Gosset Anandamide transporter Overview
The term "Anandamide transporter/reuptake mechanism" refers to the hypothesized process by which the endocannabinoid anandamide (arachidonoylethanolamide, AEA) is rapidly removed from the synaptic cleft and transferred into cells for degradation by fatty acid amide hydrolase (FAAH)[1][3][6]. Early studies proposed that a specific, high-affinity, sodium-independent transporter facilitates this uptake[3]. However, substantial debate remains over whether a unique membrane-spanning transporter exists or whether anandamide crosses membranes primarily by passive diffusion, with its removal driven by rapid intracellular hydrolysis and potential intracellular carriers (fatty acid binding proteins, FABPs)[4][5]. Several small molecules can modulate anandamide uptake, some of which may exert their effects by acting on yet unidentified protein components or by perturbing membrane dynamics[2][8]. The absence of a molecularly defined target means that "Anandamide transporter" is not currently an accepted therapeutic target class but remains an area of investigation, especially for indirect modulation of endocannabinoid signaling. The precise biological and disease roles attributed to this mechanism are, therefore, largely speculative and related to broader endocannabinoid system function[1][3][8][4][5].
Mechanism of Action
Inhibition of anandamide reuptake (by uptake inhibitors like AM404, OMDM-1, O-2093, etc.) and elevation of extracellular anandamide levels.
Biological Functions
Disease Associations
Safety Considerations
- Off-target effects (since no molecular target is conclusively identified)
- Unintended modulation of endocannabinoid system
- Potential impact on cognition, mood, and pain sensitivity