Endocannabinoid membrane transporter (EMT)

Anandamide (N-arachidonoylethanolamine) is a key endocannabinoid that regulates various physiological processes by activating cannabinoid receptors (CB1 and CB2) [Piomelli, D., Nature Reviews Neuroscience, 2003]. The anandamide uptake/transport mechanism refers to the protein-mediated process that facilitates the movement of this lipophilic molecule from the extracellular space into the cytoplasm for degradation by fatty acid amide hydrolase (FAAH) [Fowler, C. J., FEBS Journal, 2013]. While the exact molecular identity of a single "anandamide transporter" remains a subject of scientific debate, several candidates have been identified, including fatty acid-binding proteins (FABPs) and the FAAH-like anandamide transporter (FLAT) [Kaczocha, M., et al., PNAS, 2009]. This mechanism is a validated therapeutic target because its inhibition increases local anandamide levels, enhancing endocannabinoid signaling in a site-specific and activity-dependent manner [Beltramo, M., et al., Science, 1997]. Drugs targeting this process, such as AM404 and UCM707, have shown potential in preclinical models for treating chronic pain, anxiety, and inflammatory conditions without the significant psychotropic effects associated with direct CB1 agonists [Nicolussi, S., & Gertsch, J., Trends in Pharmacological Sciences, 2015].

Other names

Anandamide transporterAEA transporterEndocannabinoid uptake systemPutative anandamide transporter

Inhibition of the cellular uptake of anandamide from the extracellular space into the cytoplasm, thereby increasing its availability to activate cannabinoid receptors.