# Identification of a Possible Endocannabinoid-Mediated Mechanism of Action of Cetylated Fatty Acids

## TL;DR

This paper suggests that cetylated fatty acids may work by boosting endocannabinoids, offering a new way to treat musculoskeletal pain and inflammation.

## Contribution

The paper is the first to show that cetylated fatty acids may act via monoacylglycerol lipase inhibition.

## Key findings

- Cetylated fatty acids inhibit monoacylglycerol lipase, increasing endocannabinoids locally.
- This mechanism may explain their analgesic and anti-inflammatory effects in musculoskeletal conditions.
- The findings open new avenues for developing indirect cannabinoid-based analgesics.

## Abstract

Some musculoskeletal disorders, including osteoarthritis; arthrosis; post-traumatic injuries; and other inflammatory tendon, joint and muscular afflictions, still represent unmet medical needs. Cetylated fatty acids (CFAs) are key components of widely distributed over-the-counter products, especially for topical use, which are intended to reduce symptoms associated with these conditions. Nevertheless, the mechanism of action of CFAs’ analgesic and anti-inflammatory properties has not yet been clearly established. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), are known to produce analgesic and anti-inflammatory effects. These compounds undergo physiological inactivation operated by several enzymes, including monoacylglycerol lipase (MAGL). We herein demonstrate for the first time that the therapeutic effects of CFAs may be attributable, at least in part, to their MAGL inhibition activities, which induce a local increase in analgesic/anti-inflammatory endocannabinoids in close proximity to the site of administration. These findings pave the way for the development of new potent local analgesic agents, whose action is based on an indirect cannabinoid effect.