N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research

Abstract

Substance use disorder (SUD) is a chronic brain condition, with compulsive and uncontrollable drug-seeking that leads to long-lasting and harmful consequences. The factors contributing to the development of SUD, as well as its treatment settings, are not fully understood. Alterations in brain glutamate homeostasis in humans and animals implicate a key role of this neurotransmitter in SUD, while the modulation of glutamate transporters has been pointed as a new strategy to diminish the excitatory glutamatergic transmission observed after drugs of abuse. N-acetylcysteine (NAC), known as a safe mucolytic agent, is involved in the regulation of this system and may be taken into account as a novel pharmacotherapy for SUD. In this paper, we summarize the current knowledge on the ability of NAC to reduce drug-seeking behavior induced by psychostimulants, opioids, cannabinoids, nicotine, and alcohol in animals and humans. Preclinical studies showed a beneficial effect in animal models of SUD, while the clinical efficacy of NAC has not been fully established. In summary, NAC will be a small add-on to usual treatment and/or psychotherapy for SUD, however, further studies are required.

Prefrontal Cortical Control of Activity in Nucleus Accumbens Core Is Weakened by High-Fat Diet and Prevented by Co-Treatment with N-Acetylcysteine: Implications for the Development of Obesity

“…The present study gave rise to positive results in favor of N-Acetylcysteine treatment of high-fat diet addiction-like symptoms, a syndrome that can be observed in people as it is being investigated in the medical area [ 58 ]. N-Acetylcysteine has been used in some limited trials with promising results in treating people with cocaine-dependence [ 59 ], but the clinical efficacy of NAC in substance use disorders has not been fully established [ 60 ].…”

Glutamate as a Target Therapy for Alcohol Dependence Disorder

“…Moreover, this antiporter supplies tone to mGluRs and amino acid cysteine for synthesis of glutathione, so prevent formation of free radicals and oxidative stress (27,36). Restitution activity of this antiporter occur by either systemic administration of N-acetyl cysteine or by intracranial perfusion of cysteine has been demonstrate to diminish of cocaine and alcohol seeking in rat patterns (37). Further studies showed that ceftriaxone therapy rejuvenate both levels of GLT1 and xCT, which in sequence prevent reversion to cocaine and alcohol-seeking behavior (38,39).…”

Reactive Sulfur Compounds in the Fight against COVID-19

“…Although the therapeutic properties of NAC have been known for over half a century, subsequent scientific reports indicate an increasingly wider spectrum of its pharmacological activity. More recent studies have investigated the potential use of NAC in psychiatric and neurological disorders including Alzheimer’s and Parkinson’s diseases, schizophrenia, depression, bipolar disorder [ 66 , 67 , 68 , 69 ], and drug use disorder [ 70 ]. Moreover, the available data suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders [ 71 , 72 ].…”