Monoacylglycerol lipase (MAGL)

Monoacylglycerol lipase, or MAGL, is the main enzyme that breaks down the endocannabinoid 2-arachidonoylglycerol, controlling how long its signal lasts.

MAGL sits on the sending side of synapses, near the CB1 receptors that 2-AG activates, and splits the molecule into glycerol and arachidonic acid. It accounts for most 2-AG breakdown in the brain, with a smaller share handled by the enzymes ABHD6 and ABHD12. The arachidonic acid it releases is a raw material for prostaglandins, so MAGL links the endocannabinoid system to classic inflammatory chemistry, and in the brain it supplies much of the arachidonic acid used for that purpose.

Experimental MAGL inhibitors raise 2-AG and have been examined in animals for pain and inflammation, but sustained blockade leads CB1 receptors to desensitize and produce tolerance, which has complicated drug development. The term appears in advanced writing on endocannabinoid tone. CBD has no established direct effect on MAGL, and any clinical relevance of the enzyme to CBD remains investigational.