Results from controlled human laboratory studies suggest that CB1 receptor antagonists, should they again become available for clinical use, might be effective treatment for cannabis intoxication and that oral THC (perhaps combined with an α-adrenergic agonist such as lofexidine) might be effective treatment for cannabis withdrawal. For the treatment of cannabis dependence, there is little data to guide the clinician, as few controlled clinical trials have been conducted. Only buspirone has shown efficacy in such a trial, while atomoxetine, bupropion, divalproex, and nefazadone have not. A few small open-label clinical trials suggest that the COMT inhibitor entacapone, dronabinol, and lithium may warrant further study, although this recommendation is tempered by the weakness of evidence from open-label studies. In contrast, available evidence from human laboratory studies suggests that the mu-opioid receptor antagonist naltrexone may increase the abuse liability of cannabis and therefore should not be used for treatment. Recent pre-clinical studies suggest the potential of FAAH inhibitors such as URB597 for the treatment of cannabis withdrawal and of endocannabinoid-metabolizing enzymes andnicotinic alpha7 receptor antagonists such as methyllycaconitine (MLA) for treatment of cannabis dependence.
