I was simply pointing out that the dose needed to get that concentration is ridiculously high and would never be achieved by normal recreational doses.
This is the same reason that all of the studies showing neurotoxicity in rodents and non-human primates for MDMA are inherently flawed. It was either IP injection or direct injection into the brain, sometimes of extremely high doses even when taking cross species allometric scaling into account.
Ah, yes, this I agree with. Sorry if it wasn't clear on my original post, english is not my native language.
The point that I'm making is you can make a reasonable assumption that the maximum concentration in the brain is going to be the dose divided by volume of water in the body.
My only issue was with this assumption, the drug is not going to be dissolved in the total water volume of the body. For starters, intracellular space makes up roughly 2/3 of the total water volume of the human body, and the drug won't get inside most cells. At peak concentration, drugs will be mostly carried by plasma. They will eventually, of course, slowly diffuse into some other tissues, and to the different excretory organs which apparently include cebatious glands
which is part of the reason why some drugs end up in our hair. But they wont get literally
everywhere in the body, and by the point they are the most dispersed in it, the different metabolizing enzymes have already acted upon them. So I guess what I'm trying to say is that (Dose consumed/Total water volume) is not a very good approximation of the highest concentration you will found in the brain after ingesting a given drug, because drug elimination starts as soon as it enters the bloodstream. This is the reason peak
plasma concentration is usally used as a measure of a drug's bioavailability. The
distribution of any given drug from the plasma to the different tissues is determined by complex factors and will vary from molecule to molecule, with some staying mostly in plasma and other venturing elsewhere, though never homogeniously throughout the body. Some drugs tend to accumulate in adipose tissue, others predominantly remain in the extracellular fluid, and some bind significantly to specific tissues.
But you are anyways completely correct about the fact that the cited
In vitro study is using molar concentrations grossly above normal recreational doses. The bloodstream concentration of a drug upon ingestion is determined by several factors, including the rate and extent of absorption of the drug from the site of administration into the bloodstream, the extent to which the drug is distributed throughout the body after entering the bloodstream, the rate at which the drug is metabolized or broken down inside the body, etc...
Hope I made myself clearer this time !
Aside from substances that don't pass the blood brain barrier, can you tell me something that doesn't actually get next to every cell in your body?
Yes, individual cells do prevent certain substances from crossing the cell membrane, but we're talking about exposure to receptors.
I mean it's pretty clear that methamphetamine and MDMA and cocaine all end up in hair. Follicle hair shaft toenails fingernails all over the body. It's excreted in sweat so please explain how it doesn't get into every cell. I guess the bones don't count.
Well, most molecules we ingest won't get inside
every cell type, otherwise everything would be incredibly toxic. Cell membranes are semi-permeable, but for the most part there is a complex regulation of what goes in and out of cells. Molecules don't go freely across cell membranes, even for ubiquitious stuff like glucose there are
specialized transporters. Hell, even
water entry into the cell is regulated. For molecules that mimic monamines in the body, like phenethylamines, the same regulation exists. Most molecules won't enter or interact with a cell if the latter doesn't have the specific receptors that allow the interaction. Drugs are designed to interact with specific targets in the body, such as cell-receptors, enzymes, or other proteins. Not all cells in the body have the same set of targets. Overall, the ability of drugs to enter and interact with different cell types depends on an interplay of factors, including the properties of the drug, the characteristics of the cell, and the specific target that the drug is designed to interact with. While some drugs may be able to interact with and enter into a wide range of cell types, others are more limited in their ability to do so.
