Anandamide

Lipidomics Gateway (25 January 2012) [doi:10.1038/lipidmaps.2012.1]

Acting on the endocannabinoid system, anandamide promotes feelings of well-being, in addition to mediating other central and peripheral effects.

The structure of anandamide (20:4, n-6; systematic name N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine). Visit anandamide in the LIPID MAPS structure database for more molecular information

Together with structurally similar 2-arachidonoylglycerol (2-AG), the fatty acyl N-arachidonoylethanolamine — more commonly known as anandamide — is a widely studied component of the endocannabinoid system. As an endogenous agonist of the G protein-coupled cannabinoid CB1 and CB2 receptors, anandamide has a three-dimensional structure that closely resembles Δ⁹-tetrahydrocannabinol, the primary psychoactive cannabinoid found in cannabis. Not surprisingly, therefore, anandamide similarly induces feelings of pleasure and well-being, its name being based on the Sanskrit word ananda, meaning 'bliss, delight' ¹ . Unlike Δ⁹-tetrahydrocannabinol, however, which is relatively stable, anandamide is degraded rapidly in the body, to free arachidonic acid and ethanolamine, by fatty acid amide hydrolase (FAAH), and therefore does not induce the long-lasting effects that are associated with cannabis use (and mis-use). Recently, anandamide and two other substances that inhibit its breakdown have also been found in chocolate, which might explain its appeal ² .

The long hydrocarbon tail of anandamide renders it minimally soluble in the hydrophilic extracellular matrix, meaning that its actions in the brain are local to its site of production and receptor localization ³ . Anandamide is generated from phospholipid precursors N-arachidonoylphosphatidylethanolamines, although the precise biosynthetic pathway is controversial ⁴ .

Arachidonoylphosphatidylethanolamines themselves are generated by the transfer of arachidonate from the sn-1 position of phospholipids to the nitrogen atom of phosphatidylethanolamines by a Ca²⁺-dependent acyltransferase. Information concerning the localization of this enzyme is likely to provide further insight into the synthesis and function of anandamide in the brain. Evidence currently supports the involvement of products of N-acylphosphatidylethanolamine-specific phospholipase D, which directly converts arachidonoylphosphatidylethanolamines into anandamide, as intracellular messengers, as anterograde modulators at postsynaptic CB1 and/or transient receptor potential vanilloid subtype 1 (TRPV1) receptors or in retrograde signalling ⁴ .

These actions of anandamide in the brain are likely to mediate its effects on memory, learning and control of movement, as well as modulating feeding behaviour, aspects of energy balance and pain perception ⁵ . In the periphery, anandamide acts on CB1 and CB2 receptors and TRPV1 receptors to modulate pain ⁶ and to regulate cardiovascular, gastrointestinal, immune and reproductive functions ⁵ . Consequently, efforts to increase endogenous levels of anandamide by inhibiting the rapid action of FAAH are the focus of several therapeutic approaches - for example, as new analgesic agents ⁶ and for the treatment of several types of cancer ³

Katrin Legg