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Vol. 296, Issue 1, 207-215, January 2001

Acute Effects of 3,4-Methylenedioxymethamphetamine Alone and in Combination with Ethanol on the Immune System in Humans

Roberta Pacifici, Piergiorgio Zuccaro, Candido Hernández López, Simona Pichini, Simonetta Di Carlo, Magi Farré , Pere Nolasc Roset , Jordi Ortuño, Jordi Segura and Rafael de La Torre

Clinical Biochemistry Department, Istituto Superiore di Sanità, Roma, Italy (R.P., P.Z., S.P., S.D.C.); and Pharmacology Unit, Institut Municipal d'Investigació Mèdica (IMIM) (C.H.L., M.F., P.N.R., J.O., J.S., R.d.L.T.), Universitat Autònoma de Barcelona (M.F., P.N.R., R.d.L.T.) and Universitat Pompeu Fabra (J.S.), Barcelona, Spain

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval 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 stimulation 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 increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma ) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

0022-3565/01/2961-0207$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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