Cannabinoid CB1/CB2 receptors (agonist)

Class

Cannabinoid receptor agonist (THC:CBD combination)

Pathway

Endocannabinoid system modulation (used for MS-related spasticity)

Notes

original target text: Cannabinoid CB1/CB2 receptors | original target text: Cannabinoid CB1/CB2 receptors (agonist)

The endocannabinoid system consists of two G protein-coupled receptors, CB1 and CB2, and their endogenous lipid ligands, anandamide and 2-arachidonoylglycerol. CB1 is expressed densely in the central nervous system, particularly on presynaptic neurons, where its activation dampens release of neurotransmitters such as glutamate and GABA; CB2 is found mainly on immune cells and modulates inflammatory signaling. Pharmacological activation of these receptors can reduce muscle tone, pain perception, and neuroinflammation, which is why cannabinoid agonists have been explored for spasticity associated with multiple sclerosis, chronic pain, and certain inflammatory conditions.

Botanical extracts combining two principal cannabis constituents, tetrahydrocannabinol (THC) and cannabidiol (CBD), illustrate a rationale beyond single-compound dosing: THC is a partial agonist at CB1 that provides much of the antispasticity and analgesic activity, whereas CBD has low direct affinity for CB1/CB2 but modulates THC's effects and acts on other receptor systems, tempering some of the psychoactive and sedative consequences of CB1 activation. This combination approach aims to preserve therapeutic benefit while adjusting the side-effect profile relative to THC alone, a consideration central to spasticity management where dosing tolerability determines usability.