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Pacifici R, Pichini S, Zuccaro P, Farre M, Segura M, Ortuno J, Di Carlo S, Bacosi A, Roset P, Segura J, De La Torre R. 
“Paroxetine Inhibits Acute Effects of MDMA on the Immune System in Humans”. 
J Pharmacol Exp Ther. 2004 Jan 13.
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 of paroxetine (or placebo) for the three 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 antiinflammatory cytokines (transforming growth factor-beta and interleukin-10) with a simultaneous decrease of antiinflammatory response (interleukin-2) was also observed. Pretreatment with paroxetine partially reduced MDMA effects on CD4 T and NK cells, while 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 hours. 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.
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