johnYYYcoe at tpg.com.au
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"BilZ0r" <BilZ0r at TAKETHISOUThotmail.com> wrote in message
news:Xns93D8E9483969BBilZ0rhotmailcom at 22.214.171.124...
> Well its all a very interesting area of research. Although im not
> particularly awear of the articles you refer to. I imagine
> nonpsychoactive cannabinoids protect from ischemic damage via their
> antioxiditive properties, so vitamine E could be just as good.
IN the hampson study the non-psychoactive and psychoactive forms were better
than vitamin E and compared very favourably with the laboratory antioxidant,
BHT, equiv or better I believe.
> What I meant by the MK-801 comment was not just limited to the
> psychoactive side effects, but the fact that they have to be administered
> very soon after the stroke, so their usefulness is very limited.
Causes severe side effects. Cannabinoids have the advantage of limiting PQ
Ca channels without NMDA blockade. ie, maintain NMDA but keep Ca under
control. No idea why. Impact on both immediate and delayed (apoptotic) cell
death; latter probably via downregulation of il 1 etc.
> Don't get me wrong, the the in vitro studies arn't directly comparable to
> recreational/clinical usages of cannabinoids, but they do point out a
> need for caution. Also, you say that no neurtoxicity has been shown in
> vivo with sensible doses. It depends on how you define sesnible doses, if
> we account for the usual interspecies dosing changes, the doses given to
> mice to produce "neurotoxicity" are not that outlandish.
The preponderance of evidence clearly points to strong neuroprotective
effects in vitro.
> ...and of course, when I say neurotoxicity I mean the ICON definition, so
> that include morphological changes, which CB1 agonists of varying kinds
>>> As far as the Maccarrone et al article, its a rather interesting set or
> research. Some peopl then ending up concluding that neither receptors had
> anything to do with anadamide induced apoptosis, and it was a lipid raft
> mediated phenomena. In reality, I suspect its a complex interplay. But of
> course, THC dosn't activate the vanilloid receptor, so that whole
> argumennt is rather peripheral to THC-mediated neurtoxicity.
Important to remember anti-inflammatory component of cannabinoids, note that
CB 1 receptor common in brain but in immune system mostly CB 2. This is one
reason why in vitro studies are misleading. Neurons don't die just because
of intracellular processes, v. important to consider il 1, tnf a, il6, il12,
and microglial alteration in function.
> and as far as cannabinoids recieving more attention, well if I can charm
> my head of my department, THC/anandamide-mediated neurotoxicity is
> hopefully what I'll do my masters on.
I'm currently, vainly it seems, trying to understand transient psychosis
induction by cannabinoids. Some progress. To be honest, I think you should
focus your attention of cannabinoid - dopamine interactions. Note: have seen
quite a few refs to altered cannabinoid function in schizophrenia (high
levels of CB 1 in prefrontal cortex mainly). Chronic upregulation of
extracellular dopamine in striatum may be one means of neurotoxicity but the
antioxidant functions (v. good at stopping H2O2 I think) may counter this.
Don't know, too difficult, everything in this game is too bloody difficult.