**Abstract**

Opiate receptor (uOR) is expressed in central nervous system, gastrointestinal tract, male and female reproductive tissues, and immune cells. Morphine, a ligand for opioid receptor family, is known to activate the hypothalamic-pituitary-adrenal axis and release immunosuppressive glucocorticoids. Herein we present that minor changes, in the form of nonsynonymous single nucleotide polymorphisms, in μOR have cumulative impact on receptor-mediated signaling and functions of specific cell type(s). Significant reduction was seen in cells in M and S phases with coactivation of immune receptors with μOR. Flow cytometry-based experiments established a reduction in B and T lymphocytes, NK cells, and macrophages. Differences in types of immune cells were found to be significant to reduce immune response(s) mounted by GG(mutant allele)-bearing individuals. This is the first report on cross-talk between LPS-binding and μOR, explaining the reduction in the number of T and B cells after chronic opiate use and also the association of this impact on immunocytes with functional SNP, rs1799972/118G allele of OPRM1 gene as an explanation for the immune suppression in opiate users. Initially present lower cell titers can be further lowered by exogenous opiates and account for immunosuppression seen in chronic opiate users or after long-term treatment with opiate drugs for chronic pain.

**Keywords:** immune response activation, costimulation, cellular activation, opioid receptors
