674: 4672: 4665: 4659: 4658: 4643: 4642: 4635: 4628: 4620: 4611: 4610: 4608: 4607: 4602: 4601: 4600: 4586: 4584: 4580: 4579: 4577: 4576: 4575: 4574: 4572:Inhalant abuse 4569: 4561: 4560: 4559: 4554: 4544: 4542: 4534: 4533: 4531: 4530: 4529: 4528: 4514: 4513: 4512: 4503: 4501: 4495: 4494: 4492: 4491: 4490: 4489: 4481: 4480: 4479: 4465: 4464: 4463: 4458: 4449: 4448: 4447: 4442: 4432:benzodiazepine 4428: 4427: 4426: 4417: 4415: 4404: 4403: 4401: 4400: 4399: 4398: 4389: 4388: 4387: 4381: 4375: 4369: 4364: 4355: 4353: 4347: 4346: 4344: 4343: 4342: 4341: 4333: 4332: 4331: 4326: 4321: 4311: 4309: 4303: 4302: 4300: 4299: 4298: 4297: 4291: 4282: 4280: 4274: 4273: 4271: 4270: 4269: 4268: 4260: 4259: 4258: 4252: 4243: 4241: 4235: 4234: 4232: 4231: 4230: 4229: 4224: 4218: 4210: 4209: 4208: 4203: 4197: 4188: 4186: 4180: 4179: 4177: 4176: 4175: 4174: 4166: 4165: 4164: 4159: 4154: 4149: 4140: 4138: 4132: 4131: 4128: 4127: 4125: 4124: 4122:Binge drinking 4119: 4112: 4110: 4106: 4105: 4102: 4101: 4099: 4098: 4093: 4087: 4085: 4079: 4078: 4076: 4075: 4069: 4063: 4057: 4052: 4046: 4045: 4044: 4038: 4027: 4022: 4017: 4011: 4009: 4001: 4000: 3998: 3997: 3992: 3987: 3980: 3978: 3970: 3969: 3967: 3966: 3959: 3957: 3951: 3950: 3948: 3947: 3941: 3940: 3939: 3934: 3922: 3920: 3914: 3913: 3911: 3910: 3904: 3898: 3896: 3887: 3880: 3874: 3873: 3871: 3870: 3869: 3868: 3859: 3858: 3857: 3848: 3846: 3840: 3839: 3837: 3836: 3835: 3834: 3821: 3807: 3806: 3805: 3804: 3803: 3797: 3786: 3781: 3766: 3764: 3760: 3759: 3749: 3748: 3741: 3734: 3726: 3720: 3719: 3691: 3684: 3679: 3673: 3668: 3663: 3654: 3653: 3650: 3649: 3638: 3619: 3598: 3593: 3592: 3590: 3589:Classification 3582: 3581:External links 3579: 3577: 3576: 3551: 3526: 3497: 3460: 3436: 3410: 3374: 3367: 3349: 3342: 3320: 3317:. 8 June 2020. 3304: 3278: 3235: 3211: 3160: 3109: 3098:(4): 391–403. 3082: 3055: 3027: 3018:|journal= 2984: 2973:(3): 335–350. 2957: 2928:(4): 367–384. 2912: 2869: 2851: 2816: 2781: 2746: 2695: 2676:(1–3): 121–8. 2660: 2639:(4): 295–300. 2619: 2580:Brain Research 2566: 2517: 2488:(8): 1149–59. 2468: 2459: 2427: 2401: 2358: 2328: 2298: 2262:(4): 363–371. 2242: 2217:(4): 431–443. 2197: 2190: 2169: 2134: 2104: 2074: 2069:Microsoft Bing 2057:Microsoft Word 2029: 2000:(7): 1109–22. 1980: 1927: 1895:(11): 623–37. 1875: 1855: 1829: 1805: 1803: 1800: 1798: 1797: 1792: 1787: 1782: 1777: 1771: 1768:Questionnaires 1764: 1763: 1758: 1753: 1748: 1743: 1738: 1736:Dual diagnosis 1733: 1727: 1725: 1722: 1688: 1685: 1648: 1645: 1634: 1633: 1630: 1627: 1624: 1621: 1618: 1614: 1613: 1610: 1607: 1604: 1601: 1598: 1594: 1593: 1590: 1587: 1584: 1581: 1578: 1574: 1573: 1570: 1567: 1564: 1561: 1558: 1543: 1542: 1539: 1536: 1532: 1531: 1528: 1525: 1521: 1520: 1517: 1514: 1510: 1509: 1506: 1503: 1486: 1485: 1482: 1475: 1474: 1471: 1464: 1463: 1460: 1456: 1455: 1452: 1448: 1447: 1444: 1440: 1439: 1436: 1432: 1431: 1428: 1424: 1423: 1420: 1402: 1399: 1397: 1394: 1341: 1340: 1305:of the subject 1303:worldwide view 1298: 1296: 1289: 1283: 1280: 1279: 1278: 1256: 1236: 1233: 1222: 1219: 1201: 1198: 1192: 1189: 1167: 1164: 1138: 1135: 1063:agent such as 1055:or a taper of 1007: 1004: 976:harm reduction 963: 960: 959: 958: 952: 949: 942: 936: 929: 922: 915: 909: 903: 880: 874: 851: 848: 846: 843: 836: 811: 808: 789:opioid peptide 763:activates the 754:reward pathway 724:" (CREB). The 701: 698: 696: 693: 690: 689: 686: 680: 679: 676: 670: 669: 666: 660: 659: 656: 650: 649: 646: 640: 639: 636: 630: 629: 626: 616: 613: 610: 609: 606: 603: 600: 597: 591: 590: 587: 584: 581: 578: 572: 571: 568: 565: 562: 559: 553: 552: 549: 546: 543: 540: 534: 533: 530: 527: 524: 521: 515: 514: 511: 508: 505: 502: 496: 495: 492: 489: 486: 483: 477: 476: 473: 470: 467: 464: 458: 457: 454: 451: 448: 445: 439: 438: 435: 432: 429: 426: 416: 415: 412: 409: 406: 403: 389:An article in 371: 368: 358: 355: 327:Main article: 324: 321: 318: 317: 315: 314: 307: 300: 292: 289: 288: 287: 286: 278: 270: 262: 253: 244: 236: 220: 212: 200: 192: 190:reward systems 185:addictive drug 181: 162: 161: 91:addictive drug 82:drug addiction 60: 59: 54: 48: 47: 44: 40: 39: 31: 15: 9: 6: 4: 3: 2: 5399: 5388: 5385: 5383: 5380: 5379: 5377: 5362: 5354: 5353: 5350: 5344: 5341: 5337: 5334: 5333: 5332: 5329: 5325: 5322: 5321: 5320: 5317: 5315: 5312: 5310: 5307: 5305: 5302: 5300: 5297: 5295: 5292: 5290: 5287: 5286: 5284: 5280: 5270: 5267: 5265: 5262: 5260: 5257: 5255: 5252: 5250: 5247: 5245: 5242: 5240: 5237: 5235: 5232: 5228: 5225: 5224: 5223: 5222:Drug checking 5220: 5218: 5215: 5214: 5212: 5210: 5206: 5200: 5197: 5195: 5192: 5191: 5189: 5185: 5179: 5176: 5172: 5169: 5167: 5164: 5163: 5162: 5159: 5157: 5154: 5152: 5149: 5147: 5144: 5140: 5137: 5136: 5135: 5132: 5131: 5129: 5123: 5117: 5114: 5112: 5109: 5107: 5104: 5102: 5099: 5097: 5094: 5090: 5087: 5085: 5082: 5081: 5080: 5077: 5076: 5074: 5068: 5062: 5059: 5057: 5054: 5053: 5051: 5047: 5044: 5042: 5034: 5022: 5019: 5018: 5016: 5012: 5009: 5007: 5004: 5002: 4999: 4997: 4994: 4992: 4989: 4987: 4984: 4982: 4979: 4977: 4974: 4972: 4969: 4968: 4966: 4965: 4963: 4959: 4953: 4950: 4948: 4945: 4943: 4940: 4938: 4935: 4934: 4932: 4928: 4925: 4923: 4919: 4906: 4904: 4901: 4899: 4896: 4894: 4891: 4889: 4886: 4884: 4881: 4879: 4876: 4874: 4873: 4869: 4867: 4866: 4862: 4860: 4859: 4855: 4853: 4850: 4848: 4847: 4843: 4842: 4841: 4838: 4837: 4832: 4829: 4827: 4824: 4822: 4819: 4817: 4814: 4812: 4809: 4807: 4806: 4802: 4801: 4800: 4797: 4796: 4794: 4788: 4782: 4779: 4777: 4774: 4770: 4767: 4765: 4762: 4761: 4759: 4755: 4752: 4750: 4747: 4746: 4744: 4742: 4739: 4735: 4732: 4730: 4727: 4726: 4724: 4723: 4721: 4719: 4715: 4709: 4706: 4704: 4701: 4699: 4696: 4694: 4691: 4689: 4686: 4684: 4681: 4679: 4676: 4675: 4673: 4669: 4666: 4664: 4660: 4656: 4652: 4648: 4647:Reinforcement 4641: 4636: 4634: 4629: 4627: 4622: 4621: 4618: 4606: 4603: 4599: 4596: 4595: 4593: 4592: 4588: 4587: 4585: 4581: 4573: 4570: 4568: 4565: 4564: 4562: 4558: 4555: 4552: 4549: 4548: 4546: 4545: 4543: 4541: 4535: 4527: 4524: 4523: 4521: 4519: 4515: 4511: 4508: 4507: 4505: 4504: 4502: 4500: 4496: 4488: 4485: 4484: 4482: 4478: 4475: 4474: 4472: 4470: 4466: 4462: 4459: 4456: 4453: 4452: 4450: 4446: 4443: 4441: 4438: 4437: 4435: 4433: 4429: 4425: 4422: 4421: 4419: 4418: 4416: 4414: 4409: 4405: 4396: 4393: 4392: 4390: 4385: 4382: 4379: 4376: 4373: 4370: 4368: 4365: 4363: 4360: 4359: 4357: 4356: 4354: 4352: 4348: 4340: 4337: 4336: 4334: 4330: 4327: 4325: 4322: 4319: 4316: 4315: 4313: 4312: 4310: 4308: 4304: 4295: 4292: 4290: 4287: 4286: 4284: 4283: 4281: 4279: 4275: 4267: 4264: 4263: 4261: 4256: 4253: 4251: 4248: 4247: 4245: 4244: 4242: 4240: 4236: 4228: 4225: 4222: 4219: 4217: 4214: 4213: 4211: 4207: 4204: 4201: 4198: 4196: 4193: 4192: 4190: 4189: 4187: 4185: 4181: 4173: 4170: 4169: 4167: 4163: 4160: 4158: 4155: 4153: 4150: 4148: 4145: 4144: 4142: 4141: 4139: 4137: 4133: 4123: 4120: 4117: 4114: 4113: 4111: 4107: 4097: 4094: 4092: 4089: 4088: 4086: 4084: 4080: 4073: 4070: 4067: 4064: 4061: 4058: 4056: 4053: 4050: 4047: 4042: 4039: 4037: 4034: 4033: 4031: 4028: 4026: 4023: 4021: 4018: 4016: 4013: 4012: 4010: 4008: 4002: 3996: 3993: 3991: 3988: 3985: 3982: 3981: 3979: 3977: 3971: 3964: 3961: 3960: 3958: 3956: 3952: 3945: 3942: 3938: 3935: 3933: 3930: 3929: 3927: 3924: 3923: 3921: 3919: 3915: 3908: 3905: 3903: 3900: 3899: 3897: 3895: 3891: 3888: 3884: 3881: 3879: 3875: 3866: 3863: 3862: 3860: 3856: 3853: 3852: 3850: 3849: 3847: 3845:substance use 3841: 3833: 3829: 3825: 3822: 3820: 3816: 3813: 3812: 3811: 3808: 3801: 3798: 3796: 3793: 3792: 3790: 3787: 3785: 3782: 3780: 3779:Drug overdose 3776: 3773: 3772: 3771: 3768: 3767: 3765: 3761: 3757: 3754: 3747: 3742: 3740: 3735: 3733: 3728: 3727: 3724: 3718: 3704: 3700: 3696: 3692: 3689: 3685: 3683: 3680: 3677: 3674: 3672: 3669: 3667: 3664: 3662: 3659: 3658: 3648: 3644: 3643: 3639: 3637: 3633: 3629: 3628: 3624: 3620: 3617: 3613: 3609: 3608: 3604: 3600: 3599: 3596: 3591: 3587: 3565: 3561: 3555: 3540: 3536: 3530: 3515: 3508: 3501: 3482: 3478: 3471: 3464: 3457: 3451: 3449: 3447: 3445: 3443: 3441: 3432: 3428: 3424: 3420: 3414: 3398: 3394: 3390: 3383: 3381: 3379: 3370: 3364: 3360: 3353: 3345: 3339: 3336:. Macmillan. 3334: 3333: 3324: 3316: 3315: 3308: 3292: 3288: 3282: 3274: 3270: 3266: 3262: 3258: 3254: 3251:(2): 158–64. 3250: 3246: 3239: 3231: 3224: 3222: 3220: 3218: 3216: 3207: 3203: 3198: 3193: 3188: 3183: 3179: 3175: 3171: 3164: 3156: 3152: 3147: 3142: 3137: 3132: 3128: 3124: 3120: 3113: 3105: 3101: 3097: 3093: 3086: 3078: 3074: 3071:(2): 90–100. 3070: 3066: 3059: 3051: 3047: 3043: 3039: 3031: 3023: 3010: 3001: 2996: 2988: 2980: 2976: 2972: 2968: 2961: 2953: 2949: 2944: 2939: 2935: 2931: 2927: 2923: 2916: 2908: 2904: 2900: 2896: 2892: 2888: 2884: 2880: 2873: 2867: 2863: 2860: 2855: 2847: 2843: 2839: 2835: 2831: 2827: 2820: 2812: 2808: 2804: 2800: 2796: 2792: 2785: 2777: 2773: 2769: 2765: 2761: 2757: 2750: 2742: 2738: 2733: 2728: 2723: 2718: 2714: 2710: 2706: 2699: 2691: 2687: 2683: 2679: 2675: 2671: 2664: 2656: 2652: 2647: 2642: 2638: 2634: 2630: 2623: 2616: 2611: 2607: 2602: 2597: 2593: 2589: 2585: 2581: 2577: 2570: 2562: 2558: 2553: 2548: 2544: 2540: 2536: 2532: 2528: 2521: 2513: 2509: 2504: 2499: 2495: 2491: 2487: 2483: 2479: 2472: 2463: 2444: 2437: 2431: 2415: 2411: 2405: 2397: 2393: 2389: 2385: 2381: 2377: 2373: 2369: 2362: 2346: 2342: 2338: 2332: 2316: 2312: 2308: 2302: 2295: 2287: 2283: 2278: 2273: 2269: 2265: 2261: 2257: 2253: 2246: 2239: 2234: 2230: 2225: 2220: 2216: 2212: 2208: 2201: 2193: 2191:9780071481274 2187: 2183: 2176: 2174: 2165: 2161: 2157: 2153: 2149: 2145: 2138: 2122: 2118: 2114: 2108: 2092: 2088: 2084: 2078: 2070: 2058: 2054: 2053: 2044: 2040: 2033: 2025: 2021: 2016: 2011: 2007: 2003: 1999: 1995: 1991: 1984: 1977: 1972: 1968: 1963: 1958: 1954: 1950: 1946: 1942: 1938: 1931: 1924: 1920: 1916: 1911: 1906: 1902: 1898: 1894: 1890: 1886: 1879: 1873: 1869: 1868: 1862: 1860: 1852: 1846: 1842: 1832: 1830:9780071481274 1826: 1822: 1815: 1813: 1811: 1806: 1796: 1793: 1791: 1788: 1786: 1783: 1781: 1778: 1776: 1773: 1772: 1770: 1769: 1762: 1759: 1757: 1754: 1752: 1749: 1747: 1744: 1742: 1739: 1737: 1734: 1732: 1729: 1728: 1721: 1718: 1712: 1710: 1706: 1700: 1698: 1694: 1687:United States 1684: 1682: 1678: 1673: 1668: 1666: 1661: 1656: 1654: 1644: 1641: 1631: 1628: 1625: 1622: 1619: 1616: 1615: 1611: 1608: 1605: 1602: 1599: 1596: 1595: 1591: 1588: 1585: 1582: 1579: 1576: 1575: 1571: 1568: 1565: 1562: 1559: 1556: 1555: 1549: 1540: 1537: 1534: 1533: 1529: 1526: 1523: 1522: 1518: 1515: 1513:12 and older 1512: 1511: 1507: 1504: 1501: 1500: 1494: 1493: 1483: 1481: 1477: 1476: 1472: 1470: 1466: 1465: 1461: 1458: 1457: 1453: 1450: 1449: 1445: 1442: 1441: 1437: 1434: 1433: 1429: 1426: 1425: 1421: 1418: 1417: 1411: 1409: 1393: 1389: 1387: 1382: 1377: 1374: 1372: 1368: 1364: 1360: 1356: 1352: 1348: 1337: 1334: 1326: 1323:February 2014 1316: 1312: 1306: 1304: 1297: 1288: 1287: 1276: 1272: 1268: 1264: 1260: 1257: 1254: 1250: 1246: 1243:is an active 1242: 1239: 1238: 1232: 1229: 1218: 1215: 1211: 1208: 1197: 1188: 1186: 1180: 1175: 1173: 1163: 1160: 1156: 1152: 1148: 1144: 1134: 1132: 1131:disease model 1128: 1124: 1118: 1116: 1112: 1111:buprenorphine 1108: 1104: 1100: 1096: 1091: 1087: 1086:alpha-agonist 1083: 1078: 1074: 1070: 1066: 1062: 1061:antiepileptic 1058: 1057:phenobarbital 1054: 1050: 1046: 1041: 1037: 1033: 1029: 1025: 1021: 1016: 1014: 1003: 1001: 997: 993: 987: 983: 979: 977: 973: 969: 957: 953: 950: 947: 946:Phencyclidine 943: 941: 937: 934: 930: 927: 923: 920: 916: 914: 910: 908: 904: 901: 897: 893: 889: 885: 881: 879: 875: 873: 869: 868: 867: 865: 861: 857: 842: 839: 832: 824: 820: 807: 804: 802: 798: 797:reward system 794: 790: 786: 782: 778: 774: 770: 766: 757: 755: 751: 747: 743: 739: 735: 732:component of 731: 730:psychological 727: 723: 719: 715: 711: 707: 687: 685: 682: 681: 677: 675: 672: 671: 667: 665: 662: 661: 657: 655: 652: 651: 647: 645: 642: 641: 637: 635: 632: 631: 627: 624: 623: 620: 615:Capture rates 607: 604: 601: 598: 596: 593: 592: 588: 585: 582: 579: 577: 574: 573: 569: 566: 563: 560: 558: 555: 554: 550: 547: 544: 541: 539: 536: 535: 531: 528: 525: 522: 520: 517: 516: 512: 509: 506: 503: 501: 498: 497: 493: 490: 487: 484: 482: 479: 478: 474: 471: 468: 465: 463: 460: 459: 455: 452: 449: 446: 444: 441: 440: 436: 433: 430: 427: 425: 421: 418: 417: 413: 410: 407: 404: 401: 400: 397: 394: 393: 387: 385: 381: 377: 363: 354: 352: 347: 345: 341: 337: 330: 313: 308: 306: 301: 299: 294: 293: 290: 284: 283: 279: 276: 275: 271: 268: 267: 266:sensitization 263: 260: 258: 254: 251: 249: 245: 242: 241: 237: 234: 230: 226: 225: 221: 218: 217: 213: 210: 206: 205: 201: 198: 197: 193: 191: 187: 186: 182: 179: 175: 171: 170: 166: 165: 163: 158: 155: 153: 149: 145: 140: 136: 132: 131: 126: 123: 119: 115: 110: 108: 104: 100: 96: 92: 88: 84: 83: 78: 74: 70: 66: 58: 55: 53: 49: 45: 41: 36: 30: 26: 22: 4921: 4870: 4863: 4856: 4844: 4803: 4745:Sex-related 4654: 4589: 4516: 4467: 4430: 4278:Hallucinogen 4005:Neurological 3831: 3753:Psychoactive 3707:. Retrieved 3703:the original 3699:apps.who.int 3698: 3640: 3621: 3601: 3567:. Retrieved 3563: 3554: 3542:. Retrieved 3539:usatoday.com 3538: 3529: 3517:. Retrieved 3513: 3500: 3488:. Retrieved 3481:the original 3476: 3463: 3430: 3413: 3401:. Retrieved 3392: 3358: 3352: 3331: 3323: 3313: 3307: 3295:. Retrieved 3291:the original 3281: 3248: 3244: 3238: 3229: 3177: 3173: 3163: 3126: 3122: 3112: 3095: 3091: 3085: 3068: 3064: 3058: 3044:(1): 80–90. 3041: 3037: 3030: 3009:cite journal 2987: 2970: 2966: 2960: 2925: 2921: 2915: 2882: 2878: 2872: 2854: 2832:(1): 75–83. 2829: 2825: 2819: 2797:(3): 251–8. 2794: 2790: 2784: 2759: 2755: 2749: 2712: 2708: 2698: 2673: 2669: 2663: 2636: 2632: 2622: 2613: 2583: 2579: 2569: 2534: 2530: 2520: 2485: 2481: 2471: 2462: 2450:. Retrieved 2443:the original 2430: 2418:. Retrieved 2404: 2371: 2367: 2361: 2349:. Retrieved 2341:sheknows.com 2340: 2331: 2319:. Retrieved 2310: 2301: 2289: 2259: 2255: 2245: 2236: 2214: 2210: 2200: 2181: 2147: 2143: 2137: 2125:. 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