A shared pathology among many neurological and neurodegenerative disorders is neuronal loss. Cannabinoids have been shown to be neuroprotective in multiple systems. However, both agonists and antagonists of the CB 1 cannabinoid receptor are neuroprotective, but the mechanisms responsible for these actions remain unclear. Recently a CB 1 receptor interacting protein, CRIP1a, was identified and found to alter CB 1 activity. Here we show that in an assay of glutamate neurotoxicity in primary neuronal cortical cultures CRIP1a disrupts agonist-induced neuroprotection and confers antagonist-induced neuroprotection. © 2011 Elsevier Ireland Ltd.