Article

An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: A pilot study

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, United States
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 4.03). 04/2007; 31(2):389-94. DOI: 10.1016/j.pnpbp.2006.10.001
Source: PubMed

ABSTRACT Recent preclinical studies implicate N-acetylcysteine (NAC), a cysteine prodrug, as a potential medication for preventing relapse to cocaine use; however, little is known about the safety and tolerability of NAC in cocaine-dependent subjects in an outpatient setting. This pilot study examines the safety and tolerability of 3 doses of NAC for the treatment of cocaine dependence. Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received NAC at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested that the three doses were well tolerated. Overall, the retention rates appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The majority of subjects who completed the study (n=16) either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment. Overall the findings suggest that it is feasible to treat cocaine-dependent treatment seekers with N-acetylcysteine on an outpatient basis.

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    • "Recognition of the importance of redox and epigenetic mechanisms in addiction brings the prospect of novel targets. Use of N-acetylcysteine in symptomatic treatment of alcohol (Ferreira Seiva et al., 2009), cocaine dependence (Mardikian et al., 2007), and withdrawal (Reichel et al., 2011) presents efforts in exploiting this pathway. EAAT3 itself may provide a potential site for pharmacologic intervention, along with factors/systems which regulate its activity. "
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    • "Results presented here support a critical role for druginduced downregulation of accumbens GLT-1 in the vulnerability to relapse, and that the restoration of GLT-1 by daily NAC treatments is a critical mechanism whereby NAC inhibits reinstated cocaine seeking. Importantly, while a number of studies demonstrate pre-clinical and clinical efficacy of NAC against cocaine seeking, results are not unilaterally positive (Mardikian et al. 2007; Berk et al. 2013). For example, in a recent double-blind placebo-controlled study of NAC for cocaine dependence over 8 weeks for outpatient, treatment-seeking users, overall use was not statistically different between groups (LaRowe et al. 2013). "
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    • "Some of these are being tested clinically, as in the case of N-acetylcysteine, which targets the cystine-glutamate exchanger and helps restore glutamate homeostasis and neuronal plasticity (Moussawi et al., 2011). Early clinical trials with N-acetylcysteine for the treatment of cocaine and nicotine addictions have shown positive results (Knackstedt et al., 2009; Mardikian et al., 2007). Other targets of interest include mGluR2/3 agonists, mGluR5 negative allosteric modulators, stimulators of glutamate transport, and inhibitors of either AMPA or NMDA receptors. "
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