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Because selective activation of peripheral cannabinoid (CB2) receptors in rat C-6 glioma cells has been shown to induce apoptosis through enhanced ceramide synthesis de novo, CB2 agonists present potential as anti glioma agents. KM 233 is a δ8-tetrahydrocannabinol analog with a dimethyl substitution that exhibits high binding affinity for both the CB1 and CB2 receptors with 13-fold selectivity for the CB2 receptor (Kis = 12.3 and 0.91 nM, respectively). Demonstrating good lipophilicity and ability to penetrate the blood brain barrier, KM 233 inhibits human U87 glioma cell proliferation in vitro with an IC50 value of 1.4 μM and significantly reduces U87 glioma tumor size in vivo at a dose of 2 mg/kg in a SCID mouse xenograft side-pocket model.

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