A synthetic CBDA derivative (EPM301) reduced body weight, improved blood sugar and lipid profiles, and reversed liver damage in both diet-induced and genetically obese mice.
Researchers interested in cannabinoid-based approaches to obesity and metabolic disorders.
Preventive treatment completely blocked weight gain in genetic obesity model
What the researchers found
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.
Why it matters
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.
The numbers in context
40 mg/kg/day dose used for DIO mice; 20 and 40 mg/kg/day for GIO mice. Preventive treatment completely inhibited weight gain in standard-diet-fed Magel2-null mice.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
Promising preclinical results in two obesity models, but no human data yet.
When this study was published
Published in 2022.
The bigger picture
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.
Questions still open
- Would EPM301 work in humans? What is the mechanism of action (the study does not specify receptor targets)? How does this compare to existing anti-obesity medications?
Common questions
What is CBDA and how does it differ from CBD?
What is Prader-Willi syndrome?
Read the original research
The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity.
International journal of molecular sciences, 23(10)
Citation
Ben-Cnaan, Elad; Permyakova, Anna; Azar, Shahar; Hirsch, Shira; Baraghithy, Saja; Hinden, Liad; Tam, Joseph. (2022). The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity.. International journal of molecular sciences, 23(10). https://doi.org/10.3390/ijms23105610
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