Posted by Miguel (126.96.36.199) on July 26, 2000 at 07:59:19:
In Reply to: LSD blood-brain absorbtion posted by Q on July 26, 2000 at 01:59:30:
Thanx bud...right on the nose, as usual....
Now, here is a trickier endeavor...he he he....
Is that portion of LSD making its way into the brain
via active or pasive transport?
The point is that it might be that the amount
carried into the brain may not vary much
according to dose. Where the data you provided may
indicate that although a small amount of LSD
makes its way into the brain (one of the lucky
few agents that do so), and provided that its effects
are solely derived from its interaction with
brain physiology, the number of 5-ht2A receptors
in the brain must be rather limited. Additionally,
the generation of such receptors might be quite slow.
This would be in line with the possibility that the
mechanisms and pathways involved and activated through
5-HT2A subtype receptors might be secondary, non-essential,
possibly extremely specific. Further, because of
LSD's apparent partial agonist effect on 5-HT2A
receptors, this may explain its efficacy in the
temporary remission of CH (if indeed CH is mediated
through 5-HT2A receptors in an exclsive manner).
Think of LSD's partial agonist/antagonist paradox
as that of the 1/2 full / 1/2 empty glass perspective.
Also, data to corrobrate the following concept is
missing, but would be of importance to settle
the receptor spcificty and temporary nature of LSD's
dependant relief qualitites; Is the LSD - 5-HT2A
receptor interaction that of irreversible binding?
If so, and according to data that suggest that:
1) It crosses the blood-brain barrier
2) Partially blocks 5-HT by acting as a partial agonist
3) Small population of 5-HT2A receptors in the brain
4) Low rate of 5-HT2A receptor production
The beneficial effects observed from LSD 's interaction
with 5-HT2A receptors in CH would be then explained,
as well as its lasting effect in preventing the
ailment from recurring over several months.
The key to all this would be in data that specifically
addresses the Km of LSD in relation to
5-HT2A receptors. This could be easily done both
in vivo and in vitro. In vitro, it
would simply be a matter of using radio-labeled
LSD and 5-HT2A receptors to determine disociation
constants, and equilibrium states.
In vivo: I am curious as to what happen
to LSD molecules entering the brain after
a set period of time. Set up an experiment in which
patients are given sub-recreational doses of radio-labeled
LSD and take urine, sweat and feces samples for a period
of 1 year (the time noted by most for which LSD is able
to prevent CH from recurring) and look for radiolabeled
LSD or its metabolites (if metabolized).
another couple of questions that come to mind are:
1) How is LSD metabolized and cleared?
2) Since the liver seems to be the end point
of the majority of the dose, how long does it take
LSD to be excreted in the feces after the initial dose?
3) How is it excreted (chemical form)? As Glucoronide?
I am getting too deep in this without enough data to answer all the questions
that come to mind, which BTW seem to increase in number the more I look.
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