Review Article

From the Neurobiologic Basis of Alcohol Dependency to Pharmacologic Treatment Strategies: Bridging the Knowledge Gap

Authors: Christopher W. Shea, MA, CRAT, CAC-AD

Abstract

Alcohol dependence (AD) is a complex disease involving biologic, psychosocial, and environmental factors. Increasing evidence shows that the development of AD involves changes in neurotransmitter function in the areas of the brain associated with alcohol craving and reward. Although AD is gaining acceptance as a medical disease, management of AD rarely includes medical treatment. Pharmacotherapy is a useful adjunct to psychosocial therapy and can target the biologic changes associated with AD. Similar to the role of medications in depression, pharmacotherapy can improve the response to psychosocial therapy and should thus be initiated early in the course of treatment. By reducing cravings and alcohol-associated rewards, pharmacotherapy can reduce heavy drinking days, increase abstinence, and help patients focus on their treatment goals. Pharmacotherapy represents a valuable component of treatment and should be combined with psychosocial and behavioral interventions to address the multifactorial nature of AD in individuals with this disease.


Key Points


* Alcohol dependency is a disease, but treatment traditionally has focused almost exclusively on psychosocial intervention.


* Recent studies indicate alcohol abuse has a neurobiologic component that can be managed effectively with appropriate pharmacotherapy.


* Pharmacologic treatment, used in conjunction with psychosocial approaches, is an important part of an effective treatment plan for alcohol dependency.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. US Department of Health and Human Services: National Survey on Drug Use and Health Report: alcohol dependence or abuse: 2002, 2003, and 2004. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2006:16, 1–4.
 
2. Harwood HJ. US Department of Health and Human Services: updating estimates of the economic costs of alcohol abuse in the United States: estimates, update methods and data. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2000, pp 1–17.
 
3. Jung YC, Namkoong K. Pharmacotherapy for alcohol dependence: anticraving medications for relapse prevention. Yonsei Med J 2006;47:167–178.
 
4. Kranzler HR. Pharmacotherapy of alcoholism: gaps in knowledge and opportunities for research. Alcohol Alcohol 2000;35:537–547.
 
5. The National Center on Addiction and Substance Abuse: missed opportunity: national survey of primary care physicians and patients on substance abuse. New York, NY: The National Center on Addiction and Substance Abuse at Columbia University; 2000. pp i–v.
 
6. Wyatt SA, Vilensky W, Manlandro JJ, et al. Medical education in substance abuse: from student to practicing osteopathic physician. J Am Osteopath Assoc 2005;105:S18–S25.
 
7. Giannetti VJ, Sieppert JD, Holosko MJ. Attitudes and knowledge concerning alcohol abuse: curriculum implications. J Health Soc Policy 2002;15:45–58.
 
8. Robinson TE, Berridge KC. Addiction. Annu Rev Psychol 2003;54:25–53.
 
9. Weiss F, Porrino LJ. Behavioral neurobiology of alcohol addiction: recent advances and challenges. J Neurosci 2002;22:3332–3337.
 
10. Dick DM, Bierut LJ. The genetics of alcohol dependence. Curr Psychiatry Rep 2006;8:151–157.
 
11. Brodie MS, Shefner SA, Dunwiddie TV. Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 1990;508:65–69.
 
12. Yim HJ, Gonzales RA. Ethanol-induced increases in dopamine extracellular concentration in rat nucleus accumbens are accounted for by increased release and not uptake inhibition. Alcohol 2000;22:107–115.
 
13. Risinger FO, Freeman PA, Rubinstein M, et al. Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Psychopharmacology (Berl) 2000;152:343–350.
 
14. Cunningham CL, Howard MA, Gill SJ, et al. Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice. Pharmacol Biochem Behav 2000;67:693–699.
 
15. El-Ghundi M, George SR, Drago J, et al. Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior. Eur J Pharmacol 1998;353:149–158.
 
16. Jamensky NT, Gianoulakis C. Content of dynorphins and κ-opioid receptors in distinct brain regions of C57BL/6 and DBA/2 mice. Alcohol Clin Exp Res 1997;21:1455–1464.
 
17. Benjamin D, Grant ER, Pohorecky LA. Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats. Brain Res 1993;621:137–140.
 
18. Garbutt JC, Kranzler HR, O’Malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA 2005;293:1617–1625.
 
19. Volpicelli JR, Alterman AI, Hayashida M, et al. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 1992;49:876–880.
 
20. Grobin AC, Matthews DB, Devaud LL, et al. The role of GABAA receptors in the acute and chronic effects of ethanol. Psychopharmacology (Berl) 1998;139:2–19.
 
21. Gorski TT. The Gorski-CENAPS model: an overview: science based approach. Independence, MO: Herald House Independence Press; 1997, pp 1–58.
 
22. Dawson DA, Grant BF, Stinson FS, et al. Recovery from DSM-IV alcohol dependence: United States, 2001-2002. Addiction 2005;100:281–292.
23. Moos RH, Moos BS. Rates and predictors of relapse after natural and treated remission from alcohol use disorders. Addiction 2006;101:212–222.
 
24. Miller WR, Harris RJ. A simple scale of Gorski’s warning signs for relapse. J Stud Alcohol 2000;61:759–765.
 
25. Heinz A, Reimold M, Wrase J, et al. Correlation of stable elevations in striatal μ-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 2005;62:57–64.
 
26. Heinz A, Siessmeier T, Wrase J, et al. Correlation between dopamine D2 receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 2004;161:1783–1789.
 
27. Volkow ND, Wang GJ, Fowler JS, et al. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 1996;20:1594–1598.
 
28. Heinz A, Siessmeier T, Wrase J, et al. Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients. Am J Psychiatry 2005;162:1515–1520.
 
29. Braus DF, Wrase J, Grüsser S, et al. Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics. J Neural Transm 2001;108:887–894.
 
30. Tiffany ST. Cognitive concepts of craving. Alcohol Res Health 1999;23:215–224.
 
31. George MS, Anton RF, Bloomer C, et al. Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch Gen Psychiatry 2001;58:345–352.
 
32. Myrick H, Anton RF, Li X, et al. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology 2004;29:393–402.
 
33. US Department of Health and Human Services: helping patients who drink too much: a clinician’s guide. Rockville, MD: National Institute on Drug Abuse and Alcoholism; 2005, pp 1–31.
 
34. Rosenthal RN. Intramuscular naltrexone: targeting adherence in alcohol dependency treatment. Curr Psychiatry 2006;5:106–111.
 
35. Mason BJ, Goodman AM, Chabac S, et al. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res 2006;40:383–393.
 
36. Williams SH. Medications for treating alcohol dependence. Am Fam Physician 2005;72:1775–1780.
 
37. Fuller RK, Branchey L, Brightwell DR, et al. Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA 1986;256:1449–1455.
 
38. Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study. JAMA 2006;295:2003–2017.
 
39. Gianoulakis C. Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. J Psychiatry Neurosci 2001;26:304–318.
 
40. National Institute on Drug Abuse: NIDA notes: the brain’s drug reward system. Rockville, MD: National Institutes of Health; 1996. Available at: http://www.nida.nih.gov/NIDA_Notes/NNVol11N4/Brain.html. Accessed October 10, 2006.