DEPENDENCE ON DELTA(9)-TETRAHYDROCANNABINOL - STUDIES ON PRECIPITATEDAND ABRUPT WITHDRAWAL

A cannabinoid antagonist, SR 141716A, dose dependently precipitated a behavioral withdrawal syndrome in rats continuously infused i.p. for o nly 4 days with relatively low-dose regimens of Delta(9)-tetrahydrocan nabinol. The following dose regimens, expressed as mg/kg/24 hr, were u sed for days 1 through 4: high-12.5, 25, 50 and 100; medium-2.5, 5, 10 and 20; and low-0.5, 1, 2 and 4. The major withdrawal signs of the sy ndrome were scratching, rubbing face with paws, licking, wet-dog shake s, arched back and ptosis (at least 50% closure of eyelids). At the hi ghest dose regimen, other signs noted in fewer subjects were biting, t ongue rolling, retropulsion, head shakes, extended limbs or high stepp ing, ataxia, myoclonic spasms and front paw treading. During abrupt wi thdrawal (Delta(9)-tetrahydrocannabinol was discontinued and vehicle s ubstituted) abstinence signs were also noted; however, except during a 48-hr observation period, withdrawal was not sufficiently robust to a chieve statistical significance. The results of this study provide evi dence that a modest course of Delta(9)-tetrahydrocannabinol can produc e physical dependence. Hence, the risk and incidence of marijuana depe ndence in humans may be greater than previously projected.