Neural Effects of MDMA as Determined by Functional Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Awake Marmoset Monkeys

A recreational dose of MDMA (1 mg/kg) activates multiple brain regions in marmoset monkeys, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit (dorsal thalamus, sensory motor cortex, and basal ganglia). MDMA also activates the primary visual cortex and enhances the visual cortical response to light. The onset of brain activation matches the rise in plasma MDMA levels. A second study found that both low (4 × 1 mg/kg oral) and high (4 × 10 mg/kg intramuscular) MDMA doses reduce the NAA/creatine ratio in the hypothalamus, indicating vulnerability to damage. High doses also cause prolonged hyperthermia and reductions in serotonin and serotonin transporters in several brain areas, suggesting even recreational doses may have adverse consequences.

Study at a glance

Abstract

Abstract: We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of a recreational dose (1 mg/kg p.o.) of 3,4‐methylenedioxymethamphetamine (MDMA) on regional brain activity in awake, restrained marmoset monkeys. In a second study, magnetic resonance spectroscopy (MRS) and postmortem measurements of serotonin transporter (SERT) binding and serotonin (5‐HT) concentrations were used to determine the neurotoxic effects of low (4 × 1 mg/kg p.o.) and high (4 × 10 mg/kg i.m.) doses of MDMA. Several brain areas were significantly activated by the low oral dose of MDMA, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit composed of the dorsal thalamus, sensory motor cortex, and basal ganglia. MDMA activated the primary visual cortex under baseline conditions and also enhanced the visual cortical response to photic stimulation. The onset of brain activation correlated well with the rise in plasma MDMA concentrations measured in separate monkeys given the same drug treatment. In the second study, the ratio of N ‐acetylaspartate (NAA; a putative neuronal marker) to creatine was significantly reduced in the hypothalamus following either MDMA treatment regimen, suggesting a particular vulnerability of this structure to MDMA‐induced damage. Monkeys given the high‐dose regimen also showed prolonged hyperthermia and reductions in 5‐HT and SERT in a number of brain areas. These results are the first to identify the pattern of MDMA‐induced brain activation in a nonhuman primate model, and they further suggest that even recreational doses of MDMA may have adverse consequences as indicated by the reduced hypothalamic NAA/creatine ratio.