Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties

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Abstract
HU211 is a novel synthetic derivative of tetrahydro-cannabinol (THC), the active marijuana ingredient. The stereochemistry of HU211 is enantiomeric to that of THC. In contrast to THC, HU211 is not psychotropic. This agent exhibits other types of biological activities; it is a non-competitive NMDA receptor blocker and has antinociceptive activity when injected with cupric chloride. This study examined its effects in autotomy, a behavioral model of neuropathic pain. Autotomy, a behavior of self-mutilation of denervated areas, was induced in Sabra rats by cutting the sciatic and saphenous nerves. We found that injections of HU211 (2.5 mg/kg) with cupric chloride (0.8 mg/kg) every 2nd day markedly suppressed autotomy during the injection period by delaying its average onset day and reducing the incidence of severe autotomy. Moreover, suppression of autotomy was retained in the postinjection period (for at least 30 days) but only when the drug was injected intraperitoneally. Lesser effects were achieved by subcutaneous injections. Cupric chloride or HU211 alone were ineffective. The general behavior and open field motor activity indicated that the effects of HU211 with Cu++ on autotomy were not due to sedation or ataxia but presumably due to antinociception mediated by NMDA receptor blockade.