Because of the Volume of Distribution of the cannabinoids and the
multicompartment models of how cannabinoids are distributed throughout
the body, THC and related compounds tend to accumulate in the brain
and liver. There is some accumulation in adipose tissue, but in
general, unless you are losing or gaining weight, there is not that
great of perfusion of blood in these areas compared to the brain and
liver. The situation is analogous to arterial plaque formation, but
since cholesterol does not behave quite the same way as the
cannabinoids at the blood brain barrier, and since the cannabinoids are
not actively made in the liver, and since all orally absorbed
cholesterol passes through the liver before going into the systemic
circulation, you do not find THC plaques on the arterial walls. So
this is probably related why there are not THC plaques everywhere. Also
remember that pot is smoked and if large amounts were taken orally over
long periods of time, there may be more similarity. Cholesterol is the
starting material for many hormones and in that sense, it is actively
transported to a much greater extent than cannabinoids. Expecting
cholesterol and cannabinoids to behave similarly in the systemic
circulation is not very realistic because there are so many differences
in so far as the way the two behave in the body from a purely chemical
perspective (forgetting about pharmacology for a minute.)
As far as the etiology of working memory loss, you cannot assume
causality just because there is resin in the brains of many heavy pot
users, and they have poorer working memories as a population. You
cannot make the leap and say that A is the cause of B. But they do
correlate with one another.
If I can find some of the imaging data around here I will try to email
it to you, but this is an opiates lab and it will be like finding a
needle in a haystack. I have a copy of Brain Research with a great
article on this issue and if I get some time I will try to find it and
send you a copy.
I knew this would open a can of worms whenever anyone blasphemes the
precious ganja, there is hell to pay.
MobiusDick
creamedbrainsontoast wrote:
> "MobiusDick" wrote:
>
>> I am speaking euphemistically. You get tar like deposits that remind me
>> of bong resin in the brain, liver and other fatty areas of the body. It
>> is not literally bong resin, it is fat soluble cannabinol derivatives
>> that precipitate out of the blood in these fatty areas due to the
>> thermodynamics of hydrophobic interactions (and London forces and all
>> those other physical chemistry terms that are beyond the scope of this
>> discussion --although if you want to get into the PChem of it, we can.
>
> is the mechanism akin to the deposition of fatty acids in the bloodstream
> as in coronary artery disease or the liver in steatosis? if you've got
> any pictures sitting around of some of these deposits, i'd be curious to
> look at them. it seems like one would have to smoke *a lot* (i'll be
> technical here -- a metric shittonne) of the pot in order to end up with
> any sort of significant deposits of cannabinoids forming anywhere. in any
> case, i'd expect them to disperse themselves pretty evenly throughout the
> adipose and brain tissue and whereever else lots of fat hangs out (i
> imagine a bunch of triacylglycerides leaning against a wall somewhere,
> waiting for passers-by so they can pop out their switchblades and mug
> them. what is wrong with me? must be all the dope i smoked in years
> past). but, i'm not especially versed in the thermodynamic properties of
> cannabinoids vis-a-vis the other lipophilic/hydrophobic compounds that
> stone cold chill in the body, jus' doing they thang.
>
> and thanks, but no thanks, for the pchem lecture.
>
>> These deposits in the brain disrupt neuronal transmission and probably
>> have something to do with why working memory (once known as short term
>> memory) is so grossly affected in heavy users after a long period of
>> time.
>
> again, i'd be curious to see these deposits for myself, and to know how
> much of the grass these cats were blowing, or if they did other shit that
> might have caused neurological deficits. i do know that if you wait long
> enough, even without doing any (recreational) drugs, your memory starts
> to hit the fritz anyways. my intuition is that people that smoke the
> reefers, over a period of years to decades, and get used to living in a
> stoned haze, when they finally stop and wait a couple of months for the
> accumulated cannibinoids to get completely flushed out of their body and
> discover that their memory isn't as sharp as it was before they started
> smoking the doobie to begin with, they're liable to blame the ganja for
> the loss of their short-term memory, when in fact they're no more
> forgetful than anyone else their age, give or take.
>
> i've seen a similar phenomenon happen with people who do varying amounts
> of drugs for varying amounts of time and then once they decide to go
> straight they feel like their cognition isn't as sharp as it used to be,
> or their memory isn't as keen, or what have you. but it's impossible to
> say for sure that it is in fact the result of neurological damage wrought
> by "drug abuse" and not one of a myriad of other things that could have
> come in to play, the simplest of which is that they just over-estimate
> their pre-drug cognitive abilities and fail to compensate for the passage
> of time. another thing is if one goes from keeping their mind busy with
> something that is mentally demanding and then spend a while eating
> cheetos and playing grand theft auto while doing bong rips every 20
> minutes, their cognitive abilities are going to decline (except for the
> ability to shoot a bunch of cops and grab the tank and go find a corner
> of the map where they can blow shit up unmolested for hours at a time)
> simply from disuse. it's like suddenly stopping a rigorous exercise
> regime and laying in bed for a few months and wondering why when you try
> to get out of bed finally your muscles have atrophied.
>
> i worry that automatically assuming that any sort of cognitive decline,
> real or imagined, that appears (or seems to appear) over the course of
> one's drug-using career, and (seems to) continue(s) after going straight
> simply makes it more difficult for people to move on with their lives.
> it's very possible to feel sluggish and retarded without being either,
> but believing that you feel sluggish and retarded and can't think as well
> as you used to because of drugs and they've crippled you for life is a
> pretty well self-fulfilling prophecy.
>
>
>
>> But the general point is that heavy pot use is far from harmless. Oral
>> opiates, without acetaminophen or ibuprofen, have a much milder long
>> term effect on the body and brain over time that pot does (not to say
>> that opiates cannot ruin your life easier than pot can, but
>> physiologically there is not any real irreversible damage done.
>
> and "MobiusDick" later spake:
>
>> But as far as marijuana being harmless, that depends on what you mean
>> by harmless. Does it cause pathophysiological changes with heavy use?
>> Putatively yes. Is it as addictive as heroin and does it cause people
>> to go into severe withdrawal. No. THC withdrawal is minor due to its
>> long duration of action (unless precipitated by a CB antagonist, where
>> it is fairly severe.)
>
> do you know of any journal articles about dosing potheads with cb
> antagonists to see what happens? have they done human trials with them
> yet? i've read about what happens when you do it to mice. as far as long-
> term problems from the doob, they seem to be less severe than you'd
> think, especially with regards to the respiratory tract. it's pretty
> well-established (imo) that smoking cannabis alone doesn't increase the
> risk of lung cancer or copd significantly over baseline, and may well
> have a protective effect. compare that to the effects of tobacco use on
> lung function. as for the rest of the body, i haven't seen as much
> research, but i have the feeling that, except for the hardest of the
> hardcore potheads out there, any negative sequelae to their dope-smokin'
> ways are pretty minor. certainly less than those associated with alcohol
> or tobacco, or high-dose, long-term methamphetamine use.
>
> but this is a hard drugs group, and it's time to stfu about pot. like you
> say, opioids are about as safe a class of drugs as there exist today. the
> withdrawal syndrome is a bitch, and their illegality makes balancing a
> habit with the rest of one's life much, much, much more difficult than it
> otherwise would be, or should be, but neither of those is so much a
> result of the substances themselves as it is of their political
> situation. [w/r/t w/ds, i mean that given effectively unlimited access to
> opioids, no one would have to go through withdrawal unless they wanted
> to, unlike today where supply is so tightly restricted]. except for --
> what -- constipation? miosis? -- someone can be physically dependent on
> opioids for their entire life and not suffer any ill effects from the
> habit. i don't know any other class of drugs that are so remarkably
> without toxic effects when used over extended periods of time.
>
> now, if only we could start treating addiction as a sociopolitical
> problem instead of a biological one or a criminal one....
>
> --
> -creamedbrainsontoast
> "One tablespoon of butter, one egg yolk, one scant tablespoon of flour,
> salt and pepper to season, half cup of milk, three-fourths pound of
> brains. Parboil the brains. When cool, salt to taste and chop in small
> pieces. Cook flour and butter in double boiler; add milk and beaten egg
> yolk and stir slowly into butter and flour, add seasoning and brains.
> Cook about three minutes and serve on toast."
