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Review
. 2024 May;25(7):867-884.
doi: 10.1080/14656566.2024.2360653. Epub 2024 May 31.

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
Affiliations
Review

Promising immunomodulators for management of substance and alcohol use disorders

Amanda M Acuña et al. Expert Opin Pharmacother. 2024 May.

Abstract

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 disorder; alcohol use disorder; cannabidiol; dexmedetomidine; ibudilast; minocycline; pioglitazone; probenecid.

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Conflict of interest statement

Declaration of Interests

The authors have no relevant affiliations of financial involvement with organization or entity with financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

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MeSH terms

Substances