Methylenedioxymethamphetamine (MDMA, 'Ecstasy'): a stressor on the immune system

Abstract

Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; 'Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a 'chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed.

Figures

Figure 1

An illustration of the chemical structures of (a) amphetamine and methamphetamine, both of which stimulate catecholamine release in the central nervous system (CNS), and (b) MDA, methylenedioxymethamphetamine (MDMA), MDEA and fenfluramine; substituted amphetamines, all of which are potent releasers of serotonin.

Figure 2

A diagrammatic summary of the effect of in vivo administration of methylenedioxymethamphetamine (MDMA) on aspects of innate and adaptive immunity.

Figure 3

A schematic diagram depicting the potential of methylenedioxymethamphetamine (MDMA)-induced increases in interleukin-10 (IL-10) production to interfere with antigen presentation, and thereby produce anergy in the immune system.

Figure 3

A schematic diagram depicting the potential of methylenedioxymethamphetamine (MDMA)-induced increases in interleukin-10 (IL-10) production to interfere with antigen presentation, and thereby produce anergy in the immune system.

Figure 4

A schematic diagram outlining potential central and peripheral mediators of methylenedioxymethamphetamine (MDMA)-induced immunosuppression.