[Immunology] Endogenous and Exogenous Cannabinoids Modulate Inflammation

John H. via immuno%40net.bio.net (by bingblat from goaway.com.au)
Fri Jun 8 04:25:35 EST 2007



Of course they do, the literature on this is enormous and compelling. A
seminal article is Hampson et al, PNAS, July 1998, wherein they found that
THC and the non-psychoactive cannabinoid, cannabidol, had antioxidant
properties better than vitamins C or E (vitamn E might be a furphy because
it may not be an antioxidant) and comparable to the best laboratory
antioxidant they had available, BHT. An article I recently read found that
THC markedly decrease CD40 expression in microglia, a critical component in
the inflammatory pathway. This one article alone goes a long way to
explaining what Hampson et al refer to as the potent neuroprotective
qualities of cannabinoids. Interestingly, only last night I learned that CB2
expression is prevalent on astrocytes, obviously present on microglia but
astrocytes??? Very significant because CB 2 activation, generally found in
immunological cells, plays an important role in modulating inflammation.
Nature magazine published research only two months ago demonstrating that
low dose THC iv infusion into genetically engineered mice prone to
atherosclerosis had a marked effect in reducing atherosclerosis; this
finding being entirely concordant with its known impact in reducing immune
mediated inflammation and the now prevailing view the key initial trigger in
atherosclerosis is the oxidation of LDL and possibly of more importance the
oxidation of vLDL. Recent findings have also established that within the
plaques resides necrotic macrophages, necrotic cell death being a strong
inducer of an inflammatory response via Toll receptor activation. But
there's more, in Mole Pharm Oct 6, 2006 there is an article demonstrating
that THC and cannabidol strongly inhibited acetylcholinesterase by attaching
to the anion site thereby not only inhibiting its action but also preventing
amyloid expression because it is this portion of that enzyme that seems
direclty implicated in the production of amyloid. The authors of that study
concluded that these exogenous cannabinoids demonstrated greater efficacy
than all the current drugs available for Alzheimer's Disease. Of particular
significance is that current pharmaceutical strategies in relation to
alzheimers is to increase acetylcholine production (the above enzyme
degrades it) and reduce amyloid production. And there's more, research
published 12 months ago found that synthetic cannabinoid, HU210, with an
affinity to the CB 1 receptor being 100 times that of THC, markedly
increased neurogensis. This incidentally, fits in well with some ideas I
have been exploring in relation to hippocampal atrophy via reduced GABA
transmission (note: THC is a retrograde inhibitory neurtransmitter
particularly active under dopamine stimulus hence had an inhibitory quality
like GABA) leading to loss of BDNF, as does increased il-1 expression, also
inhibited by THC and cannabidol. Complex, lot of work to do there. Now if
you really want to get spooky, there is the CMJ article claiming that light
pot smoking actually increased iq by 5.8 points. This would not be true of
people under 25, but given the emerging view of age related cognitive
decline one can make a strong argument to the effect that very moderate use
of pot may help protect the brain from age related decline precisely because
with age microglial activation tends to increase and there is some evidence
to suggest iron levels increase; the latter being problematic because free
iron (Fe2+,3+) can, via haber-weiss and Fenton reaction, induce oxidative
stress with peroxynitrate (ONOO) being a real problem in this context.


Then there's the fact that cananbinoids have demonstrated remarkable
anti-tumoral properties, particularly in relation to gliomas. This
potentially relates to the CB 2 receptor again but there is a fascinating
relationship between ceramide production induced by cannabinoids, oxidation
status, the tendency for cells to slip into apoptosis. This is the big
problem with cancer cells, often their mitochondria are not working well,
and as mitochondria play a fundamental role in cell death pathways cancer
cells can be highly resistant to programmed cell death. Probably will never
understand this and I remain doubtful cannabinoids will be that useful in
cancer treatment but with the important exception of gliomas. Inhibition of
CD40 and IFN gamma clearly suppress microglial function and it may be the
case that gliomas are precipitated by cells slipping out of the G O phase.
I'll stop there this could go on and on I really must stop smoking pot.




http://www.sciencedaily.com/releases/2007/06/070607171120.htm

Constituents Of Hashish And Marijuana May Help To Fight Inflammation And
Allergies

- Endocannabinoids seem to play an important role in regulating inflammation
processes. Scientists from the University of Bonn have discovered this in
experiments on mice. Their results will be published in the journal
'Science' on 8 June. The study may also have implications for therapy. In
animal experiments, a solution with an important component made from
cannabis reduced allergic reactions of the skin.


Extracts of the hemp plant cannabis are traditionally used as a popular
remedy against inflammation. At the beginning of the last century this
natural remedy was even available at every chemist's. But due to the
intoxicating effect of the component THC (tetrahydrocannabinol) the plant
was taken off the chemist's shelves in the 1930s.







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