Abstract
The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.
A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug’s original indication by the FDA. Such ‘off-label’ prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature.
The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect.
Similar content being viewed by others
Notes
Although the abbreviation SUD is used in this review, the term technically includes drug intoxication and withdrawal. This review addresses only the pharmacotherapy of substance abuse and dependence.
References
Substance Abuse and Mental Health Services Administration (SAMHSA). National survey on drug use and health, 2004 [online]. Available from URL: http://www.drugabusestatistics.samhsa.gov/products.htm [Accessed 2005 Oct 3]
Substance Abuse and Mental Health Services Administration (SAMHSA). The Treatment Episode Data Set (TEDS) report, highlights: 2004. National admissions to substance abuse treatment services [online]. Available from URL: http://wwwdasis.samhsa.gov/teds04/tedshigh2k4.pdf [Accessed 2006 May 13]
Substance Abuse and Mental Health Services Administration (SAMHSA). Polydrug Admissions: 2002. The Drug and Alcohol Services Information System Report, March 2005 [online]. Available from URL: http://drugabusestatistics.samhsa.gov/2k5/polydrugTX/polydrugTX.htm [Accessed 2005 Oct 3]
Kosten, TR. Client issues in drug abuse treatment: addressing multiple drug abuse. National Institute on Drug Abuse research monograph no. 106, 1991. Improving drug abuse treatment: 136-151 [online]. Available from URL: http://www.drugabuse.gov/pdf/monographs/106.pdf [Accessed 2005 Nov 9]
Baigent MF. Physical complications of substance abuse: what psychiatrists need to know. Curr Opin Psychiatry 2003; 16(3): 291–6
Stein MD. Medical consequences of substance abuse. Psychiatr Clin North Am 1999; 22(2): 351–70
Iguchi MY, Handelsman L, Bickel WK, et al. Benzodiazepine and sedative use/abuse by methadone maintenance clients. Drug Alcohol Depend 1993; 32(3): 257–66
Tizabi Y, Copeland RL, Louis VA, et al. Effects of combined systemic alcohol and central nicotine administration into ventral tegmental area on dopamine release in the nucleus accumbens. Alcohol Clin Exp Res 2002; 26(3): 394–9
Raven MA, Necessary BD, Danluck DA, et al. Comparison of the reinforcing and anxiogenic effects of intravenous cocaine and cocaethylene. Exp Clinical Psychopharm 2000; 8(1): 117–24
Ciraulo D, Shader R, Greenblatt D, et al. Drug interactions in psychiatry. 3rd ed. New York: Lippincott, Williams and Wilkins, 2006
Lingford-Hughes AR, Welch S, Nutt DJ. Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology. J Psychopharm 2004; 8(3): 293–335
American Psychiatric Association. Practice guideline for the treatment of patients with substance use disorders. 2nd ed. New York: American Psychiatric Press, 2006
Maldonado R, Valverde O, Berrendero F. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 2006; 29(4): 225–32
Volkow ND, Wang GJ, Fischman MW, et al. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 1997; 386(6627): 827–30
Nestler E. Is there a common molecular pathway for addiction? Nat Neuroscience 2005; 8(11): 1445–9
Johnson BA. Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 2005; 19(10): 873–96
Kiefer F, Jahn H, Tarnaske T, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2003; 60(1): 92–9
Tennant F, Shannon J. Cocaine abuse in methadone maintenance patients is associated with low serum methadone concentrations. J Addict Dis 1995; 14(1): 67–74
Substance Abuse and Mental Health Services Administration. Results from the 2004 national survey on drug use and health: national findings [online]. Available from URL: http://www.Oas.samhsa.gov/nsduh/2k4nsduh/2k4results/2k4results.pdf [Access 2007 Feb 13]
Haney M. The marijuana withdrawal syndrome: diagnosis and treatment. Curr Psychiatry Rep 2005; 7(5): 360–6
McRae AL, Budney AJ, Brady KT. Treatment of marijuana dependence: a review of the literature. J Subst Abuse Treat 2003; 24(4): 369–76
Hart CL. Increasing treatment options for cannabis dependence: a review of potential pharmacotherapies. Drug Alcohol Depend 2005; 80(2): 147–59
Levin FR, McDowell D, Evans SM, et al. Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict 2004; 13(1): 21–32
Biberman R, Neumann R, Katzir I, et al. A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation. Addiction 2003; 98(10): 1403–7
Moore BA. Selegiline for treatment of cannabis dependence [online]. Available from URL: http://www.crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6952443&p_grant_num=5R21DA019246-02&p_query=(selegiline+%26+marijuana)&ticket=30797689&p_audit_session_id=200664101&p_audit_score=12&p_audit_numfound=1&p_keywords=selegiline+marijuana [Accessed 2006 Jan 7]
Penetar DM. Bupropion effects on marijuana withdrawal symptoms [online]. Available from URL: http://www.crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6952786&p_ grant_num=5R03DA017275-02&p_query=(bupropion+%26 +marijuana)&ticket=30797741&p_audit_session_id=2006 64101&p_audit_score=23&p_audit_numfound=l&p_ keywords=bupropion+marijuana [Accessed 2006 Jan 7]
Heidbreder CA, Hagan JJ. Novel pharmacotherapeutic approaches for the treatment of drug addiction and craving. Curr Opin Pharmacol 2005; 5(1): 107–18
Kreek MJ, LaForge KS, Butelman E. Pharmacotherapy of addictions. Nat Rev Drug Discov 2002; 1(9): 710–26
Sanchis-Segura C, Grisel JE, Olive MF, et al. Role of the endogenous opioid system on the neuropsychopharmacological effects of ethanol: new insights about an old question. Alcohol Clin Exp Res 2005; 29(8): 1522–7
Paul SM. Alcohol-sensitive GABA receptors and alcohol antagonists. Proc Natl Acad Sci U S A 2006; 103(22): 8307–8
Mihic SJ, Harris RA. GABA and the GABAA receptor. Alcohol Res World 1997; 2: 127–31
Tsai G, Gastfriend DR, Coyle JT. The glutamatergic basis of human alcoholism. Am J Psychiatry 1995; 152: 332–40
Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005; 162(8): 1403–13
Laizure SC, Mandrell T, Gades NM, et al. Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases. Drug Met Dist 2003; 31(1): 16–20
Kreek MJ, Bart G, Lilly C, et al. Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Pharmacol Rev 2005; 57(1): 1–26
Siggins GR, Martin G, Roberto M, et al. Glutamatergic transmission in opiate and alcohol dependence. Ann N Y Acad Sci 2003; 1003: 196–211
Ait-Daoud N, Wiesbeck GA, Bienkowski P, et al. Comorbid alcohol and nicotine dependence: from the biomolecular basis to clinical consequences. Alcohol Clin Exp Res 2005; 29(8): 1541–9
Madden PA, Bucholz KK, Martin NG, et al. Smoking and the genetic contribution to alcohol-dependence risk. Alcohol Res Health 2000; 24: 209–14
Goldman D, Bergen A. General and specific inheritance of substance abuse and alcoholism. Arch Gen Psychiatry 1998; 55: 964–5
Radel M, Goldman D. Pharmacogenetics of alcohol response and alcoholism: the interplay of genes and environmental factors in thresholds for alcoholism. Drug Metab Disp 2001; 29 (4 Pt 2): 489–94
Howard LA, Miksys S, Hoffmann E, et al. Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics. Br J Pharmacol 2003; 138(7): 1376–86
Tizabi Y, Louis VA, Taylor CT, et al. Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder. Biol Psychiatry 2002; 51(2): 164–71
Blomqvist O, Ericson M, Johnson DH, et al. Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. Eur J Pharmacol 1986; 314: 257–67
Blomqvist O, Ericson M, Engel JA, et al. Accumbal dopamine overflow after ethanol: localization of the antagonizing effect of mecamylamine. Eur J Pharmacol 1997; 334: 149–56
Ericson M, Blomqvist O, Engel JA, et al. Voluntary ethanol intake in the rat and the associated accumbal dopamine overflow are blocked by ventral tegmental mecamylamine. Eur J Pharmacol 1998; 358: 189–96
Le AD, Wang A, Harding S, et al. Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats. Psychopharmacol 2003; 168(1–2): 216–21
Hughes J, Kaiman D. Do smokers with alcohol problems have more difficulty quitting? Drug Alcohol Depend 2005; 82(2): 91–102
Barrett SP, Tichauer M, Leyton M, et al. Nicotine increases alcohol self-administration in non-dependent male smokers. Drug Alcohol Depend 2006; 81(2): 197–204
King AC, Epstein AM. Alcohol dose-dependent increases in smoking urge in light smokers. Alcohol Clin Exp Res 2005; 29(4): 547–52
Tizabi Y, Manaye KF, Smoot DT, et al. Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Neurotox Res 2004; 6(4): 311–6
Dole VP. Implications of methadone maintenance for theories of narcotic addiction. JAMA 1988; 260(20): 3025–9
Gearing FR, Schweitzer MD. An epidemiologic evaluation of long-term methadone maintenance treatment for heroin addiction. Am J Epidemiol 1974; 100(2): 101–12
Payte JT. A brief history of methadone in the treatment of opioid dependence: a personal perspective. J Psychoactive Drugs 1991; 23(2): 103–7
Zweben JE, Payte JT. Methadone maintenance in the treatment of opioid dependence: a current perspective. West J Med 1990; 152(5): 588–99
Stine SM. Methadone treatment for opioid dependence. J Nervous Mental Dis 2001; 189(1): 65–6
Appel PW, Joseph H, Richman BL. Causes and rates of death among methadone maintenance patients before and after the onset of the HIV/AIDS epidemic. Mt Sinai J Med 2000; 67(5–6): 444–51
Backmund M, Meyer K, Von Zielonka M, et al. Treatment of hepatitis C infection in injection drug users. Hepatology 2001; 34(1): 188–93
Bell J, Zador D. A risk-benefit analysis of methadone maintenance treatment. Drug Saf 2000; 22(3): 179–90
Goldstein A, Herrera J. Heroin addicts and methadone treatment in Albuquerque: a 22-year follow-up. Drug Alcohol Depend 1995; 40(2): 139–50
Concool B, Smith H, Stimmel B. Mortality rates of persons entering methadone maintenance: a seven-year study. Am J Drug Alcohol Abuse 1979; 6(3): 345–53
Kreek MJ, Dodes L, Kane S, et al. Long-term methadone maintenance therapy: effects on liver function. Ann Intern Med 1972; 77(4): 598–602
Maxwell JC, Pullum TW, Tannert K. Deaths of clients in methadone treatment in Texas: 1994–2002. Drug Alcohol Depend 2005; 78(1): 73–81
Kreek MJ. Opiate-ethanol interactions: implications for the biological basis and treatment of combined addictive diseases. NIDA Res Monogr 1988; 81: 428–39
Novick DM, Enlow RW, Gelb AM, et al. Hepatic cirrhosis in young adults: association with adolescent onset of alcohol and parenteral heroin abuse. Gut 1995; 26: 8–13
Foster DJ, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol 1999; 47(4): 403–12
Beverley CL, Kreek MJ, Wells AO, et al. Effects of alcohol abuse on progression of liver disease in methadone-maintained patients. NIDA Res Monograph 1979; 27: 399–401
Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet 2002; 41(14): 1153–93
Bencherif B, Wand GS, McCaul ME, et al. Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry 2004; 55(3): 255–62
Karch SB, Stephens BG. Toxicology and pathology of deaths related to methadone: retrospective review. West J Med 2000; 172(1): 11–4
Caplehorn JR, Dalton MS, Haldar F, et al. Methadone maintenance and addicts’ risk of fatal heroin overdose. Subst Use Misuse 1996; 31(2): 177–96
Harding-Pink D. Deaths associated with methadone. J Toxicol Clin Exp 1991; 11(1): 31–49
Davoli M, Perucci CA, Forastiere F, et al. Risk factors for overdose mortality: a case-control study within a cohort of intravenous drug users. Int J Epidemiol 1993; 22(2): 273–7
Borron SW, Monier C, Risede P, et al. Interaction of opiates with benzodiazepines in overdoses [letter]. J Toxicol Clin Toxicol 2001; 39(3): 212
Haberman PW, Noble JA, Dufour MC. Alcohol use in combination with cocaine, heroin and methadone by medical examiner cases. J Stud Alcohol 1995; 56(3): 344–7
Substance Abuse and Mental Health Services Administration (SAMHSA). Mortality data from the drug abuse warning network, 2001 [online]. Available from URL: https://dawninfo.samhsa.gov/old_dawn/pubs_94_02/mepubs/files/DAWN2001/DAWN2001_ME_A.pdf [Accessed 2005 Oct 3]
Stimmel B, Hanbury R, Sturiano V, et al. Alcoholism as a risk factor in methadone maintenance: a randomized controlled trial. Am J Med 1982; 73(5): 631–6
Kramer T. Side effects and therapeutic effects. Medscape Gen Med 2003; 5 (1) [online]. Available from URL: https://www.medscape.com/viewarticle/448250 [Accessed 2005 Oct 5]
Jackson G, Cohen M, Hanbury R, et al. Alcoholism among narcotic addicts and patients on methadone maintenance. J Stud Alcohol 1983; 44(3): 499–504
Rounsaville BJ, Weissman MM, Wilber C, et al. Identifying alcoholism in treated opiate addicts. Am J Psychiatry 1983; 140(6): 764–6
Ottomanelli G. Methadone patients and alcohol abuse. J Subst Abuse Treat 1999; 16(2): 113–21
Nagy J. Renaissance of NMDA receptor antagonists: do they have a role in the pharmacotherapy for alcoholism? IDrugs 2004; 7(4): 339–50
Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 1999; 251: 85–7
Bisaga A, Evans SM. Acute effects of memantine in combination with alcohol in moderate drinkers. Psychopharmacology 2004; 172(1): 16–24
O’Malley SS, Jaffe AJ, Chang G, et al. Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 1992; 49(11): 881–7
Bisaga A, Comer SD, Ward AS, et al. The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans. Psychopharmacology 2001; 157(1): 1–10
Sullivan MA, Rothenberg JL, Vosburg SK, et al. Predictors of retention in naltrexone maintenance for opioid dependence: analysis of a stage I trial. Am J Addict 2006; 15(2): 150–9
Bisaga A. Memantine naltrexone treatment for opioid dependence [online]. Available from URL: http://www.crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6823375&p_ grant_num=1R01DA015822-01A2&p_query=(memantine+ %26+methadone)&ticket=30797788&p_audit_session_id= 200664101&p_audit_score=11&p_audit_numfound=1&p_ keywords=memantine+methadone [Accessed 2005 Oct 26]
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(5): 383–93
Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006; 295(17): 2003–17
Sass H, Soyka M, Mann K, et al. Relapse prevention by acamprosate: results from a placebo controlled study on alcohol dependence. Arch Gen Psychiatry 1996; 53: 673–80
Pelc I, Verbands P, LeBon O, et al. Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients: a 90-day placebo-controlled dose finding study. Br J Psychiatry 1997; 171: 73–7
Paille FM, Guelfi JD, Perkins AC, et al. Double-blind randomized multicenter trial of acamprosate in maintaining abstinence from alcohol. Alcohol 1995; 30: 239–47
Litten RZ, Fertig J, Mattson M, et al. Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerg Drugs 2005; 10(2): 323–43
Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther 2006; 111(3): 855–76
Zeise ML, Kasparov S, Capogna M, et al. Acamprosate (calcium acetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. Eur J Pharmacol 1993; 231(1): 47–52
Littleton J, Zieglgansberger W. Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence. Am J Addict 2003; 12Suppl. 1: S3–11
Fuller RK, Gordis E. Does disulfiram have a role in alcoholism treatment today? Addiction 2004; 99(1): 21–4
Garbutt JC, West SL, Carey TS, et al. Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA 1999; 281(14): 1318–25
Fuller RK, Branchey L, Brightwell DR, et al. Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA 1986; 256(11): 1449–55
Gelkopf M, Bleich A, Hayward R, et al. Characteristics of benzodiazepine abuse in methadone maintenance treatment patients: a 1 year prospective study in an Israeli clinic. Drug Alcohol Depend 1999; 55(1–2): 63–8
Darke S, Hall W, Ross M, et al. Benzodiazepine use and HIV risk-taking behaviour among injecting drug users. Drug Alcohol Depend 1992; 31(1): 31–6
Gutierrez-Cebollada J, de la Torre R, Ortuno J, et al. Psychotropic drug consumption and other factors associated with heroin overdose. Drug Alcohol Depend 1994; 35(2): 169–74
Caplehorn JR. Deaths in the first two weeks of maintenance treatment in NSW in 1994: identifying cases of iatrogenic methadone toxicity. Drug Alcohol Rev 1998; 17(1): 9–17
The National Center on Addiction and Substance Abuse at Columbia University. Under the counter: the diversion and abuse of controlled prescription drugs in the US. New York: The National Center on Addiction and Substance Abuse at Columbia University, 2005
Wolf BC, Lavezzi WA, Sullivan LM, et al. One hundred seventy two deaths involving the use of oxycodone in Palm Beach County. J Forensic Sci 2005; 50(1): 192–5
de Wit H, Richards JB. Dual determinants of drug use in humans: reward and impulsivity. Nebr Symp Motiv 2004; 50: 19–55
Weizman T, Gelkopf M, Melamed Y, et al. Treatment of benzodiazepine dependence in methadone maintenance treatment patients: a comparison of two therapeutic modalities and the role of psychiatric comorbidity. Aust N Z J Psychiatry 2003; 37(4): 458–63
Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2004; 61(11): 1107–15
Rohsenow DJ, Monti PM, Colby SM, et al. Naltrexone treatment for alcoholics: effect on cigarette smoking rates. Nicotine Tob Res 2003; 5(2): 231–6
Gulliver SB, Rohsenow DJ, Colby SM, et al. Interrelationship of smoking and alcohol dependence, use and urges to use. J Stud Alcohol 1995; 56(2): 202–6
Wewers ME, Dhatt R, Tejwani GA. Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology 1998; 140(2): 185–90
Ahmadi J, Ashkani H, Ahmadi M, et al. Twenty-four week maintenance treatment of cigarette smoking with nicotine gum, clonidine and naltrexone. J Subst Abuse Treat 2003; 24(3): 251–5
Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis 1999; 18(1): 31–40
David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev 2001; (3): CD003086
Krishnan-Sarin S, Meandzija B, O’Malley S. Naltrexone and nicotine patch smoking cessation: a preliminary study. Nicotine Tob Res 2003; 5(6): 851–7
Wong GY, Wolter TD, Croghan GA, et al. A randomized trial of naltrexone for smoking cessation. Addiction 1999; 94(8): 1227–37
Byars JA, Frost-Pineda K, Jacobs WS, et al. Naltrexone augments the effects of nicotine replacement therapy in female smokers. J Addict Dis 2005; 24(2): 49–60
Mason B. Novel pharmacotherapy approaches: naltrexone crossed with nicotine patch (Nicotrol) for concurrent alcohol and tobacco dependence. In: Rohsenow DJ, Fertig J, editors. Smoking and alcohol abuse: from lab to clinic. Research Society on Alcoholism Satellite Meeting; 2005 Jun 25; Santa Barbara (CA)
Hurt RD, Patten CA, Offord KP, et al. Treating nondepressed smokers with alcohol dependence in sustained full remission: nicotine patch therapy tailored to baseline serum cotinine. J Stud Alcohol 2005; 66(4): 506–16
Cornelius JR, Salloum IM, Cornelius MD, et al. Preliminary report: double-blind, placebo-controlled study of fluoxetine in depressed alcoholics. Psychopharm Bull 1995; 31(2): 297–303
Cornelius JR, Salloum IM, Ehler JG, et al. Fluoxetine in depressed alcoholics: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 1997; 54(8): 700–5
Kranzler HR, Burleson JA, Korner P, et al. Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics.Am J Psychiatry 1995; 152(3): 391–7
Niaura R, Spring B, Borrelli B, et al. Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment. J Consult Clin Psychol 2002; 70(4): 887–96
Blondal T, Gudmundsson LJ, Tomasson K, et al. The effects of fluoxetine combined with nicotine inhalers in smoking cessation: a randomized trial. Addiction 1999; 94(7): 1007–15
Tanda G, Pontieri FE, Di Chiara G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mul opioid receptor mechanism. Science 1997; 276(5321): 2048–50
Freedland CS, Sharpe AL, Samson HH, et al. Effects of SR141716A on ethanol and sucrose self-administration. Alcohol Clin Exp Res 2000; 25(2): 277–82
De Vries TJ, Taco J, Shaham Y, et al. A cannabinoid mechanism in relapse to cocaine seeking. Nat Med 2001; 7(10): 1151–4
Navarro M, Carrera MR, Fratta W, et al. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci 2001; 21(14): 5344–50
Cohen C, Perrault G, Voltz C, et al. SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 2002; 13(5–6): 451–63
Peck P. Rimonabant helps for smoking scessation, weight loss [online]. Available from URL: http://www.medscape.com/viewarticle/471358 [Accessed 2007 Jul 2]
Soderpalm B, Ericson M, Olausson P, et al. Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol. Behav Brain Res 2000; 113(1–2): 85–96
White HS, Brown SD, Woodhead JH, et al. Topiramate modulates GABA-evoked currents in murine cortical neurons by nonbenzodiazepine mechanism. Epilepsia 2000; 41Suppl. 1: S25–9
Zhang X, Velumian AA, Jones OT, et al. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia 2000; 41Suppl. 1: S52–60
Johnson BA. Recent advances in the development of treatments for alcohol and cocaine dependence. CNS Drugs 2005; 19(10): 873–96
Cornish JL, Kalivas PW. Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 2000; 20(15): RC89
Johnson BA, Ait-Doud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 2003; 361: 1677–85
Johnson BA. Topiramate-induced neuromodulation of corticomesolimbic dopamine function: a new vista for the treatment of comorbid alcohol and nicotine dependence? Addict Behav 2004; 29(7): 1465–79
Carroll KM, Rounsavile BJ, Bryant KJ. Alcoholism in treatment-seeking cocaine abusers: clinical and prognostic significance. J Stud Alcohol 1993; 54: 199–203
Heil SH, Badger GJ, Higgins ST. Alcohol dependence among cocaine-dependent outpatients: demographics, drug use, treatment outcome and other characteristics. J Stud Alcohol 2001; 62: 14–22
Miller NS, Gold MS, Millman RB. Cocaine: general characteristics, abuse, and addiction. NY State J Med 1989; 89: 390–5
Schmitz JM, Bordnick PS, Kearney ML, et al. Treatment outcome of cocaine-alcohol dependent patients. Drug Alcohol Depend 1997; 47: 55–61
Brower KJ, Blow FC, Hill EM, et al. Treatment outcome of alcoholics with and without cocaine disorders. Alcohol Clin Exp Res 1994; 18: 734–9
Cornelius JR, Salloum IM, Thase ME, et al. Fluoxetine versus placebo in depressed alcoholic cocaine abusers. Psychopharmacol Bull 1998; 34(1): 117–21
Pettinati H. Innovative approaches for cocaine pharmacotherapy [online]. Available from URL: http://www.crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6941789&p_grant_num=5P50DA012756-07&p_query=&ticket=30798162&p_audit_session_id=200664827&p_keywords=+ [Accessed 2006 Aug 10]
Oslin DW, Pettinati HM, Volpicelli JR, et al. The effects of naltrexone on alcohol and cocaine use in dually addicted patients. J Subst Abuse Treat 1999; 16(2): 163–7
Schmitz JM, Stotts AL, Sayre SL, et al. Treatment of cocaine-alcohol dependence with naltrexone and relapse prevention therapy. Am J Addict 2004; 13(4): 333–41
Volpicelli JR. Alcohol abuse and alcoholism: an overview. J Clin Psychiatry 2001; 62Suppl. 20: 4–10
Kleber HD. Pharmacologic treatments for heroin and cocaine dependence. Am J Addict 2003; 12Suppl. 2: S5–18
Lima MS, Reisser AA, Soares BG, et al. Antidepressants for cocaine dependence. Cochrane Database Syst Rev 2003; (2): CD002950
Kosten TR, Morgan CM, Falcione J, et al. Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Arch Gen Psychiatry 1992; 49(11): 894–8
Carroll KM, Rounsaville BJ, Gordon LT, et al. Psychotherapy and pharmacotherapy for ambulatory cocaine abusers. Arch Gen Psychiatry 1994; 51(3): 177–87
Nunes EV, Levin FR. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA 2004; 291(15): 1887–96
Suh JJ, Pettinati HM, Kampman KM, et al. The status of disulfiram: a half of a century later. J Clin Psychopharm 2006; 26(3): 290–302
Sofuoglu M, Kosten TR. Novel approaches to the treatment of cocaine addiction. CNS Drugs 2005; 19(1): 13–25
Hameedi FA, Rosen MI, McCance-Katz EF, et al. Behavioral, physiological, and pharmacological interaction of cocaine and disulfiram in humans. Biol Psychiatry 1995; 37(8): 560–3
Higgins ST, Budney AJ, Bickel WK, et al. Disulfiram therapy in patients abusing cocaine and alcohol. Am J Psychiatry 1993; 150(4): 675–6
Carroll KM, Ziedonis D, O’Malley SS, et al. Pharmacologic interventions for abusers of alcohol and cocaine: a pilot study of disulfiram versus naltrexone. Am J Addictions 1993; 2: 77–9
Carroll KM, Nich C, Ball SA, et al. Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction 1998; 93(5): 713–27
Carroll KM, Fenton LR, Ball SA, et al. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial. Arch Gen Psychiatry 2004; 61(3): 264–72
Misgeld U, Bijak M, Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol 1995; 46(4): 423–62
Cousins MS, Roberts DC, de Wit H. GABA(B) receptor agonists for the treatment of drug addiction: a review of recent findings. Drug Alcohol Depend 2002; 65(3): 209–20
Anstrom KK, Cromwell HC, Markowski T, et al. Effect of baclofen on alcohol and sucrose self-administration in rats. Alcohol Clin Exp Res 2003; 27(6): 900–8
Colombo G, Vacca G, Serra S, et al. Baclofen suppresses motivation to consume alcohol in rats. Psychopharmacology 2003; 167(3): 221–4
Vocci F, Ling W. Medications development: successes and challenges. Pharmacol Ther 2005; 108(1): 94–108
Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol 2002; 37(5): 504–8
Shoptaw S, Yang X, Rotheram-Fuller EJ, et al. Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 2003; 64(12): 1440–8
Kenna GA. Rationale for use of aripiprazole for alcohol dependence treatment. Drugs Future 2003; 28(12): 1227–34
Hutchison KE, Ray L, Sandman E, et al. The effect of olanzapine on craving and alcohol consumption. Neuropsychopharmacology 2006; 31(6): 1310–7
Hutchison KE, Wooden A, Swift RM, et al. Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction. Neuropsychopharmacology 2003; 28(10): 1882–8
Reid MS, Casadonte P, Baker S, et al. A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L-carnitine for the treatment of cocaine dependence. Addiction 2005; 100Suppl. 1: 43–57
Smelson DA, Ziedonis D, Williams J, et al. The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report. J Clin Psychopharm 2006; 26(1): 9–12
Kampman KM, Pettinati H, Lynch KG, et al. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend 2004; 75(3): 233–40
Taylor CP, Gee NS, Su TZ, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998; 29(3): 233–49
Myrick H, Henderson S, Brady KT, et al. Gabapentin in the treatment of cocaine dependence: a case series. J Clin Psychiatry 2001; 62(1): 19–23
Myrick H, Malcolm R, Brady KT. Gabapentin treatment of alcohol withdrawal. Am J Psychiatry 1998; 155(11): 1632
Voris J, Smith NL, Rao SM, et al. Gabapentin for the treatment of ethanol withdrawal. Substance Abuse 2003; 24(2): 129–32
Mason B. Gabapentin treatment of alcohol dependence [online]. Available from URL: http://www.crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=70270198&p_grant_num=5R37AA014028-05&p_query=(gabapentin+%26+alcohol)&ticket=30797190&p_audit_session_id=200663003&p_audit_score =100&p_audit_numfound=l&p_keywords=gabapentin+alcohol [Accessed 2006 Aug 10]
Kushner SA, Dewey SL, Kornetsky C. The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats. J Pharmacol Exp Ther 1999; 290: 797–802
Bisaga A, Aharonovich E, Garawi F, et al. A randomized placebo-controlled trial of gabapentin for cocaine dependence. Drug Alcohol Depend 2006; 81(3): 267–74
Hart CL, Ward AS, Collins ED, et al. Gabapentin maintenance decreases smoked cocaine-related subjective effects, but not self-administration by humans. Drug Alcohol Depend 2004; 73(3): 279–87
Hart CL, Haney M, Collins ED, et al. Smoked cocaine self-administration by humans is not reduced by large gabapentin maintenance doses. Drug Alcohol Depend 2007; 86(2–3): 274–7
Haney M, Hart C, Collins ED, et al. Smoked cocaine discrimination in humans: effects of gabapentin. Drug Alcohol Depend 2005; 80(1): 53–61
Berger SP, Winhusen TM, Somoza EC, et al. A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence. Addiction 2005; 100Suppl. 1: 58–67
Loscher W. Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs 2002; 16(10): 669–94
Longo LP, Campbell T, Hubatch S. Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. J Addict Dis 2002; 21(2): 55–64
Halikas JA, Center BA, Pearson VL, et al. A pilot, open clinical study of Depakote in the treatment of cocaine abuse. Hum Psychopharmacol 2001; 16(3): 257–64
Myrick H, Henderson S, Brady KT, et al. Divalproex loading in the treatment of cocaine dependence. J Psychoactive Drugs 2001; 33(3): 283–7
Brady KT, Myrick H, Henderson S, et al. The use of divalproex in alcohol relapse prevention: a pilot study. Drug Alcohol Depend 2002; 67(3): 323–30
Myrick H, Brady KT. The use of divalproex in the treatment of addictive disorders. Psychopharmacol Bull 2003; 37Suppl. 2: 89–97
Johnson BA, Ait-Dowd N. Neuropharmacological treatments for alcoholism: scientific basis and clinical findings. Psychopharmacology 2000; 149: 327–44
Sellers EM, Toneatto T, Romach MK, et al. Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence. Alcohol Clin Exp Res 1994; 18(4): 879–85
Johnson BA, Roache J, Javors MA, et al. Ondansetron for reduction of drinking among biologically predisposed patients: a randomized controlled trial. JAMA 2000; 284: 963–71
Johnson BA, Roache JD, Ait-Daoud N, et al. A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence. Drug Alcohol Depend 2006; 84(3): 256–63
Peles E, Kreek MJ, Kellogg S, et al. High methadone dose significantly reduces cocaine use in methadone maintenance treatment (MMT) patients. J Addict Dis 2006; 25(1): 43–50
Leri F, Bruneau J, Stewart J. Understanding polydrug use: review of heroin and cocaine co-use. Addiction 2003; 98(1): 7–22
Preston KL, Sullivan JT, Strain EC, et al. Enhancement of cocaine’s abuse liability in methadone maintenance patients. Psychopharmacology 1996; 123(1): 15–25
Kosten TR, Rosen MI, Schottenfeld R, et al. Buprenorphine for cocaine and opiate dependence. Psychopharmacol Bull 1992; 28(1): 15–9
Montoya ID, Gorelick DA, Preston KL, et al. Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence. Clin Pharmacol Ther 2004; 75(1): 34–48
Schottenfeld RS, Chawarski MC, Pakes JR, et al. Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. Am J Psychiatry 2005; 162(2): 340–9
Kosten TR, Schumann B, Wright D, et al. A preliminary study of desipramine in the treatment of cocaine abuse in methadone maintenance patients. J Clin Psychiatry 1987; 48(11): 442–4
Arndt IO, Dorozynsky L, Woody GE, et al. Desipramine treatment of cocaine dependence in methadone-maintained patients. Arch Gen Psychiatry 1992; 49(11): 888–93
Batki SL, Manfredi LB, Jacob P, et al. Fluoxetine for cocaine dependence in methadone maintenance: quantitative plasma and urine cocaine/benzoylecgonine concentrations. J Clin Psychopharm 1993; 13(4): 243–50
Pollack MH, Rosenbaum JF. Fluoxetine treatment of cocaine abuse in heroin addicts. J Clin Psychiatry 1991; 52(1): 31–3
Grabowski J, Rhoades H, Elk R, et al. Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials. J Clin Psychopharm 1995; 15(3): 163–74
Poling J, Oliveto A, Petry N, et al. Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population. Arch Gen Psychiatry 2006; 63(2): 219–28
Petrakis IL, Carroll KM, Nich C, et al. Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Addiction 2000; 95(2): 219–28
George TP, Chawarski MC, Pakes J, et al. Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial. Biol Psychiatry 2000; 47(12): 1080–6
Andersen KE, Braestrup C, Gronwald FC, et al. The synthesis of novel GABA uptake inhibitors: 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-(4,4-Bis(3-methyl-2-thienyl)-3-butenyl)-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate. J Med Chem 1993; 36: 1716–25
Sofuoglu M, Poling J, Mitchell E, et al. Tiagabine affects the subjective responses to cocaine in humans. Pharmacol Biochem Behav 2005; 82(3): 569–73
Gonzalez G, Sevaroni K, Sofuoglu M, et al. Tiagabine increases cocaine-free urines in cocaine-dependent methadone-treated patients: results from a randomized pilot study. Addiction 2003; 98: 1625–32
Winhusen TM, Somoza EC, Harrer JM, et al. A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments. Addiction 2005; 100Suppl. 1: 68–77
Gerardo Gonzalez G, Desai R, Sofuoglu M, et al. Clinical efficacy of gabapentin versus tiagabine for reducing cocaine use among cocaine-dependent methadone-treated patients. Drug Alcohol Depend 2007; 87(1): 1–9
Haney M, Hart CL, Foltin RW. Effects of baclofen on cocaine self-administration: opioid- and nonopioid-dependent volunteers. Neuropsychopharmacology 2006; 31(8): 1814–21
Shoptaw S, Yang X, Rotheram-Fuller EJ, et al. Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 2003; 64(12): 1440–8
Acknowledgements
No sources of funding were used to assist in the preparation of this review.
Dr Robert Swift has acted as a consultant to Pfizer, Ortho-McNeill, Forest and Alkermes, has received honoraria from Pfizer and Forest, and has received grants from Pfizer, Ortho-McNeill and Forest. The other authors have no conflicts of interest that are directly relevant to the content of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kenna, G.A., Nielsen, D.M., Mello, P. et al. Pharmacotherapy of Dual Substance Abuse and Dependence. CNS Drugs 21, 213–237 (2007). https://doi.org/10.2165/00023210-200721030-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-200721030-00003