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Substitution therapy with synthetic tetrahydrocannabinol (THC) has inconsistent effects in cannabis withdrawal (e.g., NEJM JW Psychiatry Apr 2018 and PLoS One 2018; 13:e0190768), and no other medications have been approved for this indication. In a phase IIa, 4-week trial, researchers tested the efficacy of a non–FDA-approved enzyme inhibitor (PF-04457845), which increases brain endocannabinoid concentrations, in 70 cannabis-dependent men using a mean of 3 joints daily (ever tried to quit, 84%; use ≥500 days, 94%).
Participants were admitted to an inpatient unit for 1 week to precipitate withdrawal and to be randomized to 4 mg of PF-04457845 or placebo; after week 1, they received outpatient treatment for 3 weeks. The medication group had fe…