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Crosspost: Idea Regarding LSD's Method of Action

servalis

Bluelighter
Joined
Mar 17, 2007
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36
Preface:
I originally put this in BDD, but was told that I'd have better luck at finding a serious answer here.
This is pure speculation. I don't expect to make any significant breakthroughs in the understanding of LSD by this. I do though think that speculation of this nature has definite value in, at the very least, teaching me more about how the brain works. So please feel free to point out everything that makes this possible or impossible, I welcome everything. Thank you ahead of time.

I was reading about the Blood Brain Barrier in the book "Pharmacology for Chemists" by Joseph G. Cannon (great book btw) The book does such a good job of communicating its message that I'd rather quote it than paraphrase and pollute it.

Joseph G. Cannon said:
External Factors Affecting the Blood Brain Barrier
Animal experimental data and statistical studies in humans suggest that emotional and physical stress can increase the penetrability of the blood-brain-barrier to certain lipophobic organic molecules. Some drugs enhance blood-brain-barrier penetrability. For example, chronic use (or abuse) of amphetamines markedly enhances blood-brain-barrier penetration by other solutes in the blood, regardless of their molecular weight and lipophilicity. These permeability increases are said to be reversible in four hours, and they are associated with behavioral changes, increased locomotor activity, social withdrawal, and weight loss. Thus, some of the pharmacological effects effects that are described subsequently for amphetamines may not actually be caused by the amphetamine molecule itself. It may be admitting a variety of other molecules into the brain to exert the mischief.

Ok so LSD, as I have learned, does mimic Serotonin and acts as either an inhibitory or excitatory fashion though why it does one way on one receptor and the other on a different receptor is not known. However when they attached a radioisotope to LSD and tracked in the human body it spent only around 5 minutes in the brain and had completely evacuated to the gut by the time the effects were being felt.

My idea is that, possibly, LSD might be, in addition to setting off some neurochemical chain reactions, slightly altering the BBB temporarily and allowing for a variety of other chemicals to enter the brain. Grant it would likely be altering it differently from how chronic amphetamine use does as the effects described aren't exactly characteristic of the LSD experience.

I realize that this isn't a very likely scenario as the situation described involves chronic amphetamine abuse, and the BBB is a rather robust system. However I make exception here mainly because of LSD's rather mysterious qualities. I think that this, if true, may also account for the unreliability of the LSD experience to produce consistent results as the content of ones blood at the time of dosing may have more to do with the trip than previously believed. Thusly many other factors would come into play regarding the LSD experience such as diet, physical fitness etc.

My other idea in relation to this comes from the physical and emotional stress. LSD has, relative to other psychedelics, a massive trip time. Is it reasonable to suggest that the LSD experience might be self promoting in that, assuming my first idea to be at least partially correct, the physical and emotional stress of the LSD trip may further enhance or at least prolong the BBB's permeability?
 
However when they attached a radioisotope to LSD and tracked in the human body it spent only around 5 minutes in the brain and had completely evacuated to the gut by the time the effects were being felt.

Check your source. That's just not true.

That is interesting about the increased permeability, but I can confidently say that LSD does not act in this manner. I wonder what it is about chronic amphetamine use that alters the BBB? And it's odd that they say "chronic" but it resolves in 4 hours.
 
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Hmm I'm quite positive I read that in a pharmacology book, likely a dated one though.

The 4 hour thing raised my brow too.

How are you sure that LSD doesn't act in this manner, do you have a source or anything you can point me to?
 
As for the BBB, it's just common sense in pharmacology that the receptor interaction is what produces a drug's effects. Increased permeability might have some generalized effects, but I'm not sure how made any of the conclusions that it did, because there are many other factors that seem to affect behavior when you speak of stress and amphetamine abuse. For the rest, I'll refer you here for an answer:

http://www.bluelight.ru/vb/showthread.php?t=293450&highlight=LSD
 
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