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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    • "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.
    Psychopharmacology 08/2013; 229(3). DOI:10.1007/s00213-013-3232-4 · 3.88 Impact Factor
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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
    PLoS ONE 07/2013; 8(7):e69224. DOI:10.1371/journal.pone.0069224 · 3.23 Impact Factor
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    • "Evidently, other neurotransmitters such as norepinephrine and acetylcholine also regulate activation in this network and consequently are associated with inhibitory control capacity (Nieuwenhuis and Jepma, 2011; Sarter et al., 2009). Recent work has examined whether improving norepinephrine and dopamine levels by medication such as modafinil may concurrently increase inhibitory control (Brady et al., 2011). Indeed, it has recently been shown that modafinil improved inhibitory control in methamphetamine and alcohol dependent individuals (Dean et al., 2011; Schmaal et al., 2012). "
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    ABSTRACT: Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of inhibitory control is still insufficiently clear. The aims of the current study were twofold. First, we investigated the role of dopamine in inhibitory control and associated brain activation. Second, the proposed link between dopamine and impaired inhibitory control in nicotine dependence was investigated by comparing smokers and non-smoking controls. Haloperidol (2mg), a dopamine D2/D3 receptor antagonist, and placebo were administered to 25 smokers and 25 non-smoking controls in a double-blind randomized cross-over design while performing a Go/NoGo task during fMRI scanning. Haloperidol reduced NoGo accuracy and associated brain activation in the ACC, right SFG and left IFG, showing that optimal dopamine levels are crucial to effectively implement inhibitory control. In addition, smokers showed behavioral deficits on the Go/NoGo task as well as hypoactivity in the left IFG, right MFG and ACC after placebo, supporting the hypothesis of a hypoactive prefrontal system in smokers. Haloperidol had a stronger impact on prefrontal brain activation in non-smoking controls compared to smokers, which is in line with the inverted 'U' curve theory of dopamine and cognitive control. The current findings suggest that altered baseline dopamine levels in addicted individuals may contribute to the often observed reduction in inhibitory control in these populations.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 11/2012; 23(10). DOI:10.1016/j.euroneuro.2012.10.017 · 4.37 Impact Factor
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