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Potential role of N-acetylcysteine in the management of substance use disorders.

ABSTRACT: There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will focus specifically on N-acetylcysteine (NAC), a safe and well-tolerated glutamatergic agent, as a promising potential pharmacotherapy for the treatment of SUDs across several substances of abuse. Building on recently published reviews of the clinical efficacy of NAC across a broad range of conditions, this review will more specifically discuss NAC as a pharmacotherapy for SUDs, devoting particular attention to the safety and tolerability profile of NAC, the wealth of preclinical evidence that has demonstrated the role of glutamate dysregulation in addiction, and the limited but growing clinical literature that has assessed the efficacy of NAC across multiple substances of abuse. Preliminary clinical studies show the promise of NAC in terms of safety, tolerability, and potential efficacy for promoting abstinence from cocaine, nicotine, and cannabis. Results from randomized clinical trials have been mixed, but several mechanistic and methodological factors are discussed to refine the use of NAC in promoting abstinence and relapse prevention across several substances of abuse. Further preclinical and clinical investigation into the use of NAC for SUDs will be vital in addressing current deficits in the treatment of SUDs.

SUBMITTER: McClure EA

PROVIDER: S-EPMC4009342 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Potential role of N-acetylcysteine in the management of substance use disorders.

McClure Erin A EA Gipson Cassandra D CD Malcolm Robert J RJ Kalivas Peter W PW Gray Kevin M KM

CNS drugs 20140201 2

There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will ...[more]

PMID: 24442756

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Project description:Drug treatments available for the management of substance use disorders (SUD) present multiple limitations in efficacy, lack of approved treatments or alarming relapse rates. These facts hamper the clinical outcome and the quality of life of the patients supporting the importance to develop new pharmacological agents. Lately, several reports suggest that cannabidiol (CBD) presents beneficial effects relevant for the management of neurological disorders such as epilepsy, multiple sclerosis, Parkinson's, or Alzheimer's diseases. Furthermore, there is a large body of evidence pointing out that CBD improves cognition, neurogenesis and presents anxiolytic, antidepressant, antipsychotic, and neuroprotective effects suggesting potential usefulness for the treatment of neuropsychiatric diseases and SUD. Here we review preclinical and clinical reports regarding the effects of CBD on the regulation of the reinforcing, motivational and withdrawal-related effects of different drugs of abuse such as alcohol, opioids (morphine, heroin), cannabinoids, nicotine, and psychostimulants (cocaine, amphetamine). Furthermore, a special section of the review is focused on the neurobiological mechanisms that might be underlying the 'anti-addictive' action of CBD through the regulation of dopaminergic, opioidergic, serotonergic, and endocannabinoid systems as well as hippocampal neurogenesis. The multimodal pharmacological profile described for CBD and the specific regulation of addictive behavior-related targets explains, at least in part, its therapeutic effects on the regulation of the reinforcing and motivational properties of different drugs of abuse. Moreover, the remarkable safety profile of CBD, its lack of reinforcing properties and the existence of approved medications containing this compound (Sativex®, Epidiolex®) increased the number of studies suggesting the potential of CBD as a therapeutic intervention for SUD. The rising number of publications with substantial results on the valuable therapeutic innovation of CBD for treating SUD, the undeniable need of new therapeutic agents to improve the clinical outcome of patients with SUD, and the upcoming clinical trials involving CBD endorse the relevance of this review.

Project description:IntroductionResearch has shown that eating disorder (ED) patients who abuse substances demonstrate worse ED symptomatology and poorer outcomes than those with EDs alone, including increased general medical complications and psychopathology, longer recovery times, poorer functional outcomes and higher relapse rates. This article provides a broad overview of the prevalence, aetiology, assessment and management of co-morbid EDs and substance use disorders (SUDs).ReviewThe co-occurrence of EDs and SUDs is high. The functional relationship between EDs and SUDs vary within and across ED subtypes, depends on the class of substance, and needs to be carefully assessed for each patient. Substances such as caffeine, tobacco, insulin, thyroid medications, stimulants or over the counter medications (laxatives, diuretics) may be used to aid weight loss and/or provide energy, and alcohol or psychoactive substances could be used for emotional regulation or as part of a pattern of impulsive behaviour. A key message conveyed in the current literature is the importance of screening and assessment for co-morbid SUDs and EDs in patients presenting with either disorder. There is a paucity of treatment studies on the management of co-occurring EDs and SUDs. Overall, the literature indicates that the ED and SUD should be addressed simultaneously using a multi-disciplinary approach. The need for medical stabilization, hospitalization or inpatient treatment needs to be assessed based on general medical and psychiatric considerations. Common features across therapeutic interventions include psycho-education about the aetiological commonalities, risks and sequelae of concurrent ED behaviours and substance abuse, dietary education and planning, cognitive challenging of eating disordered attitudes and beliefs, building of skills and coping mechanisms, addressing obstacles to improvement and the prevention of relapse. Emphasis should be placed on building a collaborative therapeutic relationship and avoiding power struggles. Cognitive behavioural therapy has been frequently used in the treatment of co-morbid EDs and SUDs, however there are no randomized controlled trials. More recently evidence has been found for the efficacy of dialectical behavioural therapy in reducing both ED and substance use behaviours.ConclusionFuture research would benefit from a meta-analysis of the current research in order to better understand the relationships between these two commonly co-occurring disorders.

Project description:AimsEating disorders (EDs) and substance use disorders (SUDs) often co-occur, and both involve somatic diseases. So far, no study has considered whether comorbid SUDs may impact somatic disease risk in patients with EDs. Therefore, this study aimed to examine the impact of comorbid SUDs on the risk of 11 somatic disease categories in patients with anorexia nervosa (AN), bulimia nervosa (BN) and unspecified eating disorder (USED) compared to matched controls.MethodsA retrospective cohort study was conducted using Danish nationwide registries. The study population included 20 759 patients with EDs and 83 036 controls matched on month and year of birth, sex and ethnicity. Hazard ratios (HRs) were calculated to compare the risk of being diagnosed with a somatic disease (within 11 categories defined by the ICD-10) following first ED diagnosis (index date) between ED patients and controls both with and without SUDs (alcohol, cannabis or hard drugs).ResultsThe ED cohort and matched controls were followed for 227 538 and 939 628 person-years, respectively. For ED patients with SUDs, the risk pattern for being diagnosed with different somatic diseases (relative to controls without SUDs) varied according to type of ED and SUD [adjusted HRs ranged from 0.95 (99% CI = 0.57; 1.59) to 4.17 (2.68, 6.47)]. The risk estimates observed among ED patients with SUDs were generally higher than those observed among ED patients without SUDs [adjusted HRs ranged from 1.08 (99% CI = 0.95, 1.22) to 2.56 (2.31, 2.84)]. Abuse of alcohol only had a non-synergistic effect on six disease categories in AN patients and five in BN and USED patients. Abuse of cannabis (with/without alcohol) had a non-synergistic effect on five disease categories in AN and BN patients and two in USED patients. Abuse of hard drugs (with/without alcohol or cannabis) had a non-synergistic effect on nine disease categories in AN patients, eight in BN patients and seven in USED patients.ConclusionsThe present study documents non-synergistic but not synergistic harmful somatic consequences of SUDs among patients with different EDs, with AN and hard drugs being the most predominant factors. Hence, EDs and SUDs did not interact and result in greater somatic disease risk than that caused by the independent effects. Since EDs and SUDs have independent effects on many somatic diseases, it is important to monitor and treat ED patients for SUD comorbidity to prevent exacerbated physical damage in this vulnerable population.

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Potential role of N-acetylcysteine in the management of substance use disorders.

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Potential role of N-acetylcysteine in the management of substance use disorders.

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