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

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.

Hematological, immunological and neurochemical effects of chronic amphetamine treatment in male rats

“…B cells are main mediators in the humoral immune response but they also are important antigen-presenting cells for exogenous proteins. Our present results suggest that chronic AMPH severely compromised humoral immune responses against both T-dependent and T-independent antigens, and could explain the enhanced vulnerability to several infectious diseases observed in drug addicts (1,3). Antibodies are the main adaptative mechanism of defence against bacterial infections, and also play an important role in the defence against other types of pathogens.…”

“…Lymphopenia as well as the increase in circulating granulocyte number, granulocytosis, have been also found in mice following chronically injecting AMPH (10), in rats following MDMA administration (5), in both laboratory animals and humans MDMA consumers (3) and in rats following acute AMPH administration (12). However no difference neither in total leukocyte count nor the percentage of T-lymphocytes in AMPHtreated animals was observed by other authors (1).…”

“…One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently increase susceptibility to infectious disease (3,11). AMPH and several of its derivatives, as methylenedioxymethamphetamine (MDMA, "ecstasy") and methylenedioxyamphetamine (MDA) have been reported to act as potent immunosuppressor, however data are contradictory as some authors suggest that AMPH and its derivaties could enhace the immune system response (12).…”

“…Besides of well known addictive properties, amphetamine was found to influence the immune functions as a potent immunosuppressor. Although addiction to AMPH is a serious social and medical problem, however the data concerning AMPH -immune system interactions are still limited and the precise mechanism of this interaction is still not fully understood (3).…”

3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

“…It has been reported that MDMA increases susceptibility to infectious diseases in humans [13,14,15] and in laboratory animals [16,17]. Moreover, MDMA was shown to suppress the generation of lipopolysaccharide-induced proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1β [18,19] and to increase the lipopolysaccharide-induced production of the anti-inflammatory cytokine IL-10 [20].…”