Evaluating remyelination compounds for new applications in opioid use disorder management.

Opioid use disorder (OUD) is associated with a reduction in brain white matter, affecting critical areas involved in decision-making, impulse control, and reward processing. The FDA has approved several drugs and natural compounds that enhance myelination, targeting oligodendrocyte progenitor cells (OPCs), directly enhancing oligodendrocyte (OL) function, or acting as cofactors for myelin production. This retrospective case study aimed to assess whether current clinical evidence supports the use of myelin-enhancing agents to promote remission in OUD. We evaluated a range of compounds with demonstrated effects on myelination, including muscarinic antagonists, cholesterol and lipid homeostatic agents, anti-aging drugs, immunomodulatory agents, anti-inflammatory medications, and others (25 medications in total), as well as 17 vitamins and supplements. Buprenorphine and methadone were used as positive controls. Sequential analyses were performed to identify individual drugs driving significant changes in remission rates ( ≤ 0.01;  ≥ 3,000) and their effects across age, sex, and Body Mass Index (BMI) categories. Three key findings emerged: (1) melatonin improved remission rates in males but showed no effect in females; (2) ibuprofen significantly increased remission rates, particularly in individuals aged 20-39 and 40-59 years; and (3) thiamin was associated with decreased remission rates in males and individuals with a BMI ranging from normal weight to obese. Additionally, buprenorphine and methadone were confirmed as effective in promoting remission. These findings highlight the importance of personalized medicine in treating OUD and suggest that further research is needed to explore individualized treatment strategies based on sex, age, and BMI.