The endocannabinoid system and the brain

Annu Rev Psychol. 2013:64:21-47. doi: 10.1146/annurev-psych-113011-143739. Epub 2012 Jul 12.


The psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), was isolated in the mid-1960s, but the cannabinoid receptors, CB1 and CB2, and the major endogenous cannabinoids (anandamide and 2-arachidonoyl glycerol) were identified only 20 to 25 years later. The cannabinoid system affects both central nervous system (CNS) and peripheral processes. In this review, we have tried to summarize research--with an emphasis on recent publications--on the actions of the endocannabinoid system on anxiety, depression, neurogenesis, reward, cognition, learning, and memory. The effects are at times biphasic--lower doses causing effects opposite to those seen at high doses. Recently, numerous endocannabinoid-like compounds have been identified in the brain. Only a few have been investigated for their CNS activity, and future investigations on their action may throw light on a wide spectrum of brain functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anxiety Disorders / drug therapy
  • Brain / drug effects*
  • Cannabinoids / chemistry
  • Cannabinoids / pharmacology
  • Cannabis / chemistry
  • Cognition / drug effects
  • Depressive Disorder / drug therapy
  • Dose-Response Relationship, Drug
  • Dronabinol / chemistry
  • Dronabinol / pharmacology
  • Endocannabinoids / pharmacology*
  • Humans
  • Learning / drug effects
  • Memory / drug effects
  • Neurogenesis / drug effects
  • Receptors, Cannabinoid / drug effects
  • Reward


  • Cannabinoids
  • Endocannabinoids
  • Receptors, Cannabinoid
  • Dronabinol