Acute ingestion of MDMA (ecstasy) causes a transient marked increase in serotonin and dopamine at central synapses. Recent studies demonstrated that MDMA induces damage of serotonergic nerve terminals and alters hippocampal processing. Pronounced cognitive deficits in MDMA users affect learning and memory abilities. This pattern of predominant and long-lasting memory dysfunction suggests that the functioning of the hippocampus might be affected by the neurotoxic effects of MDMA. We present the case of a 16-year-old girl who developed an acute organic and psychotic syndrome caused by occasional use of low to moderate dose of MDMA. Serial neuroimaging ((18)F-FDG-PET and brain MRI) were correlated with her neurocognitive performance and clinical evolution. The structural and metabolic changes correlated with a severe cognitive impairment. After 16 months of intensive neuropsychological rehabilitation she showed significant improvement in hippocampal-related memory cognitive functions, which correlated with normalization of her (18)F-FDG-PET and remarkable hippocampal remodelling. This case report indicates that even non-chronic MDMA use may cause subacute toxic encephalopathy in which the clinical evolution is paralleled by neuroimaging changes in specific cerebral areas. The most relevant aspect is the reversibility of the volumetric changes, which may be the structural correlate of an ongoing hippocampal remodelling.