Brain MDMA and MDA was measured in two ecstasy-related fatalities with monoclonal antibodies that recognize MDMA and MDA, using signal amplification staining with horseradish peroxidase (HRP). The investigators examined post-mortem samples from two 23-year old men with MDMA or "amphetamine compounds" detectable in blood after death. Death in one case, discovered 28 h after death, was most probably acute cardiac failure after consuming MDMA, cocaine, alcohol and other drugs, and the other death, discovered approximately three days post-mortem, was probably caused by disseminated intravascular coagulation (DIC) after acute hyperthermia. The researchers examined tissue from all four brain lobes (frontal, temporal, parietal, occipital), basal ganglia, hippocampus, thalamus, hypothalamus, pons, cerebellar vermis, medulla oblongata and pituitary collected from two fatalities wherein MDMA was detected in blood. The same immunohistochemical procedures were performed on six control samples, taken from four women (age at death 27-32), all murdered by stabbing or gunshot, and two men (age at death 17-26), one murdered by gunshot and one killed in a traffic accident. Interval between death and autopsy in controls ranged from 28 to 91 h. Staining only appeared in the two ecstasy-related cases, and not in controls, (except very weak cytoplasmic staining in parietal cortex and cerebellar vermis). In the ecstasy-related fatalities, staining produced a diffuse cytoplasmic staining of the perikaryon, though sometimes axons and dendrites were also visualized. Strong reactivity appeared in all four cortical lobes, in caudate, thalamus, lentiform nucleus, cerebellar vermis, mammillary bodies, hypothalamus and hippocampus. Staining was weak in the pons and medulla. The researchers examined antibody specificity, and found that only pure MDMA and MDA, and not PMA or amphetamine, produced negative immunoreactivity (abolished staining or reduced it to background levels). MDMA was found in white matter and gray matter in cortex, with values in white matter being somewhat lower than gray matter in Case 1 and higher in Case 2. Some pituitary cells were stained, particularly the acidophilus, probably because of their being more active than other cell types in the pituitary. Overall, study findings indicate that MDMA can be detected in post-mortem brain tissue and that it can be found throughout the brain, including gray and white matter. The authors interpret detectable levels of MDMA in pituitary as in accordance with findings of acute MDMA-induced neuroendocrine effects in humans, such as increased cortisol (see, for example, Grob et al. 1996; Harris et al. 2002; Mas et al. 1999; Vollenweider et al. 1998). The results suggest that MDMA is taken up and widely distributed throughout the brain after ingestion. However, changes in the brain after death might also be responsible for the distribution seen in these samples.