A Double-Blind, Randomized, Controlled Pilot Trial of &lt;em&gt;N&lt;/em&gt;-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders

Back, Sudie E.; McCauley, Jenna L.; Korte, Kristina J.; Grös, Daniel F.; Leavitt, Virginia; Gray, Kevin M.; Hamner, Mark B.; DeSantis, Stacia M.; Malcolm, Robert; Brady, Kathleen T.; Kalivas, Peter W.

doi:10.4088/jcp.15m10239

Cited by 72 publications

(64 citation statements)

References 42 publications

(36 reference statements)

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“…This effect persisted for 4 weeks after stopping NAC. Subjects also reported improvements in CAPS scores of PTSD symptoms and CAPS intrusive thoughts score …”

Section: Drug Cue–induced Neuroplasticitymentioning

confidence: 93%

The neurobiology of addiction

Uhl

Koob

Cable³

2019

Annals of the New York Academy of Sciences

151

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Substance and alcohol use disorders impose large health and economic burdens on individuals, families, communities, and society. Neither prevention nor treatment efforts are effective in all individuals. Results are often modest. Advances in neuroscience and addiction research have helped to describe the neurobiological changes that occur when a person transitions from recreational substance use to a substance use disorder or addiction. Understanding both the drivers and consequences of substance use in vulnerable populations, including those whose brains are still maturing, has revealed behavioral and biological characteristics that can increase risks of addiction. These findings are particularly timely, as law‐ and policymakers are tasked to reverse the ongoing opioid epidemic, as more states legalize marijuana, as new products including electronic cigarettes and newly designed abused substances enter the legal and illegal markets, and as “deaths of despair” from alcohol and drug misuse continue.

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“…This effect persisted for 4 weeks after stopping NAC. Subjects also reported improvements in CAPS scores of PTSD symptoms and CAPS intrusive thoughts score …”

Section: Drug Cue–induced Neuroplasticitymentioning

confidence: 93%

The neurobiology of addiction

Uhl

Koob

Cable³

2019

Annals of the New York Academy of Sciences

151

View full text Add to dashboard Cite

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“…Another clinical trial assessed the effects N-acetylcysteine (vs placebo) in combination with cognitive-behavioral therapy on post-traumatic stress disorder symptomology and substance abuse (i.e., alcohol use disorder or cocaine use disorder) among 35 dual-diagnosed veterans (Back et al, 2016). The investigators found that active N-acetylcysteine maintenance (2,400 mg/day for eight weeks) significantly reduced drug craving and depression, although no medication effects on drug-taking behavior were found.…”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

Glial and neuroinflammatory targets for treating substance use disorders

Bachtell

Jones

Heinzerling

et al. 2017

Drug and Alcohol Dependence

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Background The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. Methods Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. Results Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. Conclusions The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

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“…Likewise, a chronic unpredictable stress rat model of depression markedly downregulates EAAT2 and EAAT3 in the hippocampus ( Zhu et al, 2017 ). Also, acute stress in rats causes an enduring reduction of GLT-1 in the NAc ( Garcia-Keller et al, 2016 ), and a recent double-blind clinical trial in veterans comorbid for posttraumatic stress disorder and substance use disorder revealed that NAC reduced both drug craving and symptoms of posttraumatic stress disorder ( Back et al, 2016 ). Sub-anesthetic ketamine, an off-label treatment for refractory depression increasingly used in the clinic, rescued this deficit and the associated behavior ( Zhu et al, 2017 ).…”

Section: Perspectivesmentioning

confidence: 99%

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Spencer

Kalivas

2017

International Journal of Neuropsychopharmacology

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Drug addiction has often been described as a “hijacking” of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past 20 years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior. Much of this research focuses on the role played by ionotropic glutamate receptors directly involved in long-term potentiation and depression or metabotropic receptors indirectly modulating synaptic plasticity. Importantly, the balance between glutamate release and clearance tightly regulates the patterned activation of these glutamate receptors, emphasizing an important role for glutamate transporters in maintaining extracellular glutamate levels. Five excitatory amino acid transporters participate in active glutamate reuptake. Recent evidence suggests that these glutamate transporters can be modulated by chronic drug use at a variety of levels. In this review, we synopsize the evidence and mechanisms associated with drug-induced dysregulation of glutamate transport. We then summarize the preclinical and clinical data suggesting that glutamate transporters offer an effective target for the treatment of drug addiction. In particular, we focus on the role that altered glutamate transporters have in causing drug cues and contexts to develop an intrusive quality that guides maladaptive drug seeking behaviors.

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A Double-Blind, Randomized, Controlled Pilot Trial of <em>N</em>-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders

Cited by 72 publications

References 42 publications

The neurobiology of addiction

The neurobiology of addiction

Glial and neuroinflammatory targets for treating substance use disorders

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

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