Cannabinoids protect cells from oxidative cell death: A receptor-independent mechanism

Serum is required for the survival and growth of most animal cells. In seru m-free medium, B lymphoblastoid cells and fibroblasts die after 2 days. We report that submicromolar concentrations of Delta(9)-tetrahydrocannabinol ( THC), Delta(8)-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, preve nted serum-deprived cell death, Delta(9)-THC also synergized with platelet- derived growth factor in activating resting NIH 3T3 fibroblasts. The cannab inoids' growth supportive effect did not correlate with their ability to bi nd to known cannabinoid receptors and showed no stereoselectivity, suggesti ng a nonreceptor-mediated pathway. Direct measurement of oxidative stress r evealed that cannabinoids prevented serum-deprived cell death by antioxidat ion. The antioxidative property of cannabinoids was confirmed by their abil ity to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol. Therefore, cannabinoids act as antioxidants to mo dulate cell survival and growth of B lymphocytes and fibroblasts.