Long-term effects of 'ecstasy' abuse on the human brain studied by FDG PET

The popular recreational drug, 'ecstasy', mainly contains 3,4-methylenediox ymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of cau sing neurotoxic lesions to the serotonergic system as demonstrated by anima l studies, examinations of human cerebrospinal fluid, and the first positro n emission tomography (PET) studies using the serotonin transporter ligand [C-11]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[F-18]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an inde x of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected nu mber of brain regions. FDG uptake was normalized in each individual by divi ding local FDG uptake by the maximum FDG uptake in the individual's brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at th e time of PET scanning, and age at first ecstasy use, respectively. Normali zed FDG uptake was reduced within the striatum and amygdala of ecstasy user s when compared to controls. No statistically significant correlation of th e FDG uptake and the cumulative dose of ecstasy was detected. A positive co rrelation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG up take in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in Former ecstasy users who did no t consume ecstasy for more than 1 year. FDG uptake was significantly more a ffected in ecstasy users who started to consume ecstasy before the age of 1 8 years. In conclusion, ecstasy abuse causes long-lasting effects on glucos e metabolism in the human brain. These effects are more severe in the case of very early abuse. However, several questions still remain to be answered , i.e. the correlation of the neuronal alterations and the history of ecsta sy use (cumulative dose, and time since the last dose) and its reversibilit y. ((C) 2001 Lippincott Williams & Wilkins).