Promising immunomodulators for management of substance and alcohol use disorders
Amanda M Acuña 1, Connor Park 2, Jonna M Leyrer-Jackson 2, M Foster Olive 1
1Department of Psychology, Behavioral Neuroscience and Comparative Psychology Area, Arizona State University, Tempe, Arizona, USA.
2Department of Medical Education, Creighton University School of Medicine – Phoenix Campus, Phoenix, Arizona, USA.
Affiliationer
Introduction
The neuroimmune system has emerged as a novel target for the treatment of substance use disorders (SUDs), with immunomodulation producing encouraging therapeutic benefits in both preclinical and clinical settings.
Areas covered
In this review, we describe the mechanism of action and immune response to methamphetamine, opioids, cocaine, and alcohol. We then discuss off-label use of immunomodulators as adjunctive therapeutics in the treatment of neuropsychiatric disorders, demonstrating their potential efficacy in affective and behavioral disorders. We then discuss in detail the mechanism of action and recent findings regarding the use of ibudilast, minocycline, probenecid, dexmedetomidine, pioglitazone, and cannabidiol to treat (SUDs). These immunomodulators are currently being investigated in clinical trials described herein, specifically for their potential to decrease substance use, withdrawal severity, central and peripheral inflammation, comorbid neuropsychiatric disorder symptomology, as well as their ability to improve cognitive outcomes.
Expert opinion
We argue that although mixed, findings from recent preclinical and clinical studies underscore the potential benefit of immunomodulation in the treatment of the behavioral, cognitive, and inflammatory processes that underlie compulsive substance use.
KEYWORDS: Substance use disorderalcohol use disorderibudilastminocyclineprobeneciddexmedetomidinepioglitazonecannabidiol
Article highlights
Use of cocaine, methamphetamine, opioids, cocaine, and alcohol produces a wide range of dynamic changes in immune system function
Immune system alterations are also found in patients with various non-substance related neuropsychiatric conditions, which have a high degree of co-morbidity with SUDs
In animal models of SUDs, ibudilast, minocycline, probenecid, pioglitazone, and cannabidol have been shown to reduce drug self-administration, relapse-like behaviors, or withdrawal symptoms related to methamphetamine, alcohol, and opioids
Clinical studies in human patients have shown that ibudilast can attenuate opioid withdrawal symptoms and alcohol craving and consumption
Clear clinical benefits of minocycline, probenecid, demedetomidine, pioglitazone or cannabidol on substance use, craving, or withdrawal have not yet been established
Numerous clinical trials of these immunomodulators for SUDs are still on-going
