Risks and Mechanisms in Addiction Neuroscience Informing Treatment

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropsychiatry".

Deadline for manuscript submissions: 15 October 2026 | Viewed by 1749

Special Issue Editor


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Guest Editor
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60654, USA
Interests: addiction; traumatic brain injury; psychiatry

Special Issue Information

Dear Colleagues,

Tremendous advances have been made in our understanding of addiction cycle neurocircuitry. These advances have propelled further research into mechanisms and risk in addiction neuroscience, informing novel treatment development; this Special Issue aims to highlight this research.

We are looking for cutting-edge research on novel risks and mechanisms which may inform treatment, such as co-occurring conditions that confer addiction risk (e.g., traumatic brain injury), neuromodulatory treatments (e.g., transcranial magnetic stimulation), novel therapeutic plastogens (e.g., psychedelics), exercise treatment interventions (e.g., yoga) and endocrine system approaches (e.g., GLP-1 receptor agonists)

We welcome original research reports, scoping reviews, systematic reviews and meta-analyses.

Dr. Amy A. Herrold
Guest Editor

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Keywords

  • substance use disorders
  • risk
  • mechanism
  • neuromodulation
  • psychedelic
  • GLP-1

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Published Papers (2 papers)

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Research

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17 pages, 1175 KB  
Article
Effects of a Single Sub-Anesthetic Dose of Ketamine in Tobacco Use Disorder: An Active-Placebo, Randomized Crossover Study
by Nathan R. Luzum, Marcia H. McCall, Charlotte Talley Boyd, Heather Columbano, Edward Ip, Santiago Saldana, Alison H. Oliveto and Merideth Addicott
Brain Sci. 2026, 16(5), 496; https://doi.org/10.3390/brainsci16050496 - 30 Apr 2026
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Abstract
Background/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine’s therapeutic potential for tobacco use is unknown. Here, we investigated a single [...] Read more.
Background/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine’s therapeutic potential for tobacco use is unknown. Here, we investigated a single sub-anesthetic dose among adults with tobacco use disorder who were not interested in changing their smoking behavior. Methods: Utilizing a randomized, within-subject crossover, double-blinded, counter-balanced, midazolam-controlled design, participants (n = 18) received a 0.71 mg/kg infusion of ketamine and a 0.025 mg/kg infusion of midazolam (i.e., active placebo) at least two weeks apart. Participants were asked to abstain from smoking after the infusions until the post-infusion sessions, 1 day following infusion, where participants completed measures of smoking behavior, craving, and withdrawal symptoms. Participants continued to record their smoking behavior over the 7 days following infusion. Participants also completed a semi-structured qualitative interview regarding their experiences. Results: Compared to midazolam, ketamine infusion led to a non-significant reduction (p = 0.10, ηp2 = 0.153) in the number of cigarettes smoked during the requested abstinence period. Following this period, there were no significant differences in ad lib smoking. Ketamine showed no effect on craving or withdrawal symptoms. Participants reported more intense psychological experiences following ketamine infusion (p < 0.001, ηp2 = 0.830) and about half reported it felt easier to abstain from smoking after the ketamine infusion. Conclusions: While well tolerated, these findings suggest ketamine has little to no direct effect on quantitative measures of cigarette smoking, craving, or withdrawal. However, the qualitative measures suggest ketamine improves mood and reduces craving in some individuals for several days. Future studies should investigate whether ketamine can indirectly support smoking cessation among individuals with comorbid psychiatric indications for ketamine treatment. Full article
(This article belongs to the Special Issue Risks and Mechanisms in Addiction Neuroscience Informing Treatment)
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Review

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17 pages, 994 KB  
Review
MAC/MAB–RCS: An Integrative Regulatory Control Framework for Risk Stratification and Personalized Intervention in Addiction Psychiatry
by Anna Makarewicz, Remigiusz Recław, Anna Grzywacz, Jolanta Chmielowiec and Krzysztof Chmielowiec
Brain Sci. 2026, 16(2), 187; https://doi.org/10.3390/brainsci16020187 - 3 Feb 2026
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Abstract
Objectives: Addiction disorders remain a major challenge in contemporary psychiatry due to high relapse rates and significant individual and societal burden. Despite advances in addiction neurobiology, current diagnostic frameworks and dominant models offer limited tools for early risk identification and dynamic support of [...] Read more.
Objectives: Addiction disorders remain a major challenge in contemporary psychiatry due to high relapse rates and significant individual and societal burden. Despite advances in addiction neurobiology, current diagnostic frameworks and dominant models offer limited tools for early risk identification and dynamic support of clinical decision-making across the course of treatment. The aim of this narrative review is to introduce the MAC/MAB–RCS model as an integrated conceptual framework for risk stratification and personalized intervention in addiction psychiatry. Methods: The proposed model integrates evidence from four complementary domains: genetic, epigenetic, and stress-axis biomarkers; functional brain network organization; and psychological/psychiatric dimensions relevant to addictive behaviors. These domains are synthesized into a unified conceptual structure designed to capture dynamic regulatory processes underlying addiction vulnerability. Results: At the core of the model lies the Regulatory Control State (RCS), a latent higher-order construct representing an individual’s dynamic regulatory capacity through the integration of cognitive control, emotional regulation, and motivational drive modulation. Disruption of the RCS is conceptualized as a shared transdiagnostic mechanism driving craving escalation, compulsive behavior, and relapse vulnerability, independent of substance class or specific addictive behavior. Conclusions: The MAC/MAB–RCS model aligns with the principles of precision psychiatry by offering a pragmatic, clinically oriented translational framework with potential applicability across clinical settings, bridging neurobiological research and clinical practice. The review discusses its relationship to existing models, potential clinical and systemic applications, key limitations, and priorities for future validation studies. Full article
(This article belongs to the Special Issue Risks and Mechanisms in Addiction Neuroscience Informing Treatment)
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