New treatments for cocaine dependence: a focused review

Abstract

Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.

Design, Preparation, and Characterization of High-Activity Mutants of Human Butyrylcholinesterase Specific for Detoxification of Cocaine

“…There is no U.S. Food and Drug Administration-approved medication specific for cocaine abuse treatment. The disastrous medical and social consequences of cocaine abuse have made a high priority the development of an anticocaine medication (Karila et al, 2008;Xi and Gardner, 2008). It would be an ideal anticocaine medication to accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma] (Landry et al, 1993;Kamendulis et al, 1996;Carrera et al, 2004;Meijler et al, 2005;Gorelick, 2008).…”

A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine

“…Despite decades of research, no effective treatment is available for cocaine addiction (Karila et al, 2008;Ross and Peselow, 2009;Schmidt and Pierce, 2010). It would be invaluable to have a better understanding of the molecular, cellular, and system-wide changes that accompany addiction.…”

Effects of Varenicline on the Reinforcing and Discriminative Stimulus Effects of Cocaine in Rhesus Monkeys

“…More recently, researchers have examined neurotransmitter systems that indirectly modulate DA activity (e.g., Karila et al, 2008). For example, interactions between the acetylcholine (ACh) and DA neurotransmitter systems have implications for drug development to treat addiction (Lester et al, 2010).…”