Immunomodulating activity of MDMA.
MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.
Pacifici
R
R
Clinical Biochemistry Department, Istituto Superiore di Sanità, Roma, Italy.
Zuccaro
P
P
Farré
M
M
Pichini
S
S
Di Carlo
S
S
Roset
P N
PN
Lopez
C H
CH
Ortuño
J
J
Segura
J
J
Camí
J
J
de la Torre
R
R
D000818:Animals; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D066298:In Vitro Techniques; D023421:Models, Animal; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine