Chronic administration of morphine provokes generation of antibodies to morphine and immunosuppression in individuals with opioid use disorder.

Globally, opioid use disorder (OUD) presents a significant public health challenge linked to high mortality and disability rates. Heroin and other morphine derivatives are prevalent among abused opioids. Prolonged exposure to these substances in individuals with OUD can trigger an immune response, leading to the production of antibodies to morphine that may bind to morphine and potentially mitigate its rewarding effects. In our study, we analyzed serum samples from patients diagnosed with OUD to explore the nature and properties of antibodies to morphine, aiming to characterize the generation of antibodies to morphine due to long-term exposure to morphine. We observed varying titers of antibodies to morphine in OUD patients, absent in healthy controls, with both free morphine and morphine complexes detected bound to these antibodies, indicating less potency. Furthermore, our analysis revealed elevated levels of FoxP3, a critical transcription factor in regulatory T-cells (Tregs) responsible for maintaining immunosuppression. Concurrently, reduced levels of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) indicated immunosuppressive activity. Notably, decreased antibody titers against the Acr1 protein of Mycobacterium tuberculosis suggested that morphine-induced immune suppression might compromise responses to other pathogens. These findings indicate that chronic morphine exposure not only suppresses host immunity but also induces the production of antibodies to morphine. Investigating whether these antibodies contribute to immune suppression or can be harnessed to combat morphine dependence presents an intriguing avenue for future research.