[Immunology] Re: Endogenous and Exogenous Cannabinoids Modulate Inflammation

Kofi via immuno%40net.bio.net (by kofi from anon.un)
Mon Jun 18 01:03:10 EST 2007

> CB 2 agonists demonstrate remarkable anti inflammatory properties but 
> your
> idea of receptor attraction has some merit, at least with respect to the 
> CB
> 1 receptor. I recall an old study wherein they found that cannabis 
> tolerance
> was proportional to the level of receptor retraction from the cell 
> surface.

I wonder if, as with mu opioid tolerance, this effect is mediated by a 
PKC.  Would inhibiting that PKC result in elevation of cannabinoid 
receptor levels?

Also, B-cell proliferation appears to be partly under the regulation of 
a CB, although the research hasn't clarified it well yet.  I've always 
wondered if the way loss of gut bacteria knocks out the mu opioid and 
cannabinoid receptors of the gut wasn't also kicking antibody/B-cell 
production into needless overdrive (hence the use of B-cell depletion 
agents in autoimmune condition).

> This does raise some worrying questions with respect to the chronic
> ingestion of the same but the studies tend to find little ill effects.
> Cannabidol, the non-psychoactive form, strikes me as an excellent target 
> for
> therapeutic potential.
> A recent news release about some research indicated that topical 
> application
> of THC, which does ligand to the CB 2, had strong anti-allergic effects,
> sufficient to warrant clinical trials. This is entirely concordant with
> other studies showing that CB 2 activation down regulates excessive
> inflamation being driven by innate immune responses.

Well, I think it's a bit more complicated.  When you're deficient in 
vitamin D3 and/or butyrate, you've got a deficiency in production of 
antimicrobial compounds like cathelicidin and some defensins.  Examples 
of these chronic deficiencies range from tonsilitis to chronic rhinitis.  
Butyrate and D3 are also key factors which boost the function of 
regulatory T-cells, hence this deficiency would also increase 
allergies/asthma through underfunctioning Tregs.  What's even more 
interesting is that cathelicidin isn't simply an antimicrobial.  It 
seems to have antiallergic properties all its own.  So my thought about 
cannabinoids and allergies is that they may function by stimulating 
cathelicidin or some other innate defense component which also has dual 
antimicrobial/antiallergy actions.

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