Mechanisms of endocannabinoid transport in the brain

Br J Pharmacol. 2022 Sep;179(17):4300-4310. doi: 10.1111/bph.15469. Epub 2021 May 27.

Abstract

The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide are among the best studied lipid messengers in the brain. By activating cannabinoid receptors in the CNS, endocannabinoids tune synaptic function, thereby influencing a variety of physiological and behavioural processes. Extensive research conducted over the last few decades has considerably enhanced our understanding of the molecular mechanisms and physiological functions of the endocannabinoid system. It is now well-established that endocannabinoids are synthesized by postsynaptic neurons and serve as retrograde messengers that suppress neurotransmitter release at central synapses. While the detailed mechanisms by which endocannabinoids gate synaptic function and behavioural processes are relatively well characterized, the mechanisms governing endocannabinoid transport at central synapses remain ill defined. Recently, several studies have begun to unravel the mechanisms governing intracellular and intercellular endocannabinoid transport. In this review, we will focus on new advances in the mechanisms of intracellular and synaptic endocannabinoid transport in the CNS. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Keywords: 2-arachidonoylglycerol; FABP; endocannabinoid; endocannabinoid transport; fatty acid binding protein; synapse.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain
  • Cannabinoid Receptor Modulators
  • Endocannabinoids*
  • Receptors, Cannabinoid
  • Synapses
  • Synaptic Transmission*

Substances

  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptors, Cannabinoid