[8] The discovery of this receptor helped provide a molecular explanation for the established effects of cannabinoids on the immune system.

[17] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration.

[19] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG activates the MAPK-ERK pathway, while noladin inhibits adenylyl cyclase.

[15] Northern blot analysis further indicates the expression of the CNR2 gene in immune tissues,[10] where they are primarily responsible for mediating cytokine release.

[33] Application of CB2-specific antagonists has found that these receptors are also involved in mediating analgesic effects in the peripheral nervous system.

However, these receptors are not expressed by nociceptive sensory neurons, and at present are believed to exist on an undetermined, non-neuronal cell.

[6] Through their inhibition of adenylyl cyclase via their Gi/Goα subunits, CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP).

[15] Although the exact role of the cAMP cascade in the regulation of immune responses is currently under debate, laboratories have previously demonstrated that inhibition of adenylyl cyclase by CB2 receptor agonists results in a reduction in the binding of transcription factor CREB (cAMP response element-binding protein) to DNA.

[37] Consistent with these findings are studies that demonstrate increased CB2 receptor expression in the spinal cord, dorsal root ganglion, and activated microglia in the rodent neuropathic pain model, as well as on human hepatocellular carcinoma tumor samples.

A study using knock-out mice found that CB2 receptor is essential for the maintenance of both MZ B cells and their precursor T2-MZP, though not their development.

Without the receptor, there was an undesirable spike in the blood concentration of MZ B lineage cells and a significant reduction in the production of IgM.

[39][40] Specifically, the CB2 agonist JWH-015 was shown to induce macrophages to remove native beta-amyloid protein from frozen human tissues.

[41] In patients with Alzheimer's disease, beta-amyloid proteins form aggregates known as senile plaques, which disrupt neural functioning.

[42] Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[43] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer.