SAR-39684-the-neurocircuitry-of-illicit-psychostimulant-addiction--an-_020713.pdf

175 clinical trials have thus far been mixed with one

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175 Clinical trials have thus far been mixed, with one study finding reduced cocaine craving and use, and another study showing increased cocaine use. 176,177 Recent evidence for dysregulation of glutamatergic signaling in addiction has led to the testing of N -acetylcysteine, a derivative of the amino acid cysteine that normalizes extracellular levels of Glu following cocaine administration. 178,179 Clinical trials found that N- acetylcysteine treatment attenuates cocaine craving and use and normalizes brain glutamate levels. 180–182 Other recent studies found trends toward significant reductions in METH use and craving produced by the antidepressant buproprion and the anticonvulsant topiramate, which has glutamate release-inhibiting properties. 183,184 While these compounds have not demonstrated overwhelming efficacy in reducing psychostimulant use or craving in all subjects tested, trends toward effects were observed and thus merit further investigation. Other compounds that have been tested, with disappointing results, include β -adrenergic antagonists, submit your manuscript | Dove press Dove press 37 Neurocircuitry of illicit psychostimulant addiction Substance Abuse and Rehabilitation downloaded from by 71.51.178.127 on 08-Aug-2018 For personal use only. 1 / 1
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Substance Abuse and Rehabilitation 2013:4 opioid-receptor antagonists, 5-HT 3 -receptor antagonists, antidepressants, and anticonvulsants. 172,185–190 Despite the lack of past successes, several newer medications are currently being investigated and have shown some initial success, such as the smoking-cessation aid varenicline, the α 2 adrenergic agonist clonidine, and the antidepressant mirtazapine. 191–194 In addition, preclinical evidence strongly suggests potential therapeutic effects of compounds targeting receptors for endocannabinoids, the neuropeptide orexin, and CRF for the prevention of relapse to psychostimulant use. 195–197 Future approaches for the treatment of psychostimulant- induced cognitive deficits and dependence include the use of cognitive enhancers. 198–200 Two promising examples include prescription stimulants, such as modafinil and methylphenidate, which have shown modest but potential treatment effects in METH users and cocaine users with comorbid attention deficit/hyperactivity disorder, respectively. 201–205 In addition, galantamine, a cholinergic modulator and cognitive enhancer, has been reported to both decrease cocaine use and improve sustained attention in dependent subjects. 206,207 Together, these studies indicate that clinical trials of cognitive enhancers in the treatment of psychostimulant addiction are warranted. In addition to the pharmacological trials reviewed above, less conventional strategies that are gaining scientific momentum include vaccine therapies to immunoneutralize drug molecules and impede penetrance across the blood– brain barrier, enzyme conjugates that dramatically increase the metabolic breakdown of abused drugs, pharmacogenetic approaches based on individual genetic polymorphisms in addiction-related genes, and epigenetic modulators of drug- induced changes in gene expression.
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