Anandamide: From modulation of neuronal excitation to antimicrobial activities—What is in common?

Anandamide (N-arachidonoyl ethanolamine; AEA) is an endocannabinoid produced by neurons and immune cells, where it is synthesized on demand from membrane phospholipids. It functions as a neuromodulator by being released from postsynaptic neurons upon excitation and acting in a retrograde direction to inhibit further neurotransmitter release from presynaptic neurons by binding to the CB1 cannabinoid receptor. AEA also binds directly to various ion channels in mammals resulting in either activation or inhibition of transmembrane current with the implications thereof. In addition, AEA has immunomodulatory activities and is involved in the communication of the microbiota-gut-brain axis (MGBA). AEA can alter the composition of the gut microbiota and attenuate inflammatory diseases of the gastrointestinal tract. AEA also has antibacterial and antibiofilm activities against Gram-positive bacteria and antifungal activities against Candida albicans. Some of the mechanisms involved in the antimicrobial activities of AEA resemble those involved in neuromodulation, and understanding the latter assists in apprehending the former. In this chapter, we provide an initial description of the biosynthesis and degradation of AEA, followed by a presentation of its numerous receptors in humans and the consequences of their activation. Thereafter, its modulations of the immune system and gut microbiota are discussed, with a conclusion on the mechanisms involved in its antibacterial and antifungal activities.