A stabilized CBDA derivative reduced weight and improved metabolism in obese and genetically obese mice

EPM301 (40 mg/kg/day) produced weight loss, increased physical activity, and improved glycemic and lipid profiles in diet-induced obese mice. It also reduced body weight and overeating in Magel2-null mice (a Prader-Willi syndrome model), and when given preventively, completely blocked weight gain.

In vivo study testing EPM301 (a stabilized CBDA-O-methyl ester derivative) in two mouse models: diet-induced obesity (DIO) with high-fat diet and genetic-induced obesity (GIO) using Magel2-null mice, a model for Prader-Willi syndrome. Doses of 20 and 40 mg/kg/day administered intraperitoneally.

CBDA is unstable and converts to CBD, limiting its therapeutic use. This stabilized derivative showed anti-obesity effects in two distinct obesity models, suggesting potential for both common and rare forms of obesity.

Prader-Willi syndrome has very limited treatment options, and the finding that a cannabis-derived compound could prevent weight gain in this genetic model opens a new therapeutic avenue. The stabilization of CBDA also represents a pharmaceutical advance.

Animal study only. Intraperitoneal administration does not reflect typical human drug delivery. Long-term safety unknown. The Magel2-null mouse model does not perfectly replicate human Prader-Willi syndrome. No human trials yet.