Substance abuse and inflammation: consequences beyond the brain.

Substance use disorders are traditionally conceptualized as disorders of brain reward circuitry; however, accumulating evidence demonstrates that addictive substances exert profound and persistent effects on central and peripheral immune and inflammatory systems. Opioids, psychostimulants, alcohol, nicotine, cannabinoids, and psychedelics modulate immune signaling across multiple organs, including the brain, gut, liver, lungs, skin, and systemic circulation. In parallel, drugs of abuse remodel neuroimmune communication both centrally and peripherally, altering interactions between neurons, glial cells, and immune populations. This review synthesizes clinical and preclinical evidence linking substance exposure to systemic inflammation, delineates shared cellular and molecular mechanisms across tissues, and highlights emerging paradigms of systemic neuroimmune crosstalk.