Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans

Cell-mediated immune response and release of cytokines after the administra tion of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in co mbination with ethanol were assessed in a double blind, randomized, crossov er, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interv al between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested . Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stim ulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous incre ase in natural killer (NK) cells. Ethanol consumption produced a decrease i n T-helper cells and B lymphocytes. The combination of MDMA and ethanol cau sed the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cyt okines (transforming growth factor-beta and interleukin-10) and a switch fr om Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cyto kines (interleukin-4 and interleukin-10). Disregulation in the production o f pro- and anti-inflammatory cytokines with an unbalance toward anti-inflam matory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immu nological homeostasis, if temporarily repeated, might alter the immune resp onse with a risk for the general health status.