Mavoglurant reduces cocaine use in patients with cocaine use disorder in a phase 2 clinical trial

Metabotropic glutamate receptor 5 (mGluR5) is involved in cocaine reward processing and addiction. Preclinical studies suggest that blocking this receptor inhibits cocaine self-administration and seeking behavior in rodents. We assessed a selective noncompetitive antagonist of mGluR5 called mavoglurant in a phase 2 randomized, placebo-controlled clinical trial of 68 adults with cocaine use disorder. Study participants were randomly assigned in a 1:1 ratio to an up-titrating schedule of oral mavoglurant twice daily up to 200 mg for 98 days or placebo. The primary end point was the proportion of cocaine use days over the treatment period assessed by a retrospective self-report using Timeline Followback. Secondary end points were urine analysis of the cocaine metabolite benzoylecgonine and alcohol use measured by Timeline Followback assessment. Exploratory end points included testing for cocaine and alcohol metabolites in hair samples. The posterior probability of mavoglurant reducing cocaine use at the end of treatment was ≥99.0% for a treatment difference <0 and ≥36.6% for a treatment difference <-10%. The difference between mavoglurant and placebo was also assessed using analysis of covariance (P = 0.021). Urine benzoylecgonine concentration was lower in the mavoglurant-treated group versus placebo (P = 0.025); there was reduced alcohol consumption in the treatment group (P = 0.072). Seventy-six percent (randomized set) and 79% (safety analysis set) of patients completed the final treatment visit. Adverse events in the treatment group were headache, dizziness, and nausea. In this small and short trial, mavoglurant reduced cocaine and alcohol use in patients with chronic cocaine use disorder.