Yale University, School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Addiction. 2010 Jan;105(1):38-48. doi: 10.1111/j.1360-0443.2009.02791.x.
No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system.
To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward.
Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed.
Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha(2)-adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction.
目前尚无药物被证实对可卡因和甲基苯丙胺成瘾有效。减弱药物奖赏一直是药物开发的主要策略，但这种方法并未导致有效的治疗方法。因此，除了大脑奖赏系统外，还需要确定新的治疗靶点。
提出一种针对兴奋剂成瘾的新型治疗策略，该策略将侧重于增强认知功能和减弱药物奖赏的药物治疗。
回顾了关于认知增强剂在兴奋剂成瘾药物治疗中潜在应用的临床前和临床文献。
可卡因和甲基苯丙胺使用者表现出明显的认知障碍，特别是在注意力、工作记忆和反应抑制功能方面。认知障碍似乎与较差的治疗保留和结果相关。针对乙酰胆碱和去甲肾上腺素的药物特别适合增强兴奋剂使用者的认知功能。许多胆碱能和去甲肾上腺素能药物已经上市，具有良好的安全性和低滥用潜力。这些药物包括加兰他敏、多奈哌齐和利斯的明（胆碱酯酶抑制剂）、伐伦克林（部分尼古丁激动剂）、胍法辛（α2-肾上腺素能激动剂）和托莫西汀（去甲肾上腺素转运蛋白抑制剂）。需要设计未来的临床研究，最佳地测量认知功能以及药物使用行为，以测试这些认知增强剂对兴奋剂成瘾的疗效。
