Cell‐Mediated Immune Response in MDMA Users After Repeated Dose Administration

Repeated use of MDMA ('ecstasy') causes time-dependent immune dysfunction similar to a single dose, but the second dose extends the period of impaired immunocompetence. The drug decreases CD4 T-helper cells, increases natural killer (NK) cells, and reduces lymphocyte responsiveness to stimulation. In poor metabolizers, MDMA accumulation produces greater immunomodulatory effects, including significant differences in NK cell function. Recreational MDMA users show long-term alterations: reduced lymphocytes, T cells, and CD4 cells (though within normal limits), and NK cells reduced to one-third of healthy levels. Over two years, a subgroup showed statistically significant decreases in immune parameters, potentially increasing susceptibility to infection and immune disorders.

Study at a glance

Abstract

A bstract : Acute administration of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) produces time‐dependent immune dysfunction in humans. Recreational use of MDMA generally includes repeated drug consumption, often in association with other drugs, such as alcohol and cannabis. In the laboratory setting, repeated MDMA administration to healthy MDMA consumers produced a time‐dependent immune dysfunction similar to that observed with the ingestion of a single dose, and the first of the two administrations paralleled the time‐course of MDMA‐induced cortisol stimulation kinetics and MDMA plasma concentrations. A significant decrease in CD4 T‐helper cells with simultaneous increase in natural killer (NK) cell and a decrease in functional responsiveness of lymphocytes to mitogenic stimulation was observed. Response to the second dose was either long‐lasting compared with the first dose or disproportionate and did not show any parallelism with cortisol and MDMA plasma concentrations. This circumstance extended the critical period during which immunocompetence is highly impaired as a result of MDMA use. Accumulation of MDMA in the body of a poor metabolizer induced higher immunomodulatory effects with statistically significant differences in NK cell function compared with extensive metabolizers. When basal values of lymphocyte subsets were examined in a population of recreational MDMA users participating in different clinical trials, alterations in several immunological parameters were observed. The absolute number of lymphocytes, in particular T lymphocytes and CD4 T‐helper cell subsets, showed a trend toward reduced values, although cell counts were within normal limits. By contrast, NK cells in MDMA consumers were reduced to one‐third of those from healthy persons. A statistically significant decrease in affected immune parameters was recorded during a 2‐year observation period in a subgroup of recreational MDMA users. These permanent alterations in immunologic homeostasis may result in impairment of general health and subsequent increased susceptibility to infection and immune‐related disorders.