“CB(2) cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. CB(2) receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with the lack of CB(2) receptors in the normal CNS…
We have demonstrated that antinociception produced by CB2 receptor-selective agonists may be mediated by stimulation of β-endorphin release from CB2-expressing cells. The β-endorphin released thus appears to act at μ-opioid receptors, probably on the terminals of primary afferent neurons, to produce peripheral antinociception. This mechanism allows for the local release of endogenous opioids limited to sites where CB2 receptors are present, thereby leading to anatomical specificity of opioid effects. In this way, CB2 receptor activation may produce peripheral antinociception without CNS side effects.”
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