Cannabinoids and morphine differentially affect HIV-1 expression in CD4⁺ lymphocyte and microglial cell cultures

The influence of substances of abuse on the progression of HIV-1 infection is controversial, and pharmacologic factors have been postulated as a potential explanation for conflicting data arising from epidemiological studies and animal models. In the present study, cell culture models of HIV-1 infection were used to test this hypothesis. The synthetic cannabinoid WIN 55,212-2 was found to potently inhibit HIV-1 expression in a concentration- and time-dependent manner in CD4⁺ lymphocyte and microglial cell cultures. In sharp contrast, morphine either inhibited or stimulated viral expression, depending upon the time of drug exposure, and marked differences were observed between CD4⁺ and microglial cells. Also, WIN 55,212-2 inhibited the stimulatory effect of morphine in HIV-1 infected CD4⁺ cells. These in vitro findings support the notion that pharmacologic factors need to be considered in epidemiological studies and animal models that pertain to HIV-1 infection.