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

Amphetamine derivative MDMA (Ecstasy) suppresses the immune system, reducing neutrophil phagocytosis, lowering production of pro-inflammatory cytokines TNF-α and IL-1β, and increasing the immunosuppressive cytokine IL-10. It also decreases circulating lymphocyte numbers—especially CD4+ T cells—and impairs T-cell function by reducing mitogen-stimulated proliferation and skewing cytokine production toward a Th2 response. These effects are largely indirect, caused by release of endogenous immunomodulatory substances rather than direct action on immune cells. The physiological changes resemble those of acute stress, suggesting MDMA acts as a chemical stressor on immunity, potentially increasing infection risk for users.

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Abstract

Summary 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‐α (TNF‐α) and interleukin (IL)‐1β, 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.