Cranial blood flow

[perpetualdawn]

Sekio put up a link to this informative poster on the PD forum:
http://tripzine.com/pit/signal_theory_poster.pdf

I have a question about one section from the poster. It says:

When trying to understand how psychedelics act as "non-specific amplifyers[sic]" of the psyche, it can be assumed that recurrent excitation caused by hallucinogens follows the path of the bloodflow through the cranium. As an analytical circuit becomes excited and demands more blood, more drug is borne to that circuit via the bloodstream, further exciting the targeted circuit.

How valid is this? Is it true that as a brain circuit gets excited that it demands more blood? I always assumed that blood supply remains more or less constant to all parts of the brain.

 

[sekio]

It's a principle of fMRI, so yeah, it happens.

 

[perpetualdawn]

That's amazing.

It seems to me that the drugs that have partial affinity to the receptors should display this effect more than the ones with high affinity. High affinity drugs should end up getting locked up on the receptor sites, so they won't move around as quickly in the bloodstream to new sites where the bloodflow is being directed. On the other hand, lower affinity drugs should be bumping around more, falling off the receptor sites and then re-circulating more readily and ending up in newly blood-rich circuits.

Does that seem like a reasonable theory?

 

[endotropic]

That's amazing.

It seems to me that the drugs that have partial affinity to the receptors should display this effect more than the ones with high affinity. High affinity drugs should end up getting locked up on the receptor sites, so they won't move around as quickly in the bloodstream to new sites where the bloodflow is being directed. On the other hand, lower affinity drugs should be bumping around more, falling off the receptor sites and then re-circulating more readily and ending up in newly blood-rich circuits.

Does that seem like a reasonable theory?

I can see why you would think that, but drug/receptor affinity probably doesn't have much of an effect on circulation. There are millions or even billions of drug molecules present for every receptor, so the one drug molecule that sticks is really just a drop in the bucket compared to the amount still floating around.

 

[perpetualdawn]

OK good to know!

It would be interesting to make a guess at just how many 5ht2a (for example) receptors there are in a typical human brain. Any idea?

 

[perpetualdawn]

I'm going to take a very crude stab at guessing an anwer to my own question:

Say 100 billion neurons in the nervous system. 10^11
Say there is an upper limit of around 100,000 dendrites per neuron 10^5
Say there are 1 million receptor sites per dendrite (this is a complete wild guess) 10^6

So my guess is 10^22 receptor sites in the human nervous system. Of those, say max 10% are 5ht2a. So 10^21 receptor sites.

There are 1.5x10^17 molecules of LSD in 100ug. (http://www.erowid.org/ask/ask.php?ID=3083). So there might be something like 10^5 molecules of LSD floating around per 5ht2a receptor site, when you dose 100ug.

This is all a very wild guess tho and is probably out by many orders of magnitude.

 

[endotropic]

I'm going to take a very crude stab at guessing an anwer to my own question:

Say 100 billion neurons in the nervous system. 10^11
Say there is an upper limit of around 100,000 dendrites per neuron 10^5
Say there are 1 million receptor sites per dendrite (this is a complete wild guess) 10^6

So my guess is 10^22 receptor sites in the human nervous system. Of those, say max 10% are 5ht2a. So 10^21 receptor sites.

There are 1.5x10^17 molecules of LSD in 100ug. (http://www.erowid.org/ask/ask.php?ID=3083). So there might be something like 10^5 molecules of LSD floating around per 5ht2a receptor site, when you dose 100ug.

This is all a very wild guess tho and is probably out by many orders of magnitude.

This information is out there, but might not be particularly easy to find. When receptors are quantified biochemically they're reported as fmol of receptor / mg of total brain tissue. So if you can find can find a value for 5-HT2A reported in fmol/mg you can multiply by the total weight of the brain to get a good idea for total receptor number.

Alternatively you can look at PET studies that use a 5-HT2A radioligand. I know they can quantify receptor expression in those studies, but I don't know exactly how.