Immunomodulating Activity of MDMA

MDMA (ecstasy) use produces neurochemical, behavioral, and endocrine changes similar to acute stress, acting as a chemical stressor. In rats, MDMA rapidly suppressed lymphocyte proliferation, decreased circulating lymphocytes, and increased plasma corticosterone. In humans, acute MDMA caused time-dependent immune dysfunction: CD4+ T-cells and lymphocyte responsiveness to stimulation decreased, while natural killer cells increased; total leukocyte count remained unchanged. Cortisol rose similarly to the rat model, suggesting MDMA triggers corticotrophin-releasing factor release from the hypothalamus, activating the HPA axis and sympathetic nervous system. These findings indicate MDMA ingestion may increase risk for immune system-related diseases.

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Abstract

Abstract 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.