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 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.
Pacifici
R
R
Clinical Biochemistry Department, Istituto Superiore di Sanità, Roma, Italy.
Zuccaro
P
P
Hernandez López
C
C
Pichini
S
S
Di Carlo
S
S
Farré
M
M
Roset
P N
PN
Ortuño
J
J
Segura
J
J
Torre
R L
RL
D000328:Adult; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006213:Hallucinogens / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007107:Immune System / Q000187:drug effects*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D010641:Phenotype
D016207:Cytokines; D006213:Hallucinogens; D000431:Ethanol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D006854:Hydrocortisone