Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for
cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of
dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating
cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive
dronabinol 20mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and
relapse prevention therapy.
Marijuana use was assessed using the timeline follow back method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (
dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in
marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on
dronabinol (77%), compared to placebo (61%) (P=.02), and
withdrawal symptoms were significantly lower on
dronabinol than placebo (P=.02). This is the first trial using an agonist substitution strategy for treatment of
cannabis dependence.
Dronabinol showed promise, it was well-tolerated, and improved treatment retention and
withdrawal symptoms. Future trials might test higher doses, combinations of
dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions.