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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics January 2001, 296 (1) 207-215;
Roberta Pacifici
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Piergiorgio Zuccaro
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Candido Hernández López
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Simona Pichini
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Simonetta Di Carlo
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Magi Farré
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Pere Nolasc Roset
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Jordi Ortuño
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Jordi Segura
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Rafael de La Torre
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Abstract

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-β and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-γ) 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.

Footnotes

  • Send reprint requests to: Dr. Rafael de la Torre, Pharmacology Unit, Institut Municipal d'InvestigacióMèdica (IMIM), Doctor Aiguader 80, E-08003 Barcelona, Spain. E-mail: rtorre{at}imim.es

  • This investigation was supported by the Department of Social Affair (Italy) and Fondo de Investigaciones Sanitarias 97/1198, Fondo de Investigaciones Sanitarias 98/0181, Comisio Interdepartamental de Recerca I Innovacio Tecnologica-SGR 99-242, and Plan Nacional Sobre Drogas (Spain).

  • Abbreviations:
    MDMA
    3,4-methylenedioxymethamphetamine
    NK
    natural killer cell
    HPA
    hypothalamic-pituitary-adrenal axis
    PHA
    phytohemagglutinin
    Th1
    T-1 helper lymphocyte (refers to a CD4-subtype cell)
    IL
    interleukin
    IFNγ
    interferon-γ
    TNF
    tumor necrosis factor
    Th2
    T-2 helper lymphocyte (refers to a CD4-subtype cell)
    TGFβ1
    transforming growth factor-β1
    PE
    phycoerythrin
    FITC
    fluorescein isothiocyanate
    AUC
    area under the curve
    • Received June 23, 2000.
    • Accepted September 19, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 296 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 296, Issue 1
1 Jan 2001
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics January 1, 2001, 296 (1) 207-215;

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics January 1, 2001, 296 (1) 207-215;
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