Efficacy of minocycline in substance use disorder: A systematic review of preclinical and clinical studies.

Addiction is a serious condition that leads to negative changes in the central nervous system. Although there have been significant advancements in medication treatments for substance use disorders (SUDs), it is clear that there is a need to implement these developments in clinical settings to explore new therapeutic approaches for helping individuals with SUDs. Minocycline, a semi-synthetic second-generation tetracycline, possesses neuroprotective and anti-inflammatory properties. Recent studies have shown promising results when using this drug for the treatment of substance misuse. This study aimed to review the pre-clinical and clinical studies assessing the therapeutic efficacy of minocycline on drug-related outcomes, including reward, tolerance, withdrawal, impairments, and toxicity. We conducted a systematic review to assess the effectiveness of minocycline in ameliorating drug-induced outcomes per the PRISMA guidelines. Electronic medical databases Web of Science, PubMed/Medline, Scopus, and Google Scholar were searched from databases from their inception date until December 2023. 56 of the 623 articles met the eligible criteria for analysis. Of the 56 articles reviewed, 51 were conducted on animals, while 5 involved human subjects. Our study indicates that the majority of animal studies have primarily focused on morphine and alcohol, with no research found to date on the effects of cannabis. This review highlights minocycline's potential in addiction treatment through its effects on anti-inflammatory mechanisms, neuroprotection, regulation of synaptic plasticity. Results of this study suggest that although minocycline shows promise in experiments, its effectiveness in humans may be limited by dosage, individual variability, and addiction's complexity. Further clinical studies are required to clarify the optimal dose, duration of administration, and delivery route and focus on identifying specific conditions where it may be most effective.