The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including
modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act
as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not
exclusively CB1 receptors) and in the periphery (primarily but not exclusively CB2 receptors) are only
partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids
(phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods,
have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use
of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking),
as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially
cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the
treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide
the reader with the foundational basic and clinical science linking the endocannabinoid system and the
phytocannabinoids with their potentially therapeutic role in the management of chronic pain.
