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Brain Slices, THC and PGE2.

BilZ0r BilZ0r at TAKETHISOUThotmail.com
Tue Jan 6 00:34:49 EST 2004

I agree with the majority of things you say there.. although, I wasn't 
awear of any good human histological cannabinoid studies. The majority of 
murine studies see altered histology in cannabinoid treated aniamls, and 
half of the primate ones see it.

I'd really like to see if using a COX inhibitor on THC treated animals 
would have any effect on spatial memory impairments caused by THC.

and ps, have you ever seen how Tommy Chong acts in reality... I see a 
preety clear sign of something being wrong with his brain... lol.

"John H." <johnh at faraway.> wrote in news:3ff9cbba at dnews.tpgi.com.au:

> Another damning question in neuroscience. In vitro studies tend to
> support a neurotoxic potential for cannabinoids but in vivo the
> picture is very different. If the neurotoxicity purported from the in
> vitro studies were real and substantial, and given the Cheech and
> Chong habits of some potheads, then long term heavy M users should
> have brains like dried cabbages. However, contined exposure quickly
> internalises CB 1 and 2 receptors, hence the relatively high tolerance
> that can quickly develop upon chronic exposure. Various longitudinal
> studies demonstrate limited if any cognitive impairment (though
> immunological impairment is noted - however questionable is this
> actually results in reduced immunological efficacy) and imaging
> studies on humans do not demonstrate tissue pathology. 
> One report last year claimed that a major problem with in vitro
> studies is that the cultures are typically exposed to much higher
> oxygen concentrations than occurs physiologically.
> The culture medium could be an important factor.
> Another matter to consider is that cannabinoids are highly lipid
> soluble, so what is deemed to be a physiologically relevant level of
> exposure may be incorrect because in the body most cannabinoids could
> be absorbed by lipid tissues rather than activating CB 1 and or 2
> receptors. This level of lipid solubility is such that some have
> suggested, and I think this has been experimentally demonstrated, that
> cannabinoids directly impact on second messengers independently of CB
> 1 or 2 occupation. In this regard I recall one study which stated that
> CB occupation can be relatively low to generate a psychoactive effect,
> circa 8-10% of total receptors. So it may be interesting to measure CB
> occupation in the culture and slice studies. Another approach may be
> to look at PLA 2 and PKC activation under these conditions, I suspect
> it may be much higher than occurs physiologically. As PGE 2 increases
> vasodilation excess oxygen exposure may become an issue. I'd be
> interested to see what levels of PAF occur under the experimental 
> conditions re slice and brain studies as PAF is usually neurotoxic. 
> Another approach may be to look at other compounds and their effects
> relative to the various experimental paradigms.
> Another issue to consider is that cannabinoids inhibit NMDA activity,
> so their protective effect in the body may be mediated via this and
> other factors such as cannabinoids possessing considerable
> anti-oxidant capacities which may be negated by the relatively high
> oxygen concentrations in slice and culture preparations.
> Also cannabinoids generally have a marked anti-inflammatory response,
> strongly limiting tnf and il1 from mononuclear cells, though at higher
> concentrations the reverse may occur.
> I think this is an important issue that could help elucidate the
> issues surrounding slice and culture studies. I haven't had a chance
> to look closely at this matter but am  interested in what others have
> to say. 
> John H.

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