title: Novel approaches to the treatment of cocaine addiction.
abstract: Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Although there are no approved pharmacotherapies for cocaine addiction, a number of medications have been tested with some promising results. In this review, we summarise some of the emerging targets for cocaine pharmacotherapy including dopaminergic and GABA medications, adrenoceptor antagonists, vasodilators and immunotherapies. The brain dopamine system plays a significant role in mediating the rewarding effects of cocaine. Among dopaminergic agents tested for cocaine pharmacotherapy, disulfiram has decreased cocaine use in a number of studies. Amantadine, another medication with dopaminergic effects, may also be effective in cocaine users with high withdrawal severity. GABA is the main inhibitory neurotransmitter in the brain, and accumulating evidence suggests that the GABA system modulates the dopaminergic system and cocaine effects. Two anticonvulsant medications with GABAergic effects, tiagabine and topiramate, have yielded positive findings in clinical trials. Baclofen, a GABA(B) receptor agonist, is also promising, especially in those with more severe cocaine use. Some of the physiological and behavioural effects of cocaine are mediated by activation of the adrenergic system. In cocaine users, propranolol, a beta-adrenoceptor antagonist, had promising effects in individuals with more severe cocaine withdrawal symptoms. Cerebral vasodilators are another potential target for cocaine pharmacotherapy. Cocaine users have reduced cerebral blood flow and cortical perfusion deficits. Treatment with the vasodilators amiloride or isradipine has reduced perfusion abnormalities found in cocaine users. The functional significance of these improvements needs to be further investigated. All these proposed pharmacotherapies for cocaine addiction act on neural pathways. In contrast, immunotherapies for cocaine addiction are based on the blockade of cocaine effects peripherally, and as a result, prevent or at least slow the entry of cocaine into the brain. A cocaine vaccine is another promising treatment for cocaine addiction. The efficacy of this vaccine for relapse prevention is under investigation. Many initial promising findings need to be replicated in larger, controlled clinical trials.
authors.affiliation: School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, Yale University, 950 Campbell Ave., Bldg 36/116A4, West Haven, CT 06516, USA. mehmet.sofuglu@yale.edu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sofuoglu
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
mesh_terms: D018663:Adrenergic Agents / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000453:epidemiology / Q000628:therapy*; D004221:Disulfiram / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000627:therapeutic use*; D004837:Epinephrine / Q000378:metabolism; D018682:GABA Agents / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D015259:Dopamine Agents; D018682:GABA Agents; D014665:Vasodilator Agents; D005680:gamma-Aminobutyric Acid; D004221:Disulfiram; D004298:Dopamine; D004837:Epinephrine