TY - JOUR T1 - Dependence on delta 9-tetrahydrocannabinol: studies on precipitated and abrupt withdrawal. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1290 LP - 1295 VL - 278 IS - 3 AU - M D Aceto AU - S M Scates AU - J A Lowe AU - B R Martin Y1 - 1996/09/01 UR - http://jpet.aspetjournals.org/content/278/3/1290.abstract N2 - A cannabinoid antagonist, SR 141716A, dose dependently precipitated a behavioral withdrawal syndrome in rats continuously infused i.p. for only 4 days with relatively low-dose regimens of delta 9-tetrahydrocannabinol. The following dose regimens, expressed as mg/kg/24 hr, were used 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 syndrome were scratching, rubbing face with paws, licking, wetdog shakes, arched back and ptosis (at least 50% closure of eyelids). At the highest dose regimen, other signs noted in fewer subjects were biting, tongue rolling, retropulsion, head shakes, extended limbs or high stepping, ataxia, myoclonic spasms and front paw treading. During abrupt withdrawal (delta 9 tetrahydrocannabinol was discontinued and vehicle substituted) abstinence signs were also noted; however, except during a 48-hr observation period, withdrawal was not sufficiently robust to achieve statistical significance. The results of this study provide evidence that a modest course of delta 9-tetrahydrocannabinol can produce physical dependence. Hence, the risk and incidence of marijuana dependence in humans may be greater than previously projected. ER -