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 (<i>P</i> = 0.021). Urine benzoylecgonine concentration was lower in the mavoglurant-treated group versus placebo (<i>P</i> = 0.025); there was reduced alcohol consumption in the treatment group (<i>P</i> = 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.

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Journal
Science Translational Medicine
Published
2025-04-02
DOI
https://doi.org/10.1126/scitranslmed.adi4505
Citations
3
Primary Topic
Neurotransmitter Receptor Influence on Behavior
Type
article
Field-Weighted Citation Impact
2.73
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article

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

Marcus Herdener, Baltazar Gomez‐Mancilla, Nicole Pezous, Jang‐Ho Cha et al.
3 citations
Science Translational Medicine
Neurotransmitter Receptor Influence on Behavior
2.73
article

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

Marcus Herdener, Baltazar Gomez‐Mancilla, Nicole Pezous, Jang‐Ho Cha, Daniel Mosca, Kenneth M. Dürsteler, Marta Torrens, Bartolomé Pérez Gálvez, Ricardo Corral, Antoni Gual, Marc Vogel, Swati Dumitras, Enrique Kuper, Ricardo Dolmetsch, Fabrizio Gasparini, Ela Walker, Maria Berkheimer
article en
3 citations

Abstract

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 (<i>P</i> = 0.021). Urine benzoylecgonine concentration was lower in the mavoglurant-treated group versus placebo (<i>P</i> = 0.025); there was reduced alcohol consumption in the treatment group (<i>P</i> = 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.

Science Translational MedicineVol. 17(792)
Universitat de Miguel Hernández d'Elx (ES), Universitat de Vic - Universitat Central de Catalunya (ES), Novartis (Switzerland) (CH), Central Bank of Argentina (AR), Universitat Pompeu Fabra (ES), Universidad de Buenos Aires (AR), University Hospital of Basel (CH), Hospital Universitari Sant Joan D'Alacant (ES), University Hospital of Zurich (CH), Instituto Nacional de Rehabilitación Psicofísica (AR), Novartis (United States) (US), Kantonsspital Münsterlingen (CH), Hospital Del Mar (ES), Hospital del Mar Research Institute (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), University Psychiatric Hospital (SI)
Good health and well-being
Openalex Percentile: Top 11%
Neurotransmitter Receptor Influence on Behavior
2.73
DOISourceOpenAlex
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