[Neuroscience] Re: Chemical access [Was: Re: Appropriate newsgroup?]

r norman NotMyRealEmail at _comcast.net
Mon Nov 28 14:40:16 EST 2005

On Thu, 24 Nov 2005 17:14:18 +0100, Jure Sah <jure.sah at guest.arnes.si>

>r norman wrote:
>> This would be a good choice.   Ask away!
>> There are a variety of neurobiologists who reside here.  I am more of
>> a physiologist, but I am familiar with a reasonable portion of
>> neurochemistry.  There are others here more  expert on just that
>> subject.
>Thanks! Well here it goes:
>I've long heard rumors that various drugs cause damage to the membrane 
>between the blood and the brain ( 
>http://en.wikipedia.org/wiki/Blood-brain_barrier ).
>The idea was that the drug has to pass trough this membrane to get to 
>the brain, which isn't normally possible (or is normaly obstructed) so 
>in term causing damage to it, increasing the sensitivity of the brain to 
>other chemicals and infectious diseases (as well as a possible hormone 
>feedback-loop effect, but that possibly wouldn't be quite as observable).
>Now I've had some (illegal) drug takers confirm that that must be the 
>case since when they first took a drug, a larger dosage was required to 
>reach the same effect than after 2 to 4 times later. And while I do 
>think they are convinced this is true, that is not to say it actually IS 
>true. I'll need a bigger sample size.
>I searched the web and only came accross one article describing how it 
>COULD be that ecstasy has such an effect (but then again, Google and 
>medical archives have never been very good buddys). And now I do not 
>know wether the rumors I have heard are based entirely on one or two 
>articles like this, or is such an effect, tho perhaps not fully 
>scientifically confirmed yet, observable with most drugs.
>Also I have no information about how fast is this membrane capable of 
>regenerating after suffering possible damage from drugs (now there must 
>be SOME drug that does damage it specifcally, just to find this out)... 
>Is it weeks? Months? Years? Decades? Does it even occur?
>I'm not really muchly into this sort of science (I'm a software 
>devoloper by profession), therefore amateur in my knowledge about it 
>this far. I'm just really curious.
>Looking forward to any answers.

I tell you that this is the right place and then abandon you. I am
sorry.  But Thanksgiving weekend was filled with relatives including
an incredibly adorable first grandson who seemed to occupy far too
much of my waking hours.

You are correct that there is a blood-brain barrier that blocks most
drugs from moving from the blood stream into the extracellular
environment of the brain and so be able to influence brain function.
And anything that influences the integrity of this barrier could allow
all sorts of very nasty effects.  However changes in this barrier are
not generally associated with phenomena like drug tolerance, the
phenomenon you describe.  And, yes, tolerance to MDMA (ecstasy) is
very real.

Drug tolerance can have many different causes.  First, there are
"detoxifying" mechanisms at work both in the body (the liver, mainly)
and in the brain to eliminate "foreign" substances from the body.  And
there are also processes to terminate the effect of naturally
occurring signaling substance (neurotransmitters and hormones) by
inactivating the chemical or transporting it to a location
(intracellular) where it produces no effect.  Sometimes, the presence
of that chemical acts to stimulate production of the enzymes that
degrade it or the transport systems that eliminate it  In either case,
subsequent doses are eliminated faster than earlier ones so larger
concentrations are needed to produce the same effect.  Then there are
psychological factors.  The first dose of ecstasy is supposed  to
produce (so I read, I have never tried it) a very novel "high" that
promotes the desire to repeat the experience (even though the drug is
not supposed to be physiologically addictive in the technical sense).
The effect of later doses is already anticipated to some extent so the
effect is different.  Also, psychological habituation or attenuation
of the response due to complex but purely neural mechanisms could well
be involved.  That is, the drug may still produce the same physical
response in those neurons that act as ecstasy receptors but plastic
changes in the nervous system result so that later stages of neural
processing are weaker.  Then there are molecular biological factors:
the presence of a drug or signaling agent may "downregulate" (that is,
reduce the activity of) the genes that produce the receptors that
respond to the chemical so that again subsequent doses produce a
smaller effect.

I don't know exactly what the mechanism is for MDMA (ecstasy).  The
best site I could find is AC Parrot's study found at

You are right about google searches -- you get a lot of non-technical
stuff that may be good or may be trash.  Try using advanced google to
search "MDMA tolerance" only in "edu" sites  Or search the technical
literature using Entrez/Pub Med at
Again, the Parrot study seems to be the best one in this area.

Knowing the details of the mechanism for ecstasy (MDMA) tolerance is,
frankly, not of that much medical importance.  The fact is that it
does show marked tolerance so that chronic users take very large
quantities.  And the fact is that there are major very bad
consequences of chronic MDMA usage, not to mention the very common
hazards of using impure or counterfeit drugs with quite toxic
contaminants.  Search "MDMA toxicity" for more details.

Do the toxic side effects "wear off" and, if so, how long does it
take?  That is a problem you will have to explore searching
Entrez/PubMed (again, for "MDMA toxicity") because a lot depends on
just what the mechanism of damage is.  If it is up- or down-regulating
the genes involved with serotonin, then the effects could possibly be
erased.  The time course could vary from days to weeks and months or
more.  If the damage is to the fine terminals of neurons as some
studies suggest, then it might well be permanent or it could reverse
with a time course probably measured in months and years.

Frankly, there are far better and safer illegal psychoactive drugs
that you should use if you insist of messing yourself up that
seriously.  And there are quite legal ways of deriving enormous
pleasure and satisfaction from life that have absolutely none of the
damaging side effects.  But it's your life (or that of your friends).

More information about the Neur-sci mailing list