Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial

Dakwar, Elias; Mahony, Amy; Choi, C. Jean; Pavlicova, Martina; Brooks, Daniel; Mariani, John P.; Levin, Frances R.

Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control. Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs. Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management. Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F-1,F-86 = 8.74, p = .004; in dollars: F-1,F-86 = 16.67, p < .0001) and cannabis using days (F-1,F-86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X-1(2) = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence. Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.