PET imaging of the endocannabinoid system

The endocannabinoid system consists of cannabinoid receptors (which mediate the actions of cannabis), their endogenous ligands (endocannabinoids), and the enzymes and proteins associated with their regulation. In brain, the endocannabinoid system, in part, functions to modulate the release of other neurotransmitters via the subtype 1 (CB₁) receptor. Abnormalities of CB₁ receptor expression or endocannabinoid transmission have been associated with several neuropsychiatric diseases. Subtype 2 (CB₂) receptors are found primarily on immune and neuroimmune cells, and are overexpressed in activated microglia and neuroinflammation. Both receptors are of particular interest for biomarker development and therapeutic targets. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are responsible for the breakdown of endocannabinoids. Growing evidence supports the regulation of endocannabinoids as involved in neuropsychiatric and neuroinflammatory diseases. However, the function of endocannabinoid system components in vivo remains difficult to assess. Therefore, the use of functional imaging techniques, such as positron-emission tomography (PET), may be particularly useful in the assessment and quantification of the endocannabinoid system. This review covers the current understanding of PET imaging that directly targets the endocannabinoid system.