AN ANALGESIA CIRCUIT ACTIVATED BY CANNABINOIDS

Although many anecdotal reports indicate that marijuana and its active constituent, delta-9-tetrahydrocannabinol (delta-9-THC), may reduce p ain sensation(1,2), studies of humans have produced inconsistent resul ts(3-6). In animal studies, the apparent pain-suppressing effects of d elta-9-THC and other cannabinoid drugs(7-12) are confounded by motor d eficits(13,14). Here we show that a brainstem circuit that contributes to the pain-suppressing effects of morphine(15) is also required for the analgesic effects of cannabinoids. Inactivation of the rostral ven tromedial medulla (RVM) prevents the analgesia but not the motor defic its produced by systemically administered cannabinoids, Furthermore, c annabinoids produce analgesia by modulating RVM neuronal activity in a manner similar to, but pharmacologically dissociable from, that of mo rphine. We also show that endogenous cannabinoids tonically regulate p ain thresholds in part through the modulation of RVM neuronal activity . These results show that analgesia produced by cannabinoids and opioi ds involves similar brainstem circuitry and that cannabinoids are inde ed centrally acting analgesics with a new mechanism of action.