A single baboon treated with MDMA (5 mg/kg twice daily for four days) showed large decreases in serotonin transporter binding in all brain regions when scanned with PET and a serotonin-specific tracer 13 to 40 days later. Reductions ranged from 44% in the pons to 89% in the occipital cortex. Tracers for dopamine transporters showed no changes. At 9 and 13 months, some brain regions partly recovered serotonin transporter levels while others, such as the neocortex, remained persistently low. These findings demonstrate that PET can detect MDMA-induced damage to serotonin neurons in living primates and suggest the method could be used to test whether human MDMA users experience similar neurotoxicity.
A new radioligand, [11C]-MBL, selectively binds to serotonin 5-HT2 receptors in the brain, as shown by in vitro assays (Ki = 0.5 nM) and PET imaging in baboons and seven healthy human volunteers. In humans, highest binding occurred in frontal, temporal, and parietal cortex, with lower levels in caudate and putamen. Blocking with ketanserin confirmed specificity. Frontal cortex-to-cerebellum ratios ranged from 1.7 to 2.7, with older volunteers showing lower ratios, suggesting age-related decline in 5-HT2 receptor density. [11C]-MBL enables in vivo monitoring of these receptors in most human brain regions.