Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity.

Significant advances are being made towards understanding the genetic basis for spinal neurodegenerative diseases, however, effective pharmacotherapy remains elusive. One of the primary theories underlying neuron vulnerability is susceptibility to excitotoxicity. We present for the first time evidence that the activation of the CB(1) cannabinoid receptor effectively modulates kainate toxicity in primary neuronal cultures prepared from mouse spinal cord. Addition of Delta(9)-tetrahydrocannabinol to the culture medium attenuated the toxicity produced by kainate. The CB(1) receptors were localized to spinal neurons and astrocytes. The neuroprotective effect was blocked with the CB(1) receptor antagonist, SR141716A, indicating a receptor-mediated effect.