Cocaine abuse

There is some evidence of a synergistic effect on reinforcement with concurrent administration of benzodiazepines and opioids (Walker and Ettenberg 2003). Cocaine abusers are less likely than opioid abusers to abuse benzodiazepines, preferring alcohol and opioids as secondary drugs of abuse. The most common pattern of benzodiazepine misuse in these individuals is intermittent use of therapeutic or supratherapeutic doses to counter unwanted effects of cocaine. 

The development of effective pharmacotherapy has lagged behind progress in understanding the reward mechanisms and chronic impairments underlying stimulant abuse. Pharmacological and behavioral treatment approaches that have been used for cocaine abuse have not been as widely tested for the treatment of amphetamine abuse, limiting what can be offered for treatment of this disorder. No treatment agents are approved by the FDA for treatment of cocaine or amphetamine dependence. 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

A meta-analysis of placebo-controlled studies by Levin and Lehman (1991) showed that desipramine produced greater cocaine abstinence than placebo. Although a more recent review did not concur (Lima et al. 2001), secondary analyses of studies with imipramine, desipramine, and bupropion suggested that depressed cocaine abusers are more likely to show significant reductions in cocaine abuse than nondepressed cocaine abusers (Margolin et al. 1995 Nunes et al. 1991 Ziedonis and Kosten 1991). Furthermore, recent work with desipramine supported its efficacy in opioid-dependent patients, particularly in combination with contingency management therapies (Kosten et al. 2004 Oliveto et al. 1999). 

Beatty WW, Katzung VM, Moreland VJ, et al Neuropsychological performance of recently abstinent alcoholics and cocaine abusers. Drug Alcohol Depend 37 247— 233, 1995... 

Ben-Shahar O, Ahmed SH, Koob GF, et al The transition from controlled to compulsive drug use is associated with a loss of sensitization. Brain Res 995 46—54, 2004 Bolla KI, Cadet JL, London ED The neuropsychiatry of chronic cocaine abuse. J Neuropsychiatry Clin Neurosci 10 280-289, 1998... 

Kosten TR, Kleber HD Rapid death during cocaine abuse a variant of the neuroleptic malignant syndrome Am J Drug Alcohol Abuse 14 335-346, 1988 Kosten TR, Kleber HD, Morgan C Treatment of cocaine abuse with buprenorphine. Biol Psychiatry 26 637—639, 1989... 

Oliveto AH, Feingold A, Schottenfeld R, et al Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Arch Gen Psychiatry 56 812-820, 1999... 

Schmitz JM, Averill P, Stotts AL, et al Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug Alcohol Depend 63 207-214,2001 Schottenfeld RS, Pakes JR, Oliveto A, et al Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry 54 713-720, 1997... 

Weiss RD, Mirin SM, Michael JL, et al Psychopathology in chronic cocaine abusers. 

In other substance use disorders, the use of 12-step interventions is also popular, and participation in 12-step groups is correlated with better outcomes in cocaine abusers (e.g., McKay et al. 1994). However, a smdy of 128 cocaine abusers found that cognitive-behavioral therapy was more efficacious than 12-step facilitation in engendering cocaine abstinence (Maude-Griffm et al. 1998). Thus, the relative efficacy of 12-step approaches for drug use disorders requires further investigation. No known studies have systematically evaluated the efficacy of 12-step treatments in opioid-dependent patients, either alone or in conjunction with pharmacotherapies. 

Rawson RA, Huber A, McCann M, et al A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence. Arch Gen Psychiatry 59 817—824, 2002 Rohsenow DJ, Monti PM, Martin RA, et al Motivational enhancement and coping skills training for cocaine abusers effect on substance use outcomes. Addiction... 

Zhan C-G (2006) Modeling Reaction Mechanism of Cocaine Hydrolysis and Rational Drug Design for Therapeutic Treatment of Cocaine Abuse. 4 107-159 Zuccato C, see Gambari R (2007) 9 265-276... 

Scheme 4.14 S Tithesis of cocaine-abuse therapeutic agent.

Cregler, L.L., and Mark, H. Medical complications of cocaine abuse. 

Gawin, F.H., and Kleber, H.D. Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Arch Gen Psychiatry 43 107-113, 1986. 

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