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1. "The Stroop effect at 80: The competition between stimulus control and cognitive control". J Exp Anal Behav 105 (1): 3–13. 2016. doi:10.1002/jeab.194. PMID 26781048. "Today, arguably more than at any time in history, the constructs of attention, executive functioning, and cognitive control seem to be pervasive and preeminent in research and theory. Even within the cognitive framework, however, there has long been an understanding that behavior is multiply determined, and that many responses are relatively automatic, unattended, contention-scheduled, and habitual. Indeed, the cognitive flexibility, response inhibition, and self-regulation that appear to be hallmarks of cognitive control are noteworthy only in contrast to responses that are relatively rigid, associative, and involuntary.".  https://dx.doi.org/10.1002%2Fjeab.194
2. "Executive functions". Annu Rev Psychol 64: 135–68. 2013. doi:10.1146/annurev-psych-113011-143750. PMID 23020641. "Core EFs are inhibition [response inhibition (self-control – resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)], working memory, and cognitive flexibility (including creatively thinking "outside the box," seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances). ... EFs and prefrontal cortex are the first to suffer, and suffer disproportionately, if something is not right in your life. They suffer first, and most, if you are stressed (Arnsten 1998, Liston et al. 2009, Oaten & Cheng 2005), sad (Hirt et al. 2008, von Hecker & Meiser 2005), lonely (Baumeister et al. 2002, Cacioppo & Patrick 2008, Campbell et al. 2006, Tun et al. 2012), sleep deprived (Barnes et al. 2012, Huang et al. 2007), or not physically fit (Best 2010, Chaddock et al. 2011, Hillman et al. 2008). Any of these can cause you to appear to have a disorder of EFs, such as ADHD, when you do not. You can see the deleterious effects of stress, sadness, loneliness, and lack of physical health or fitness at the physiological and neuroanatomical level in prefrontal cortex and at the behavioral level in worse EFs (poorer reasoning and problem solving, forgetting things, and impaired ability to exercise discipline and self-control). ...EFs can be improved (Diamond & Lee 2011, Klingberg 2010). ... At any age across the life cycle EFs can be improved, including in the elderly and in infants. There has been much work with excellent results on improving EFs in the elderly by improving physical fitness (Erickson & Kramer 2009, Voss et al. 2011) ... Inhibitory control (one of the core EFs) involves being able to control one's attention, behavior, thoughts, and/or emotions to override a strong internal predisposition or external lure, and instead do what's more appropriate or needed. Without inhibitory control we would be at the mercy of impulses, old habits of thought or action (conditioned responses), and/or stimuli in the environment that pull us this way or that. Thus, inhibitory control makes it possible for us to change and for us to choose how we react and how we behave rather than being unthinking creatures of habit. It doesn’t make it easy. Indeed, we usually are creatures of habit and our behavior is under the control of environmental stimuli far more than we usually realize, but having the ability to exercise inhibitory control creates the possibility of change and choice. ... The subthalamic nucleus appears to play a critical role in preventing such impulsive or premature responding (Frank 2006).".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4084861
3. "Chapter 13: Higher Cognitive Function and Behavioral Control". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. 2009. pp. 313–21. ISBN 978-0-07-148127-4. " • Executive function, the cognitive control of behavior, depends on the prefrontal cortex, which is highly developed in higher primates and especially humans. • Working memory is a short-term, capacity-limited cognitive buffer that stores information and permits its manipulation to guide decision-making and behavior. ...These diverse inputs and back projections to both cortical and subcortical structures put the prefrontal cortex in a position to exert what is often called "top-down" control or cognitive control of behavior. ... The prefrontal cortex receives inputs not only from other cortical regions, including association cortex, but also, via the thalamus, inputs from subcortical structures subserving emotion and motivation, such as the amygdala (Chapter 14) and ventral striatum (or nucleus accumbens; Chapter 15). ...In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 15), or in attention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result. ... ADHD can be conceptualized as a disorder of executive function; specifically, ADHD is characterized by reduced ability to exert and maintain cognitive control of behavior. Compared with healthy individuals, those with ADHD have diminished ability to suppress inappropriate prepotent responses to stimuli (impaired response inhibition) and diminished ability to inhibit responses to irrelevant stimuli (impaired interference suppression). ... Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the striatum) in tasks that demand inhibitory control of behavior. Subjects with ADHD exhibit less activation of the medial prefrontal cortex than healthy controls even when they succeed in such tasks and utilize different circuits. ... Early results with structural MRI show thinning of the cerebral cortex in ADHD subjects compared with age-matched controls in prefrontal cortex and posterior parietal cortex, areas involved in working memory and attention." 
4. "Chapter 15: Reinforcement and Addictive Disorders". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. 2009. pp. 364–65, 375. ISBN 978-0-07-148127-4. "The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. ...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." 
5. "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology 61 (7): 1109–22. December 2011. doi:10.1016/j.neuropharm.2011.03.010. 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: Summary of plasticity observed following exposure to drug or natural reinforcers" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139704/table/T1/
6. "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–37. November 2011. doi:10.1038/nrn3111. PMID 21989194. "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.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3272277
7. "Sexual addiction or hypersexual disorder: different terms for the same problem? A review of the literature". Curr. Pharm. Des. 20 (25): 4012–20. 2014. 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.".  https://dx.doi.org/10.2174%2F13816128113199990619
8. "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". The Journal of Neuroscience 33 (8): 3434–42. February 2013. doi:10.1523/JNEUROSCI.4881-12.2013. 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".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3865508
9. "Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats". Neuropharmacology 101: 154–64. February 2016. doi:10.1016/j.neuropharm.2015.09.023. PMID 26391065.  https://dx.doi.org/10.1016%2Fj.neuropharm.2015.09.023
10. Coffee, tea, chocolate, and the brain.. Boca Raton: CRC Press. 2004. pp. 203–218. ISBN 9780429211928. 
11. "Food addiction in the light of DSM-5". Nutrients 6 (9): 3653–71. September 2014. doi:10.3390/nu6093653. PMID 25230209.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4179181
12. error
13. Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience 15 (4): 431–443. PMID 24459410. "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, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] 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.41 ... 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.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3898681
14. "Mechanisms of transgenerational inheritance of addictive-like behaviors". Neuroscience 264: 198–206. 2014. doi:10.1016/j.neuroscience.2013.07.064. PMID 23920159. "However, the components that are responsible for the heritability of characteristics that make an individual more susceptible to drug addiction in humans remain largely unknown given that patterns of inheritance cannot be explained by simple genetic mechanisms (Cloninger et al., 1981; Schuckit et al., 1972). The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse. ...The evidence presented here demonstrates that rapid environmental adaptation occurs following exposure to a number of stimuli. Epigenetic mechanisms represent the key components by which the environment can influence genetics, and they provide the missing link between genetic heritability and environmental influences on the behavioral and physiological phenotypes of the offspring.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3872494
15. Mayfield, R D; Harris, R A; Schuckit, M A (May 2008). "Genetic factors influencing alcohol dependence: Genetic factors and alcohol dependence". British Journal of Pharmacology 154 (2): 275–287. doi:10.1038/bjp.2008.88. PMID 18362899.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2442454
16. "A twin-family study of alcoholism in women". Am J Psychiatry 151 (5): 707–15. May 1994. doi:10.1176/ajp.151.5.707. PMID 8166312.  https://dx.doi.org/10.1176%2Fajp.151.5.707
17. "Low frequency genetic variants in the μ-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine". Neuroscience Letters 542: 71–75. 2013. doi:10.1016/j.neulet.2013.02.018. PMID 23454283.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3640707
18. "Implications of genome wide association studies for addiction: are our a priori assumptions all wrong?". Pharmacology & Therapeutics 140 (3): 267–79. December 2013. doi:10.1016/j.pharmthera.2013.07.006. PMID 23872493.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3797854
19. "Genetics of alcoholism". Alcohol Health and Research World: 1–11. http://psycnet.apa.org/record/1993-22020-001. Retrieved 13 December 2017. 
20. "The Genetics of Addiction – Is Addiction a Disease?". I Want to Change My Life. https://www.addictionsandrecovery.org/is-addiction-a-disease.htm. 
21. "Overdose Death Rates". National Institute on Drug Abuse. 9 August 2018. https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates. 
22. "Overdose Deaths Accelerating During Covid-19". Centers For Disease Control Prevention. 18 December 2020. https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html. 
23. "How the COVID-19 pandemic impacts tobacco addiction: Changes in smoking behavior and associations with well-being". Addictive Behaviors 119: 106917. August 2021. doi:10.1016/j.addbeh.2021.106917. PMID 33862579.  https://dx.doi.org/10.1016%2Fj.addbeh.2021.106917
24. "What are risk factors and protective factors?". National Institute on Drug Abuse. https://www.drugabuse.gov/publications/preventing-drug-abuse-among-children-adolescents/chapter-1-risk-factors-protective-factors/what-are-risk-factors. 
25. "Understanding Drug Use and Addiction" (in en). National Institute on Drug Abuse. 6 June 2018. https://www.drugabuse.gov/publications/drugfacts/understanding-drug-use-addiction. 
26. "Brain Change in Addiction as Learning, Not Disease". The New England Journal of Medicine 379 (16): 1551–1560. October 2018. doi:10.1056/NEJMra1602872. PMID 30332573. "Addictive activities are determined neither solely by brain changes nor solely by social conditions ... the narrowing seen in addiction takes place within the behavioral repertoire, the social surround, and the brain — all at the same time.".  https://dx.doi.org/10.1056%2FNEJMra1602872
27. "Adverse Childhood Experiences". Rockville, Maryland, United States: Substance Abuse and Mental Health Services Administration. http://www.samhsa.gov/capt/practicing-effective-prevention/prevention-behavioral-health/adverse-childhood-experiences. 
28. "The role of early life stress as a predictor for alcohol and drug dependence". Psychopharmacology 214 (1): 17–31. March 2011. doi:10.1007/s00213-010-1916-6. PMID 20596857.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3005022
29. "Environmental Risk Factors". https://learn.genetics.utah.edu/content/addiction/environment/. 
30. "The adolescent brain and age-related behavioral manifestations". Neuroscience and Biobehavioral Reviews 24 (4): 417–63. June 2000. doi:10.1016/s0149-7634(00)00014-2. PMID 10817843.  https://dx.doi.org/10.1016%2Fs0149-7634%2800%2900014-2
31. "Neurobiology of adolescent substance use and addictive behaviors: treatment implications". Adolescent Medicine 25 (1): 15–32. April 2014. PMID 25022184.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4446977
32. "Evaluation of the effectiveness of adolescent drug abuse treatment, assessment of risks for relapse, and promising approaches for relapse prevention". The International Journal of the Addictions 25 (9A–10A): 1085–140. 1990. doi:10.3109/10826089109081039. PMID 2131328.  https://dx.doi.org/10.3109%2F10826089109081039
33. "Practitioner review: adolescent alcohol use disorders: assessment and treatment issues". Journal of Child Psychology and Psychiatry, and Allied Disciplines 49 (11): 1131–54. November 2008. doi:10.1111/j.1469-7610.2008.01934.x. PMID 19017028.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4113213
34. "Age and Substance Abuse – Alcohol Rehab". http://alcoholrehab.com/drug-addiction/age-and-substance-abuse/. 
35. "Nationwide Trends". National Institute on Drug Abuse. June 2015. http://www.drugabuse.gov/publications/drugfacts/nationwide-trends. 
36. "Addiction Statistics – Facts on Drug and Alcohol Addiction". AddictionCenter. https://www.addictioncenter.com/addiction/addiction-statistics/. 
37. SAMHSA. "Risk and Protective Factors". Substance Abuse and Mental Health Administration. https://www.samhsa.gov/capt/practicing-effective-prevention/prevention-behavioral-health/risk-protective-factors. 
38. "Infographic – Risk Factors of Addiction | Recovery Research Institute". http://www.recoveryanswers.org/pressrelease/infographic-risk-factors-addiction/. 
39. "Drug addiction Risk factors – Mayo Clinic". http://www.mayoclinic.org/diseases-conditions/drug-addiction/basics/risk-factors/con-20020970. 
40. "The Connection Between Mental Illness and Substance Abuse | Dual Diagnosis". Dual Diagnosis. https://www.dualdiagnosis.org/mental-health-and-addiction/the-connection/. 
41. "Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism". Mol. Neurobiol. 53 (9): 6367–76. 2015. doi:10.1007/s12035-015-9526-2. PMID 26572641.  https://dx.doi.org/10.1007%2Fs12035-015-9526-2
42. According to a review of experimental animal models that examined the transgenerational epigenetic inheritance of epigenetic marks that occur in addiction, alterations in histone acetylation – specifically, di-acetylation of lysine residues 9 and 14 on histone 3 (i.e., H3K9ac2 and H3K14ac2) in association with BDNF gene promoters – have been shown to occur within the medial prefrontal cortex (mPFC), testes, and sperm of cocaine-addicted male rats.[40] These epigenetic alterations in the rat mPFC result in increased BDNF gene expression within the mPFC, which in turn blunts the rewarding properties of cocaine and reduces cocaine self-administration.[40] The male but not female offspring of these cocaine-exposed rats inherited both epigenetic marks (i.e., di-acetylation of lysine residues 9 and 14 on histone 3) within mPFC neurons, the corresponding increase in BDNF expression within mPFC neurons, and the behavioral phenotype associated with these effects (i.e., a reduction in cocaine reward, resulting in reduced cocaine-seeking by these male offspring).[40] Consequently, the transmission of these two cocaine-induced epigenetic alterations (i.e., H3K9ac2 and H3K14ac2) in rats from male fathers to male offspring served to reduce the offspring's risk of developing an addiction to cocaine.[40] (As of 2018) neither the heritability of these epigenetic marks in humans nor the behavioral effects of the marks within human mPFC neurons has been established.[40]
43. "Drug abuse liability" (in en). https://www.cambridgecognition.com/research-areas/drug-abuse-liability-research/. 
44. National Institute on Drug Abuse (2020-08-20). "Commonly Used Drugs Charts" (in en). https://www.drugabuse.gov/drug-topics/commonly-used-drugs-charts. 
45. Renthal W, Nestler EJ (September 2009). "Chromatin regulation in drug addiction and depression". Dialogues in Clinical Neuroscience 11 (3): 257–268. PMID 19877494. "[Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its targets. This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the histone acetyltransferase, CREB binding protein (CBP) to acetylate histones and facilitate gene activation. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure. ΔFosB is also upregulated by chronic psychostimulant treatments, and is known to activate certain genes (eg, cdk5) and repress others (eg, c-fos) where it recruits HDAC1 as a corepressor. ... Chronic exposure to psychostimulants increases glutamatergic [signaling] from the prefrontal cortex to the NAc. Glutamatergic signaling elevates Ca2+ levels in NAc postsynaptic elements where it activates CaMK (calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5.". Figure 2: Psychostimulant-induced signaling events https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834246/figure/DialoguesClinNeurosci-11-257-g002/
46. "Co-transmission of dopamine and glutamate". The Journal of General Physiology 139 (1): 93–96. January 2012. doi:10.1085/jgp.201110659. PMID 22200950. "Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex (PFC), as well as projections from midbrain dopamine neurons. Previous studies have demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses (Goto and Grace, 2005). The converse was also shown to be true; stimulation at PFC potentiates PFC–NAc synapses but depresses hippocampal–NAc synapses. In light of the new functional evidence of midbrain dopamine/glutamate co-transmission (references above), new experiments of NAc function will have to test whether midbrain glutamatergic inputs bias or filter either limbic or cortical inputs to guide goal-directed behavior.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3250102
47. Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)". KEGG Pathway. http://www.genome.jp/kegg-bin/show_pathway?hsa05031+2354. Retrieved 31 October 2014. "Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. ... Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain." 
48. "Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat". Molecular Neurobiology 51 (2): 696–717. 2015. doi:10.1007/s12035-014-8776-8. PMID 24939695. "Figure 1".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4359351
49. Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews Neuroscience 12 (11): 623–637. doi:10.1038/nrn3111. PMID 21989194. "ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.". Figure 4: Epigenetic basis of drug regulation of gene expression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272277/figure/F4/
50. Nestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clinical Psychopharmacology and Neuroscience 10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMID 23430970. "The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB ... In contrast, the ability of ΔFosB to repress the c-Fos gene occurs in concert with the recruitment of a histone deacetylase and presumably several other repressive proteins such as a repressive histone methyltransferase".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3569166
51. Nestler EJ (October 2008). "Transcriptional mechanisms of addiction: Role of ΔFosB". Philosophical Transactions of the Royal Society B: Biological Sciences 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. 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".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2607320
52. "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–98. 2006. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.  https://dx.doi.org/10.1146%2Fannurev.neuro.29.051605.113009
53. "Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants". Prog. Neurobiol. 100: 60–80. January 2013. doi:10.1016/j.pneurobio.2012.10.001. PMID 23085425.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3525776
54. A decrease in aversion sensitivity, in simpler terms, means that an individual's behavior is less likely to be influenced by undesirable outcomes.
55. "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am. J. Drug Alcohol Abuse 40 (6): 428–37. November 2014. doi:10.3109/00952990.2014.933840. PMID 25083822. "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. ...ConclusionsΔFosB 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.".  https://dx.doi.org/10.3109%2F00952990.2014.933840
56. Kanehisa Laboratories (2 August 2013). "Alcoholism – Homo sapiens (human)". KEGG Pathway. http://www.genome.jp/kegg-bin/show_pathway?hsa05034+2354. 
57. "Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens". Proc. Natl. Acad. Sci. USA 106 (8): 2915–20. February 2009. doi:10.1073/pnas.0813179106. PMID 19202072. Bibcode: 2009PNAS..106.2915K.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2650365
58. "Epigenetic mechanisms of drug addiction". Neuropharmacology 76 Pt B: 259–68. January 2014. doi:10.1016/j.neuropharm.2013.04.004. PMID 23643695. "Short-term increases in histone acetylation generally promote behavioral responses to the drugs, while sustained increases oppose cocaine's effects, based on the actions of systemic or intra-NAc administration of HDAC inhibitors. ... Genetic or pharmacological blockade of G9a in the NAc potentiates behavioral responses to cocaine and opiates, whereas increasing G9a function exerts the opposite effect (Maze et al., 2010; Sun et al., 2012a). Such drug-induced downregulation of G9a and H3K9me2 also sensitizes animals to the deleterious effects of subsequent chronic stress (Covington et al., 2011). Downregulation of G9a increases the dendritic arborization of NAc neurons, and is associated with increased expression of numerous proteins implicated in synaptic function, which directly connects altered G9a/H3K9me2 in the synaptic plasticity associated with addiction (Maze et al., 2010).G9a appears to be a critical control point for epigenetic regulation in NAc, as we know it functions in two negative feedback loops. It opposes the induction of ΔFosB, a long-lasting transcription factor important for drug addiction (Robison and Nestler, 2011), while ΔFosB in turn suppresses G9a expression (Maze et al., 2010; Sun et al., 2012a). ... Also, G9a is induced in NAc upon prolonged HDAC inhibition, which explains the paradoxical attenuation of cocaine's behavioral effects seen under these conditions, as noted above (Kennedy et al., 2013). GABAA receptor subunit genes are among those that are controlled by this feedback loop. Thus, chronic cocaine, or prolonged HDAC inhibition, induces several GABAA receptor subunits in NAc, which is associated with increased frequency of inhibitory postsynaptic currents (IPSCs). In striking contrast, combined exposure to cocaine and HDAC inhibition, which triggers the induction of G9a and increased global levels of H3K9me2, leads to blockade of GABAA receptor and IPSC regulation.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3766384
59. "Epigenetic regulation in drug addiction". Ann. Agric. Environ. Med. 19 (3): 491–96. 2012. PMID 23020045. http://www.aaem.pl/fulltext.php?ICID=1010966. "For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription". 
60. "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". Journal of Psychoactive Drugs 44 (1): 38–55. 2012. doi:10.1080/02791072.2012.662112. PMID 22641964. "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, 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.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4040958
61. "Chapter 15: Reinforcement and addictive disorders". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. 2009. pp. 384–85. ISBN 978-0-07-148127-4. 
62. "Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes". Psychopharmacology 107 (2–3): 160–74. 1992. doi:10.1007/bf02245133. PMID 1615120.  https://dx.doi.org/10.1007%2Fbf02245133
63. "Synaptic plasticity and addiction". Nature Reviews. Neuroscience 8 (11): 844–58. November 2007. doi:10.1038/nrn2234. PMID 17948030.  https://dx.doi.org/10.1038%2Fnrn2234
64. "Cholinergic interneurons control local circuit activity and cocaine conditioning". Science 330 (6011): 1677–81. December 2010. doi:10.1126/science.1193771. PMID 21164015. Bibcode: 2010Sci...330.1677W.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3142356
65. "DeltaFosB: a sustained molecular switch for addiction". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11042–46. September 2001. doi:10.1073/pnas.191352698. PMID 11572966. Bibcode: 2001PNAS...9811042N. "Although the ΔFosB signal is relatively long-lived, it is not permanent. ΔFosB degrades gradually and can no longer be detected in brain after 1–2 months of drug withdrawal ... Indeed, ΔFosB is the longest-lived adaptation known to occur in adult brain, not only in response to drugs of abuse, but to any other perturbation (that doesn't involve lesions) as well.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=58680
66. "Synaptic plasticity and drug addiction". Current Opinion in Pharmacology 5 (1): 20–25. 2005. doi:10.1016/j.coph.2004.08.011. PMID 15661621.  https://dx.doi.org/10.1016%2Fj.coph.2004.08.011
67. "Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and stem cell biology". Hippocampus 16 (3): 271–86. 2006. doi:10.1002/hipo.20161. PMID 16411230.  https://dx.doi.org/10.1002%2Fhipo.20161
68. Pharmacology. Edinburgh: Churchill Livingstone. 2003. p. 596. ISBN 978-0-443-07145-4. 
69. "Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens". J. Neurosci. 27 (30): 7921–28. 2007. doi:10.1523/JNEUROSCI.1859-07.2007. PMID 17652583.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6672735
70. "The neural basis of addiction: a pathology of motivation and choice". The American Journal of Psychiatry 162 (8): 1403–13. August 2005. doi:10.1176/appi.ajp.162.8.1403. PMID 16055761.  https://dx.doi.org/10.1176%2Fappi.ajp.162.8.1403
71. "Amygdala-prefrontal cortical circuitry regulates effort-based decision making". Cerebral Cortex 17 (2): 251–60. February 2007. doi:10.1093/cercor/bhj143. PMID 16495432.  https://dx.doi.org/10.1093%2Fcercor%2Fbhj143
72. "Role of cues and contexts on drug-seeking behaviour". British Journal of Pharmacology 171 (20): 4636–72. October 2014. doi:10.1111/bph.12735. PMID 24749941.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4209936
73. "Dopamine in drug abuse and addiction: results of imaging studies and treatment implications". Arch. Neurol. 64 (11): 1575–79. 2007. doi:10.1001/archneur.64.11.1575. PMID 17998440.  https://dx.doi.org/10.1001%2Farchneur.64.11.1575
74. "Drugs, Brains, and Behavior: The Science of Addiction". National Institute on Drug Abuse. http://www.drugabuse.gov/publications/science-addiction/drugs-brain. 
75. "Understanding Drug Abuse and Addiction". National Institute on Drug Abuse. November 2012. http://www.drugabuse.gov/infofacts/understand.html. 
76. "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 363 (1507): 3245–55. October 2008. doi:10.1098/rstb.2008.0067. 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607320/table/tbl3/
77. In other words, c-Fos repression allows ΔFosB to more rapidly accumulate within the D1-type medium spiny neurons of the nucleus accumbens because it is selectively induced in this state.[3] Prior to c-Fos repression, all Fos family proteins (e.g., c-Fos, Fra1, Fra2, FosB, and ΔFosB) are induced together, with ΔFosB expression increasing to a lesser extent.[3]
78. According to two medical reviews, ΔFosB has been implicated in causing both increases and decreases in dynorphin expression in different studies;[15][98] this table entry reflects only a decrease.
79. Incentive salience, the "motivational salience" for a reward, is a "desire" or "want" attribute, which includes a motivational component, that the brain assigns to a rewarding stimulus.[99][100] As a consequence, incentive salience acts as a motivational "magnet" for a rewarding stimulus that commands attention, induces approach, and causes the rewarding stimulus to be sought out.[99]
80. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. 2009. pp. 147–48, 366–67, 375–76. ISBN 978-0-07-148127-4. "VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc. ... If motivational drive is described in terms of wanting, and hedonic evaluation in terms of liking, it appears that wanting can be dissociated from liking and that dopamine may influence these phenomena differently. Differences between wanting and liking are confirmed in reports by humans with addictions, who state that their desire for drugs (wanting) increases with continued use even when pleasure (liking) decreases because of tolerance." 
81. "From prediction error to incentive salience: mesolimbic computation of reward motivation". Eur. J. Neurosci. 35 (7): 1124–43. April 2012. doi:10.1111/j.1460-9568.2012.07990.x. PMID 22487042. "Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. ... Associative learning and prediction are important contributors to motivation for rewards. Learning gives incentive value to arbitrary cues such as a Pavlovian conditioned stimulus (CS) that is associated with a reward (unconditioned stimulus or UCS). Learned cues for reward are often potent triggers of desires. For example, learned cues can trigger normal appetites in everyone, and can sometimes trigger compulsive urges and relapse in individuals with addictions.Cue-triggered ‘wanting’ for the UCSA brief CS encounter (or brief UCS encounter) often primes a pulse of elevated motivation to obtain and consume more reward UCS. This is a signature feature of incentive salience.Cue as attractive motivational magnetsWhen a Pavlovian CS+ is attributed with incentive salience it not only triggers ‘wanting’ for its UCS, but often the cue itself becomes highly attractive – even to an irrational degree. This cue attraction is another signature feature of incentive salience ... Two recognizable features of incentive salience are often visible that can be used in neuroscience experiments: (i) UCS-directed ‘wanting’ – CS-triggered pulses of intensified ‘wanting’ for the UCS reward; and (ii) CS-directed ‘wanting’ – motivated attraction to the Pavlovian cue, which makes the arbitrary CS stimulus into a motivational magnet.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3325516
82. Edwards, Scott (2016). "Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder". Neuroscience for Addiction Medicine: From Prevention to Rehabilitation - Constructs and Drugs. Progress in Brain Research. 223. pp. 63–76. doi:10.1016/bs.pbr.2015.07.005. ISBN 978-0-444-63545-7. "An important dimension of reinforcement highly relevant to the addiction process (and particularly relapse) is secondary reinforcement (Stewart, 1992). Secondary reinforcers (in many cases also considered conditioned reinforcers) likely drive the majority of reinforcement processes in humans. In the specific case of drug addition, cues and contexts that are intimately and repeatedly associated with drug use will often themselves become reinforcing ... A fundamental piece of Robinson and Berridge's incentive-sensitization theory of addiction posits that the incentive value or attractive nature of such secondary reinforcement processes, in addition to the primary reinforcers themselves, may persist and even become sensitized over time in league with the development of drug addiction (Robinson and Berridge, 1993)."  https://dx.doi.org/10.1016%2Fbs.pbr.2015.07.005
83. "Pleasure systems in the brain". Neuron 86 (3): 646–64. May 2015. doi:10.1016/j.neuron.2015.02.018. PMID 25950633.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4425246
84. In simplest terms, this means that when either amphetamine or sex is perceived as more alluring or desirable through reward sensitization, this effect occurs with the other as well.
85. "μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacology". Drug Alcohol Depend 121 (3): 173–80. March 2012. doi:10.1016/j.drugalcdep.2011.10.027. PMID 22129844.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3288798
86. "Regulation of chromatin states by drugs of abuse". Curr. Opin. Neurobiol. 30: 112–21. February 2015. doi:10.1016/j.conb.2014.11.002. PMID 25486626. "Studies investigating general HDAC inhibition on behavioral outcomes have produced varying results but it seems that the effects are specific to the timing of exposure (either before, during or after exposure to drugs of abuse) as well as the length of exposure".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4293340
87. "Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health". US Department of Health and Human Services. November 2016. pp. 35–37, 45, 63, 155, 317, 338. https://addiction.surgeongeneral.gov/sites/default/files/surgeon-generals-report.pdf. 
88. "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine 374 (4): 363–371. January 2016. doi:10.1056/NEJMra1511480. PMID 26816013. "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 meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.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 of severe substance-use disorder.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6135257
89. American Psychiatric Association (2013). "Substance-Related and Addictive Disorders". American Psychiatric Publishing. pp. 1–2. http://www.dsm5.org/documents/substance%20use%20disorder%20fact%20sheet.pdf. "Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance." 
90. "An international consensus for assessing internet gaming disorder using the new DSM-5 approach". Addiction 109 (9): 1399–406. September 2014. doi:10.1111/add.12457. PMID 24456155.  https://dx.doi.org/10.1111%2Fadd.12457
91. "Drugs of abuse and brain gene expression". Psychosom Med 61 (5): 630–50. 1999. doi:10.1097/00006842-199909000-00007. PMID 10511013.  https://dx.doi.org/10.1097%2F00006842-199909000-00007
92. "Chapter 16: Reinforcement and Addictive Disorders". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rd ed.). New York: McGraw-Hill Medical. 2015. ISBN 978-0-07-182770-6. "The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2013), which uses the term substance use disorder, is flawed. Criteria used to make the diagnosis of substance use disorders include tolerance and somatic dependence/withdrawal, even though these processes are not integral to addiction as noted. It is ironic and unfortunate that the manual still avoids use of the term addiction as an official diagnosis, even though addiction provides the best description of the clinical syndrome." 
93. "Transforming Diagnosis". National Institute of Mental Health. http://www.nimh.nih.gov/about/director/2013/transforming-diagnosis.shtml. 
94. "Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research" (in en). Drug and Alcohol Dependence 197 (4): 288–298. 2019. doi:10.1016/j.drugalcdep.2019.02.005. PMID 30875650. "Despite this progress, our ability to predict, diagnose, and track addiction in humans based on brain images has been relatively limited. The difficulty elucidating such outcomes may be partly due to a relative dearth of research considering neural white matter, which constitutes over half of human brain volume and plays a vital role in governing communication between cortical areas (Fields, 2008). Diffusion mag- netic resonance imaging has emerged as a method to non-invasively examine white matter in the human brain and relate such connectivity to substance abuse and addictive behaviors (Suckling and Nestor, 2017)".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6440853
95. "The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans". Subst. Abuse Rehabil. 4: 29–43. February 2013. doi:10.2147/SAR.S39684. 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. ... At present, no pharmacological therapy has been approved by the FDA to treat psychostimulant addiction. Many drugs have been tested, but none have shown conclusive efficacy with tolerable side effects in humans.172 ... 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.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3931688
96. Magnusson, D, D (1998). Theoretical Models of Human development. New York: John Wiley & sons. pp. 685–759. 
97. Schlosser, Allison V. (September 2018). "'They Medicated Me Out': Social Flesh and Embodied Citizenship in Addiction Treatment". Contemporary Drug Problems 45 (3): 188–207. doi:10.1177/0091450918781590.  https://dx.doi.org/10.1177%2F0091450918781590
98. Wolfe, Daniel; Saucier, Roxanne (February 2021). "Biotechnologies and the future of opioid addiction treatments". International Journal of Drug Policy 88: 103041. doi:10.1016/j.drugpo.2020.103041. PMID 33246267.  https://dx.doi.org/10.1016%2Fj.drugpo.2020.103041
99. Walter, M.; Dürsteler, K.; Petitjean, S.; Wiesbeck, G.; Euler, S.; Sollberger, D.; Lang, U.; Vogel, M. (20 April 2015). "Psychosoziale Behandlungen bei Suchterkrankungen – Suchtspezifische Psychotherapieformen und ihre Wirksamkeit" (in de). Fortschritte der Neurologie · Psychiatrie 83 (4): 201–210. doi:10.1055/s-0034-1399338. PMID 25893493.  https://dx.doi.org/10.1055%2Fs-0034-1399338
100. "Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments". Front. Psychiatry 6: 175. February 2016. doi:10.3389/fpsyt.2015.00175. PMID 26903885. "Environmental Enrichment ...In humans, non-drug rewards delivered in a contingency management (CM) format successfully reduced drug dependence ... In general, CM programs promote drug abstinence through a combination of positive reinforcement for drug-free urine samples. For instance, voucher-based reinforcement therapy in which medication compliance, therapy session attendance, and negative drug screenings reinforced with vouchers to local business (e.g., movie theater, restaurants, etc.) directly reinforces drug abstinence, provides competing reinforcers, enriches the environment, and it is a robust treatment across a broad range of abused drugs (189). ...Physical ExerciseThere is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction ... In some individuals, exercise has its own rewarding effects, and a behavioral economic interaction may occur, such that physical and social rewards of exercise can substitute for the rewarding effects of drug abuse. ... The value of this form of treatment for drug addiction in laboratory animals and humans is that exercise, if it can substitute for the rewarding effects of drugs, could be self-maintained over an extended period of time. Work to date in [laboratory animals and humans] regarding exercise as a treatment for drug addiction supports this hypothesis. ... However, a RTC study was recently reported by Rawson et al. (226), whereby they used 8 weeks of exercise as a post-residential treatment for METH addiction, showed a significant reduction in use (confirmed by urine screens) in participants who had been using meth 18 days or less a month. ... Animal and human research on physical exercise as a treatment for stimulant addiction indicates that this is one of the most promising treatments on the horizon. [emphasis added]".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4745113
101. "Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis". Neurosci Biobehav Rev 37 (8): 1622–44. September 2013. doi:10.1016/j.neubiorev.2013.06.011. PMID 23806439. "[exercise] efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. ... these data show that exercise can affect dopaminergic signaling at many different levels, which may underlie its ability to modify vulnerability during drug use initiation. Exercise also produces neuroadaptations that may influence an individual's vulnerability to initiate drug use. Consistent with this idea, chronic moderate levels of forced treadmill running blocks not only subsequent methamphetamine-induced conditioned place preference, but also stimulant-induced increases in dopamine release in the NAc (Chen et al., 2008) and striatum (Marques et al., 2008). ... [These] findings indicate the efficacy of exercise at reducing drug intake in drug-dependent individuals ... wheel running [reduces] methamphetamine self-administration under extended access conditions (Engelmann et al., 2013) ... These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuro-adaptive changes that develop during and following extended access to the drug. ... Exercise has been proposed as a treatment for drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes (see Table 4). ... Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3788047
102. "Exercise-based treatments for substance use disorders: evidence, theory, and practicality". Am J Drug Alcohol Abuse 41 (1): 7–15. 2015. doi:10.3109/00952990.2014.976708. PMID 25397661. "The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been published. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4831948
103. "Sex differences in drug addiction and response to exercise intervention: From human to animal studies". Front. Neuroendocrinol. 40: 24–41. July 2015. doi:10.1016/j.yfrne.2015.07.001. PMID 26182835. "Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. ... As briefly reviewed above, a large number of human and rodent studies clearly show that there are sex differences in drug addiction and exercise. The sex differences are also found in the effectiveness of exercise on drug addiction prevention and treatment, as well as underlying neurobiological mechanisms. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation. ... In particular, more studies on the neurobiological mechanism of exercise and its roles in preventing and treating drug addiction are needed.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4712120
104. Sachdeva, Ankur; Choudhary, M; Chandra, M (2015). "Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond". Journal of Clinical and Diagnostic Research 9 (9): VE01–VE07. doi:10.7860/JCDR/2015/13407.6538. PMID 26500991.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4606320
105. "New pharmacological approaches for the treatment of alcoholism". Expert Opinion on Pharmacotherapy 7 (17): 2341–53. December 2006. doi:10.1517/14656566.7.17.2341. PMID 17109610.  https://dx.doi.org/10.1517%2F14656566.7.17.2341
106. "Choosing the right medication for the treatment of alcoholism". Current Psychiatry Reports 8 (5): 383–88. October 2006. doi:10.1007/s11920-006-0040-0. PMID 16968619.  https://dx.doi.org/10.1007%2Fs11920-006-0040-0
107. "Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review". Addiction 99 (7): 811–28. July 2004. doi:10.1111/j.1360-0443.2004.00763.x. PMID 15200577.  https://dx.doi.org/10.1111%2Fj.1360-0443.2004.00763.x
108. "Medications for treating alcohol dependence". American Family Physician 72 (9): 1775–80. November 2005. PMID 16300039.  http://www.ncbi.nlm.nih.gov/pubmed/16300039
109. "Opioid antagonists for alcohol dependence". The Cochrane Database of Systematic Reviews (12): CD001867. December 2010. doi:10.1002/14651858.CD001867.pub2. PMID 21154349.  https://dx.doi.org/10.1002%2F14651858.CD001867.pub2
110. "Cognitive function as an emerging treatment target for marijuana addiction". Exp Clin Psychopharmacol 18 (2): 109–19. April 2010. doi:10.1037/a0019295. PMID 20384422. "Cannabis is the most widely used illicit substance in the world, and demand for effective treatment is increasing. However, abstinence rates following behavioral therapies have been modest, and there are no effective pharmacotherapies for the treatment of cannabis addiction.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2909584
111. "Molecular mechanisms of cannabinoid addiction". Curr. Opin. Neurobiol. 23 (4): 487–92. August 2013. doi:10.1016/j.conb.2013.02.002. PMID 23490548. "14. Nguyen PT, Schmid CL, Raehal KM, Selley DE, Bohn LM, Sim-Selley LJ: b-Arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region dependent manner. Biol Psychiatry 2012, 71:714–24.A pioneering study revealing both positive and negative modulatory effects of beta-arrestin2 on THC tolerance. By demonstrating that tolerance to antinociception is reduced whereas tolerance to catalepsy is enhanced in beta-arrestin2 knockout mice, authors suggest that development of cannabinoid agonists that minimize interactions between CB1Rs and beta-arrestin2 might produce improved cannabinoid analgesics with reduced motor suppression, and be therapeutically beneficial.".  https://dx.doi.org/10.1016%2Fj.conb.2013.02.002
112. "Emerging pharmacotherapies for smoking cessation". Am J Health Syst Pharm 64 (16): 1693–98. 2007. doi:10.2146/ajhp060427. PMID 17687057.  https://dx.doi.org/10.2146%2Fajhp060427
113. Crooks, Peter A.; Bardo, Michael T.; Dwoskin, Linda P. (2014). "Nicotinic Receptor Antagonists as Treatments for Nicotine Abuse". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. 69. pp. 513–551. doi:10.1016/B978-0-12-420118-7.00013-5. ISBN 978-0-12-420118-7.  https://dx.doi.org/10.1016%2FB978-0-12-420118-7.00013-5
114. "A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence". The New England Journal of Medicine 343 (18): 1290–7. November 2000. doi:10.1056/NEJM200011023431802. PMID 11058673.  https://dx.doi.org/10.1056%2FNEJM200011023431802
115. "Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation". Health Technology Assessment 11 (9): 1–171, iii-iv. March 2007. doi:10.3310/hta11090. PMID 17313907.  https://dx.doi.org/10.3310%2Fhta11090
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119. "Pathways into receiving a prescription for diamorphine (heroin) for the treatment of opiate dependence in the United kingdom". European Addiction Research 13 (3): 144–7. 2007. doi:10.1159/000101550. PMID 17570910.  https://dx.doi.org/10.1159%2F000101550
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121. "Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study". BMJ (Clinical Research Ed.) 326 (7396): 959–60. May 2003. doi:10.1136/bmj.326.7396.959. PMID 12727768.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153851
122. "Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research". Expert Rev Clin Pharmacol 7 (3): 363–74. May 2014. doi:10.1586/17512433.2014.909283. PMID 24716825. "Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4017926
123. "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". Cochrane Database Syst. Rev. 9 (9): CD009695. September 2013. doi:10.1002/14651858.CD009695.pub2. PMID 23996457. "To date, no pharmacological treatment has been approved for [addiction], and psychotherapy remains the mainstay of treatment. ... Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy".  https://dx.doi.org/10.1002%2F14651858.CD009695.pub2
124. "Future pharmacological treatments for substance use disorders". Br. J. Clin. Pharmacol. 77 (2): 382–400. February 2014. doi:10.1111/j.1365-2125.2012.04474.x. PMID 23039267.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4014020
125. ""TAARgeting Addiction" – The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. February 2016. doi:10.1016/j.drugalcdep.2015.11.014. PMID 26644139. "When considered together with the rapidly growing literature in the field a compelling case emerges in support of developing TAAR1-selective agonists as medications for preventing relapse to psychostimulant abuse.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4724540
126. "Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction". Eur. J. Pharmacol. 761: 345–52. August 2015. doi:10.1016/j.ejphar.2015.06.019. PMID 26092759. "Taken together, the data reviewed here strongly support that TAAR1 is implicated in the functional regulation of monoaminergic systems, especially dopaminergic system, and that TAAR1 serves as a homeostatic "brake" system that is involved in the modulation of dopaminergic activity. Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction. ... Given that TAAR1 is primarily located in the intracellular compartments and existing TAAR1 agonists are proposed to get access to the receptors by translocation to the cell interior (Miller, 2011), future drug design and development efforts may need to take strategies of drug delivery into consideration (Rajendran et al., 2010).".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4532615
127. "Drug addiction: a curable mental disorder?". Acta Pharmacologica Sinica 39 (12): 1823–1829. December 2018. doi:10.1038/s41401-018-0180-x. PMID 30382181.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6289334
128. "Is immunotherapy an opportunity for effective treatment of drug addiction?". Vaccine 33 (48): 6545–51. November 2015. doi:10.1016/j.vaccine.2015.09.079. PMID 26432911.  https://dx.doi.org/10.1016%2Fj.vaccine.2015.09.079
129. "The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse". J. Immunol. 194 (12): 5926–36. June 2015. doi:10.4049/jimmunol.1500385. PMID 25972483. "Translation of therapeutic vaccines for addiction, cancer, or other chronic noncommunicable diseases has been slow because only a small subset of immunized subjects achieved effective Ab levels.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4458396
130. Painter A. (2019) "Researchers working to develop vaccines to fight opioid addiction" Vtnews.vt.edu https://vtnews.vt.edu/articles/2019/09/cals-mikezhang.html
131. "Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction". Eur. J. Pharmacol. 780: 129–35. March 2016. doi:10.1016/j.ejphar.2016.03.040. PMID 27018393.  https://dx.doi.org/10.1016%2Fj.ejphar.2016.03.040
132. "Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity". Neurosci Biobehav Rev 61: 35–52. February 2016. doi:10.1016/j.neubiorev.2015.11.010. PMID 26657968.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4731270
133. "[GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators]" (in pl). Psychiatr. Pol. 49 (2): 215–23. April 2015. doi:10.12740/PP/33911. PMID 26093587.  https://dx.doi.org/10.12740%2FPP%2F33911
134. "GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators". Neuropharmacology 88: 36–47. January 2015. doi:10.1016/j.neuropharm.2014.06.016. PMID 24971600.  https://dx.doi.org/10.1016%2Fj.neuropharm.2014.06.016
135. Inhibitors of class I histone deacetylase (HDAC) enzymes are drugs that inhibit four specific histone-modifying enzymes: HDAC1, HDAC2, HDAC3, and HDAC8. Most of the animal research with HDAC inhibitors has been conducted with four drugs: butyrate salts (mainly sodium butyrate), trichostatin A, valproic acid, and SAHA;[148][104] butyric acid is a naturally occurring short-chain fatty acid in humans, while the latter two compounds are FDA-approved drugs with medical indications unrelated to addiction.
136. "The Epigenetic Mechanisms of Amphetamine". J. Addict. Prev. 2015 (Suppl 1). February 2015. PMID 27453897. "Epigenetic modifications caused by addictive drugs play an important role in neuronal plasticity and in drug-induced behavioral responses. Although few studies have investigated the effects of AMPH on gene regulation (Table 1), current data suggest that AMPH acts at multiple levels to alter histone/DNA interaction and to recruit transcription factors which ultimately cause repression of some genes and activation of other genes. Importantly, some studies have also correlated the epigenetic regulation induced by AMPH with the behavioral outcomes caused by this drug, suggesting therefore that epigenetics remodeling underlies the behavioral changes induced by AMPH. If this proves to be true, the use of specific drugs that inhibit histone acetylation, methylation or DNA methylation might be an important therapeutic alternative to prevent and/or reverse AMPH addiction and mitigate the side effects generate by AMPH when used to treat ADHD.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4955852
137. Specifically, prolonged administration of a class I HDAC inhibitor appears to reduce an animal's motivation to acquire and use an addictive drug without affecting an animals motivation to attain other rewards (i.e., it does not appear to cause motivational anhedonia) and reduce the amount of the drug that is self-administered when it is readily available.[81][104][149]
138. Primary references involving sodium butyrate: • "Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation". Nat. Neurosci. 16 (4): 434–40. April 2013. doi:10.1038/nn.3354. PMID 23475113. "While acute HDAC inhibition enhances the behavioral effects of cocaine or amphetamine1,3,4,13,14, studies suggest that more chronic regimens block psychostimulant-induced plasticity3,5,11,12. ... The effects of pharmacological inhibition of HDACs on psychostimulant-induced plasticity appear to depend on the timecourse of HDAC inhibition. Studies employing co-administration procedures in which inhibitors are given acutely, just prior to psychostimulant administration, report heightened behavioral responses to the drug1,3,4,13,14. In contrast, experimental paradigms like the one employed here, in which HDAC inhibitors are administered more chronically, for several days prior to psychostimulant exposure, show inhibited expression3 or decreased acquisition of behavioral adaptations to drug5,11,12. The clustering of seemingly discrepant results based on experimental methodologies is interesting in light of our present findings. Both HDAC inhibitors and psychostimulants increase global levels of histone acetylation in NAc. Thus, when co-administered acutely, these drugs may have synergistic effects, leading to heightened transcriptional activation of psychostimulant-regulated target genes. In contrast, when a psychostimulant is given in the context of prolonged, HDAC inhibitor-induced hyperacetylation, homeostatic processes may direct AcH3 binding to the promoters of genes (e.g., G9a) responsible for inducing chromatin condensation and gene repression (e.g., via H3K9me2) in order to dampen already heightened transcriptional activation. Our present findings thus demonstrate clear cross talk among histone PTMs and suggest that decreased behavioral sensitivity to psychostimulants following prolonged HDAC inhibition might be mediated through decreased activity of HDAC1 at H3K9 KMT promoters and subsequent increases in H3K9me2 and gene repression.".  • "The histone deacetylase inhibitor sodium butyrate decreases excessive ethanol intake in dependent animals". Addict Biol 20 (4): 676–89. July 2015. doi:10.1111/adb.12161. PMID 25041570. "Altogether, our results clearly demonstrated the efficacy of NaB in preventing excessive ethanol intake and relapse and support the hypothesis that HDACi may have a potential use in alcohol addiction treatment.".  • "Inhibition of histone deacetylases facilitates extinction and attenuates reinstatement of nicotine self-administration in rats". PLOS ONE 10 (4): e0124796. April 2015. doi:10.1371/journal.pone.0124796. PMID 25880762. Bibcode: 2015PLoSO..1024796C. "treatment with NaB significantly attenuated nicotine and nicotine + cue reinstatement when administered immediately ... These results provide the first demonstration that HDAC inhibition facilitates the extinction of responding for an intravenously self-administered drug of abuse and further highlight the potential of HDAC inhibitors in the treatment of drug addiction.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3609040
139. "Molecular mechanisms of synaptic remodeling in alcoholism". Neurosci. Lett. 601: 11–19. August 2015. doi:10.1016/j.neulet.2015.01.051. PMID 25623036. "Increased HDAC2 expression decreases the expression of genes important for the maintenance of dendritic spine density such as BDNF, Arc, and NPY, leading to increased anxiety and alcohol-seeking behavior. Decreasing HDAC2 reverses both the molecular and behavioral consequences of alcohol addiction, thus implicating this enzyme as a potential treatment target (Fig. 3). HDAC2 is also crucial for the induction and maintenance of structural synaptic plasticity in other neurological domains such as memory formation [115]. Taken together, these findings underscore the potential usefulness of HDAC inhibition in treating alcohol use disorders ... Given the ability of HDAC inhibitors to potently modulate the synaptic plasticity of learning and memory [118], these drugs hold potential as treatment for substance abuse-related disorders. ... Our lab and others have published extensively on the ability of HDAC inhibitors to reverse the gene expression deficits caused by multiple models of alcoholism and alcohol abuse, the results of which were discussed above [25,112,113]. This data supports further examination of histone modifying agents as potential therapeutic drugs in the treatment of alcohol addiction ... Future studies should continue to elucidate the specific epigenetic mechanisms underlying compulsive alcohol use and alcoholism, as this is likely to provide new molecular targets for clinical intervention.".  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4506731
140. Among the few clinical trials that employed a class I HDAC inhibitor, one utilized valproate for methamphetamine addiction.[151]
141. "Gene Therapy For Addiction: Flooding Brain With 'Pleasure Chemical' Receptors Works On Cocaine, As On Alcohol". https://www.sciencedaily.com/releases/2008/04/080416081628.htm. 
142. "Gene Transfer Therapy for Cocaine Addiction Passes Tests in Animals". National Institute on Drug Abuse. 14 January 2016. https://www.drugabuse.gov/news-events/nida-notes/2016/01/gene-transfer-therapy-cocaine-addiction-passes-tests-in-animals. 
143. "Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice". Vaccine 32 (33): 4155–62. 2014. doi:10.1016/j.vaccine.2014.05.067. PMID 24892251.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4077905
144. "Using Adeno-Associated Virus (AAV) Mediated Sustained Expression of an Anti-methamphetamine Antibody Fragment to Alter Methamphetamine Disposition in Mice". http://abstracts.aaps.org/Verify/AAPS2014/PosterSubmissions/T3009.pdf. 
145. "ATTC – Addiction Science Made Easy". http://www.attcnetwork.org/explore/priorityareas/science/tools/asmeDetails.asp?ID=69. 
146. Chen, Chiao-Chicy; Yin, Shih-Jiun (January 2008). "Alcohol abuse and related factors in Asia". International Review of Psychiatry 20 (5): 425–433. doi:10.1080/09540260802344075. PMID 19012127.  https://dx.doi.org/10.1080%2F09540260802344075
147. Mak, Kwok-Kei; Lai, Ching-Man; Watanabe, Hiroko; Kim, Dong-Il; Bahar, Norharlina; Ramos, Milen; Young, Kimberly S.; Ho, Roger C.M. et al. (November 2014). "Epidemiology of Internet Behaviors and Addiction Among Adolescents in Six Asian Countries". Cyberpsychology, Behavior, and Social Networking 17 (11): 720–728. doi:10.1089/cyber.2014.0139. PMID 25405785.  https://dx.doi.org/10.1089%2Fcyber.2014.0139
148. "The Mental Health of Australians 2: Substance Use Disorders in Australia". Department of Health and Ageing, Canberra. May 2009. https://www.health.gov.au/internet/main/publishing.nsf/Content/A24556C814804A99CA257BF0001CAC45/$File/mha26.pdf. 
149. Peacock, Amy; Leung, Janni; Larney, Sarah; Colledge, Samantha; Hickman, Matthew; Rehm, Jürgen; Giovino, Gary A.; West, Robert et al. (October 2018). "Global statistics on alcohol, tobacco and illicit drug use: 2017 status report". Addiction 113 (10): 1905–1926. doi:10.1111/add.14234. PMID 29749059.  https://dx.doi.org/10.1111%2Fadd.14234
150. The lifetime prevalence of an addiction is the percentage of individuals in a population that developed an addiction at some point in their life.
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153. "American Board of Medical Specialties recognizes the new subspecialty of addiction medicine". 14 March 2016. http://www.abam.net/wp-content/uploads/2016/03/1.-News-Release-ADM.pdf. "Sixteen percent of the non-institutionalized U.S. population age 12 and over – more than 40 million Americans – meets medical criteria for addiction involving nicotine, alcohol or other drugs. This is more than the number of Americans with cancer, diabetes or heart conditions. In 2014, 22.5 million people in the United States needed treatment for addiction involving alcohol or drugs other than nicotine, but only 11.6 percent received any form of inpatient, residential, or outpatient treatment. Of those who do receive treatment, few receive evidence-based care. (There is no information available on how many individuals receive treatment for addiction involving nicotine.)Risky substance use and untreated addiction account for one-third of inpatient hospital costs and 20 percent of all deaths in the United States each year, and cause or contribute to more than 100 other conditions requiring medical care, as well as vehicular crashes, other fatal and non-fatal injuries, overdose deaths, suicides, homicides, domestic discord, the highest incarceration rate in the world and many other costly social consequences. The economic cost to society is greater than the cost of diabetes and all cancers combined. Despite these startling statistics on the prevalence and costs of addiction, few physicians have been trained to prevent or treat it." 
154. "A Major Step Forward for Addiction Medicine". National Institutes of Health. 31 March 2016. https://www.drugabuse.gov/about-nida/noras-blog/2016/03/major-step-forward-addiction-medicine. "Only about 10 percent of the 21 million Americans who meet the need for care for an alcohol or drug use disorder receive any form of treatment, and much of the treatment available does not meet standards for evidence-based care. There are many attitudinal and systemic reasons for this treatment gap, including stigma against treating people with addictions and institutional barriers to providing or funding addiction treatment. ... A major milestone was reached on March 14, 2016, when the American Board of Medical Specialties (ABMS) formally announced recognition of the field of Addiction Medicine as a medical subspecialty. ... In a statement issued to mark this milestone, ABAM President Robert J. Sokol summed up its significance: 'This landmark event, more than any other, recognizes addiction as a preventable and treatable disease, helping to shed the stigma that has long plagued it. It sends a strong message to the public that American medicine is committed to providing expert care for this disease and services designed to prevent the risky substance use that precedes it.'" 
155. "Nearly half of Americans have a family member or close friend who's been addicted to drugs". Pew Research Center. 26 October 2017. http://www.pewresearch.org/fact-tank/2017/10/26/nearly-half-of-americans-have-a-family-member-or-close-friend-whos-been-addicted-to-drugs/. 
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157. World Drug Report 2012. United Nations. June 2012. ISBN 978-92-1-148267-6. https://www.unodc.org/documents/data-and-analysis/WDR2012/WDR_2012_web_small.pdf. 
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160. "The role of affective dysregulation in drug addiction". Clin Psychol Rev 30 (6): 621–34. August 2010. doi:10.1016/j.cpr.2010.04.005. PMID 20546986.  https://dx.doi.org/10.1016%2Fj.cpr.2010.04.005
161. "BIS/BAS personality characteristics and college students' substance use". Personality and Individual Differences 40 (7): 1497–503. 2006. doi:10.1016/j.paid.2005.12.005.  https://dx.doi.org/10.1016%2Fj.paid.2005.12.005
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166. Online Etymology Dictionary : alcohol http://www.etymonline.com/index.php?search=alcohol&searchmode=none
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