Lancet Diabetes Endocrinol

Cannabinoid receptor targeting agent yields significant weight loss in metabolic syndrome trial

October 17, 2025

Monlunabant, a novel cannabinoid receptor 1 (CB1R) inverse agonist, demonstrated robust weight loss across all doses, but tolerability issues—especially at higher doses—may limit its clinical utility.

Study details: This 16-week, double-blind, randomized, placebo-controlled phase 2a trial (NCT05891834) enrolled 243 adults with obesity and metabolic syndrome at 25 Canadian centers. Participants received once-daily oral monlunabant (10 mg, 20 mg, or 50 mg) or placebo. Primary endpoint was mean bodyweight change from baseline at week 16 vs. placebo.

Results: All monlunabant doses led to statistically significant and clinically meaningful weight loss compared with placebo: least squares mean differences were -6.4 kg (10 mg), -6.9 kg (20 mg), and -8.0 kg (50 mg). Adverse events, mainly mild to moderate GI and psychiatric symptoms, were dose-dependent and led to higher withdrawal rates at increased doses (up to 42% at 50 mg).

Source:

Knop FK, et al; trial investigators. (2025, September 29). Lancet Diabetes Endocrinol. Efficacy and safety of monlunabant in adults with obesity and metabolic syndrome: a double-blind, randomised, placebo-controlled, phase 2a trial. https://pubmed.ncbi.nlm.nih.gov/41038215/