Cannabis use is increasing worldwide despite the various health effects of this substance.We report two cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/day).In both male patients, acute encephalitis was suspected. Brain MRI diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological and MRI acute abnormalities improved within weeks. New exposition to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later.Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.