It is not true, as some advertisements have it, that cannabidiol (CBD) ‘boosts’ or ‘balances’ the immune system. But it is immunomodulatory. More precisely, it is immune-suppressive and anti-inflammatory, acting on cytokines such as TNF-α, IFN-γ, IL-6, IL-1β, IL-2, IL-17A, and chemokines, such as CCL-2. Overall its mechanism is to suppress target cells, such as effector T cells and microglial cells, by inhibiting kinase cascades and transcription factors. As an example, CBD dampens phosphorylated p38, which compromises AP-1 or NF-κB activity. Decreased NF-κB activity may also arise from induction of IκB. Induction of regulatory cells itself is a central way in which CBD controls immune responses. CBD has as well been shown to induce Tregs and MDSCs. Finally, CBD sometimes induces cell apoptosis. Popular discussion of CBD and the immune system, in other words, is hampered by reductionist understandings of what ‘the immune system’ is.
Scientific discussion is hampered too, by current limitations in knowledge. There is a lack of clarity, for example, in CBD dosing and plasma levels, and how these relate to immune modulation. There is one randomized, open-label interventional study planned, to assess CBD and THC on immune cell activation in HIV+ patients. This, and other studies like it, will illuminate the pharmacokinetic effects of dose-escalation relative to immune response.
Other research gaps exist as well.
A basic one is which receptor or receptors CBD acts on in the immune system. Does CBD-induced FAAH inhibition generate anandamide metabolites that bind to receptors that mediate some immune-suppressive or anti-inflammatory effects? It is known that some of the effects of CBD can be attenuated with PPAR-γ antagonists, so does anandamide production then drive production of other metabolites that activate PPAR-γ?
Another gap concerns which cell types the receptors are expressed on that mediate the CBD effects. Very little data exists, notably, for B cells and dendritic cells. Much is known in the CBD-T cell literature, but not on T cell subsets.
Finally, there is still a need for fundamental studies on the effects of CBD in immune responses that include consideration of variations in the method of administration.
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The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.
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