Cognitive enhancement as a pharmacotherapy target for stimulant addiction.
BACKGROUND
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.


OBJECTIVE
To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward.


METHODS
Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed.


CONCLUSIONS
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.
Sofuoglu
Mehmet
M
Yale University, School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, West Haven, CT 06516, USA. mehmet.sofuoglu@yale.edu
D000109:Acetylcholine / Q000502:physiology; D018663:Adrenergic Agents / Q000627:therapeutic use; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001288:Attention / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D003657:Decision Making / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy; D008570:Memory, Short-Term / Q000187:drug effects; D018722:Nicotinic Agonists / Q000627:therapeutic use; D018697:Nootropic Agents / Q000627:therapeutic use; D009638:Norepinephrine / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome
D018663:Adrenergic Agents; D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D000109:Acetylcholine; D009638:Norepinephrine