A contemporary view of MDMA

Abstract

Several years of pre-clinical and clinical research specify that MDMA (a principal ingredient in the drug known as “ecstasy”) is neurotoxic to serotonergic nerve terminals, and these neurobiological changes have been predicted to account for neurocognitive deficits, depression, and anxiety seen in human users. In 2002, a high-profile scientific report presented evidence that acute MDMA exposure caused significant damage to dopamine neurons in nonhuman primates (Ricaurte et al. 2002). The finding received considerable media attention, and gave the public the impression that MDMA was far more hazardous than originally thought. Less than a year later, the authors conceded that they were unable to replicate or extend their findings, and this was attributed to the fact that methamphetamine, not MDMA, was used in the earlier experiment (Ricaurte et al. 2003). Critics heralded the mix-up as the tip of an iceberg of a larger scientific/government coalition with an agenda to push forward the War on Drugs. The battle cry went out that “the US research agency that supports research on drug abuse needs to ensure its independence from intense political pressure to prove that recreational drugs are harmful” (Nature 2003), and a claim was made that NIDA favors “studies that are liable to prove the toxicity of recreational drugs” (Knight 2003). As expected, this issue provided fodder for individuals and organizations that would like a major revamping of MDMA research efforts. As a result, a debate on the actual harms of MDMA use was ignited with questions on whether MDMA is neurotoxic at all (Morris 2003). In the following year, Rich De La Garza and Ron Cowan organized a mini-symposium for the annual meeting of the Society for Neuroscience with the intent of providing the essential facts of neurotoxicity and neurocognitive changes that result from MDMA exposure in humans and animals. The current special issue is one outcome of that presentation and the contributions include original investigations as well as reviews that provide a critical analysis of published data pointing out strengths and weaknesses of established findings and frequently used methodologies. The special issue begins with the elegant and comprehensive work of Baumann and colleagues who show that typical doses of MDMA causing long-term serotonin (5-HT) depletion in rats do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA administration induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. A review article by De La Garza and colleagues reveals that MDMA serves as a reinforcer in rats (as measured in intravenous self-administration assays), though the responses are not of similar frequency relative to those previously reported for other psychostimulants (e.g., cocaine). Kuhn and colleagues report sex-specific differences in locomotor effects produced by MDMA. Female rats exhibit greater behavioral activation than males after MDMA treatment initially and upon challenge after a 2-week recovery period. The mechanism by which MDMA increases locomotor activity more in females is attributed to Psychopharmacology (2007) 189:403–405 DOI 10.1007/s00213-006-0636-4