Cognitive enhancers in the treatment of substance use disorders: Clinical evidence

Medical University of South Carolina, Department of Psychiatry, 67 President Street, Charleston, SC 29425, USA.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 08/2011; 99(2):285-94. DOI: 10.1016/j.pbb.2011.04.017
Source: PubMed


Attenuation of drug reward has been the major focus of medication development in the addiction area to date. With the growth of research in the area of cognitive neuroscience, the importance of executive function and inhibitory cognitive control in addictive disorders is becoming increasingly apparent. An emerging strategy in the pharmacotherapy of addictions and other psychiatric disorders involves the use of medications that improve cognitive function. In particular, agents that facilitate inhibitory and attentional control, improve abstraction, planning and mental flexibility could be beneficial in the treatment of substance use disorders. Because there are multiple neurotransmitter systems involved in the regulation of cognitive function, agents from a number of drug classes have been tested. In particular, agents acting through the cholinergic, adrenergic and glutamatergic systems have shown potential for improving cognitive function in a number of psychiatric and neurologic disorders, but most of these agents have not been tested in the treatment of individuals with substance use disorders. This manuscript provides a review of clinical data supporting the use of the major classes of cognitive enhancing agents in substance use disorders. Agents that have shown promise in cognitive enhancement in other disorders, and have a theoretical or mechanistic rationale for application to substance use disorders are also highlighted.

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Available from: Kathleen Brady
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    • "Thus, the effects of MOD on improving attention and cognitive function in healthy subjects have provided insight into its neuropsychological actions, free from confounds of any underlying pathology (Morein-Zamir et al. 2007). Moreover, treatment (or adjunctive treatment) of neuropsychological disorders such as drug abuse and addiction with cognitive enhancers such as MOD or R-MOD may be more effective than current strategies (Brady et al. 2011). This idea is particularly appealing for the treatment of cocaine and/or methamphetamine (MA) abuse, as there are no effective medications currently available (Dean et al. 2011; Ghahremani et al. 2011). "
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    ABSTRACT: Modafinil (MOD) and its R-enantiomer (R-MOD) are approved medications for narcolepsy and other sleep disorders. They have also been used, off-label, as cognitive enhancers in populations of patients with mental disorders, including substance abusers that demonstrate impaired cognitive function. A debated nonmedical use of MOD in healthy individuals to improve intellectual performance is raising questions about its potential abuse liability in this population. MOD has low micromolar affinity for the dopamine transporter (DAT). Inhibition of dopamine (DA) reuptake via the DAT explains the enhancement of DA levels in several brain areas, an effect shared with psychostimulants like cocaine, methylphenidate, and the amphetamines. However, its neurochemical effects and anatomical pattern of brain area activation differ from typical psychostimulants and are consistent with its beneficial effects on cognitive performance processes such as attention, learning, and memory. At variance with typical psychostimulants, MOD shows very low, if any, abuse liability, in spite of its use as a cognitive enhancer by otherwise healthy individuals. Finally, recent clinical studies have focused on the potential use of MOD as a medication for treatment of drug abuse, but have not shown consistent outcomes. However, positive trends in several result measures suggest that medications that improve cognitive function, like MOD or R-MOD, may be beneficial for the treatment of substance use disorders in certain patient populations.
    Full-text · Article · Aug 2013 · Psychopharmacology
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    • "Strong pre-clinical and clinical data support the use of modafinil. Modafinil administration has been shown to improve cognitive functions in mice [47], rats [48], sleep-deprived healthy adults [49], substance abusers [46], [50], and healthy adults [51], [14]. Cognitive improvement has been observed in several domains, including attentional control, working memory, and fluid reasoning, all processes that are critical components of Gf performance. "
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    ABSTRACT: There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven's Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. NCT01684306
    Full-text · Article · Jul 2013 · PLoS ONE
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    • "Since the establishment of the involvement of N-methyl-daspartate (NMDA) receptors during extinction learning in fear conditioning studies and reports of d-cycloserine facilitating conditioned fear extinction learning [5], interest in the use of NMDA receptor co-agonists during extinction training for the treatment of addiction has increased substantially. Recent attention has been given to d-cycloserine, a partial agonist at the co-agonist site on the NMDA receptor, for the treatment of cocaine addiction [6]. Various studies have revealed the efficacy of d-cycloserine to facilitate extinction and reduce drug-seeking using both the conditioned place preference (CPP) and the self-administration behavioral paradigms [7]. "
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    ABSTRACT: With respect to the treatment of addiction, the objective of extinction training is to decrease drug-seeking behavior by repeatedly exposing the patient to cues in the absence of unconditioned reinforcement. Such exposure therapy typically takes place in a novel (clinical) environment. This is potentially problematic, as the effects of extinction training include a context dependent component and therefore diminished efficacy is expected upon the patient's return to former drug-seeking/taking environments. We have reported that treatment with the NMDAR coagonist d-serine is effective in facilitating the effects of extinction to reducing cocaine-primed reinstatement. The present study assesses d-serine's effectiveness in reducing drug-primed reinstatement under conditions in which the context of extinction training is altered in rats self-administering cocaine. After 22 days of cocaine self-administration (0.5mg/kg) in context "A", animals underwent 5 extinction training sessions in context "B". Immediately after each extinction session in "B", animals received either saline or d-serine (60mg/kg) treatment. Our results indicate that d-serine treatment following extinction in "B" had no effect on either IV or IP cocaine-primed reinstatement conducted in "A". These results stand in contrast to our previous findings where extinction occurred in "A", indicating that d-serine's effectiveness in facilitating extinction training to reduce drug-primed reinstatement is not transferable to a novel extinction environment. This inability of d-serine treatment to reduce the context specificity of extinction training may explain the inconsistent effects observed in clinical studies published to date in which adjunctive cognitive enhancement treatment has been combined with behavioral therapy without significant benefit.
    Full-text · Article · Jun 2013 · Behavioural brain research
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