title: Paroxetine inhibits acute effects of 3,4-methylenedioxymethamphetamine on the immune system in humans.
abstract: The effect of pretreatment with paroxetine on cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") was investigated in a double-blind, randomized, crossover, controlled clinical trial in which 12 healthy male recreational users of MDMA participated. Subjects received 20 mg/day paroxetine (or placebo) for the 3 days before MDMA challenge (100 mg). Acute MDMA administration produced a time-dependent decrease in CD4 T-helper cells, a decrease in the functional responsiveness of lymphocytes to mitogenic stimulation, a simultaneous increase in natural killer (NK) cells as well as cortisol and prolactin stimulation kinetics. A high increase in the release of anti-inflammatory cytokines (transforming growth factor-beta and interleukin-10) with a simultaneous decrease of anti-inflammatory response (interleukin-2) was also observed. Pretreatment with paroxetine partially reduced MDMA effects on CD4 T and NK cells, whereas totally inhibiting the suppression of the immune response to mitogens and alterations in cytokines release. MDMA-induced alterations in the immune system as well as antagonistic effects mediated by paroxetine show a trend toward baseline levels at 24 h. These findings suggest that acute effects of MDMA on immune system are mainly mediated by its interaction with the serotonin transporter and subsequent serotonin release with a possible participation of other neuroendocrine regulatory systems.
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pacifici
authors.forename: Simona
authors.initials: S
authors.lastname: Pichini
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Zuccaro
authors.forename: Magí
authors.initials: M
authors.lastname: Farré
authors.forename: Mireia
authors.initials: M
authors.lastname: Segura
authors.forename: Jordi
authors.initials: J
authors.lastname: Ortuño
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Carlo
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacosi
authors.forename: Pere N
authors.initials: PN
authors.lastname: Roset
authors.forename: Jordi
authors.initials: J
authors.lastname: Segura
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017374:Paroxetine / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors