Effects of marijuana on macrophage function.

Abstract

Delta-9-tetrahydrocannabinol (THC) is the major psychoactive component of marijuana. This substance has been shown to elicit a spectrum of effects in vitro and in experimental animals. The drug decreases host resistance to viruses (1–3) and bacteria (1), alters cellular morphology and function (4–10), and inhibits RNA, DNA, and protein synthesis (11–13). These effects on macromolecular synthesis suggest that THC may elicit its immunosuppressive effects by altering the expression and/or secretion of effector molecules. Macrophages play a central role in the regulation of immune responsiveness. These cells act “early” in a primary viral infection by exerting intrinsic and extrinsic antiviral activities (17,18), and play a central role in host resistance by their capacity to produce interferons and monokines and to function as antigen-presenting cells (19,20). Responsive macrophages undergo a multi-step process to full activation (21–23). Each of these stages in the activation process is associated with discrete functional activities. Responsive macrophages ingest and degrade bacteria and viruses. A hallmark of fully activated macrophages, on the other hand, is their capacity to destroy tumor cells and virus-infected cells. These effector functions are induced in response to a variety of signals, including bacteria and bacterial cell wall products (i.e., lipopolysaccharide). The sequential development of responsive macrophages to full activation is accompanied by the expression of defined, quantifiable protein markers which reflect the potential of the macrophage to execute different functional activities.