Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by in¯ammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice de®cient in the cannabinoid receptor CB1 tolerate in¯ammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide signi®cant neuroprotection from the consequences of in¯ammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.