Dose - pKa, pH, and LSD

[Shampoo]

A recent musing on the absorption principles of all chemicals, but in a direct and applicable sense, LSD: A key intention in ingestion is avoidance of ionization. If a chemical finds itself ionized, it becomes water soluble, and thus poorly absorbed by stomach, and in the case of application to pregnancy, placenta. If the chemical is de-ionized, it becomes lipid-soluble, thus the absorption rate rises (cell membranes are friendly with lipids...). The rate of ionization can be determined by a ratio of pKa to pH. These two numbers fluctuate according to the pKa of the chemical, and the absorption method. Absorption through an IV results in a pH according to blood, which is reliably 7.4. The pH of the stomach however is drastically lower, usually at 2.5.
So in application, the equation for absorption determined by pKa looks something like this 100/(1+10^x(pH-pKa)) where x is -1 is the drug is an acid, and 1 if the drug is a base.
When applied to LSD, the results are surprising based on readings of empirical testing of LSD administration. The intravenous administration of LSD inherits a 28.5% ionization rate, implying that that approximately 28.5ug per 100ug dosed intravenously is lost. Though not to many swimmers out there dose LSD with a needle, the sublingual digestion (i.e. blotter in the mouth...) implies intravenous digestion as well. The stomach however, with a pH of 2.5, has an ionization rate of 0%. Thus, 100% of the chemical is absorbed in the digestion process. This would imply that the use of sugar cubes and liquid suspension capsules far outperform in efficiency the use of the more common, perhaps more romantic or even more practical administration through blotter paper.

note: This does not account however for LSD lost during long arduous journey of oral digestion. If that is quantifiable, or has been quantified, please post in response.
Also, this has not been put into practice, as far as I am concerned, and should not be used as a reliable source of dosing calculations. (i.e. this does not mean that SWIY needS an extra 28.5%ug for accurate dosing...)(although it does allude to it)
On that note, microgram calculations are consistently unreliable, especially from SWIY. So unless a microgram scale adorns SWIYr laboratory, weight as a measure of LSD quantity may be less than accurate.

Reputation Comments on this post:

good post.

[Shampoo]

Final note: This does however imply some validity to the conceptual ingestion by the in-vitro fetus dependent on the mode of ingestion. As was determined, intravenous, or sublingual digestion of LSD involves a mixing with the blood. With the pH of blood at 7.4, and the pKa of LSD at 7.8, 28.5% remains undigested, and therefore will find its way to the placenta. Wether or not an in-vitro fetus has a developed enough set of 5-HT receptors is another question altogether, but this does prove that ingestion of LSD in a traditional blotter format, or intravenously, will result in placental absorption of the alkaloid.

[Cakes]

howdy Friend!

The text is saying that mothers send undigested food to the fetus? like little sandwiches? all food i eat must pass through the wall of the intestine to reach ANYwhere. and that is the definition of digesting something<when it passes from the bowels to the system.

water is poorly absorbed by stomach

We have to be careful when interpreting texts sometimes. just because something is "poorly" absorbed does not mean it goes unabsorbed. it often is a comparative term. as in the speed by which something gets absorbed or how long the body may hold it. yes a substance may be lipid friendly but lipids are fat. and so substances suspended in it may stick around well to cells but fat does not necessarily release it's contents in the same way that water does. you have heard of flashbacks? and (for some of us) it is caused by stored LSD. stuff that was "well absorbed". fat that eventually got burned.

I believe that water gets all the way absorbed as it goes through the body<that is why it can come out a different hole than it went in. i.e. it does not come out the small bowels, it comes out the urinary tract.

[Shampoo]

The text does not imply that everything that remains unmetabolized reaches the fetus, but rather that unmetabolized chemicals in the bloodstream frequently reach the fetal dwelling. As the mother and fetus do not literally share a stomach in the sense in which they share a bloodstream, the impact of 'tiny sandwhiches' is indirect and usually well-mediated, while the impact of foreign chemicals in the bloodstream usually has already defied the natural defenses of the body and will more likely be shared with the prenatal fetus. In the case of LSD, uterine contractions are more worrisome than a 'tripping fetus', but in many cases, this calculation can help determine what percent goes unmetabolized through placental tissue.

Lipid friendly substances generally reduce the impact of first-pass metabolism. Water does indeed eventually become entirely absorbed, but where, when, and how are what impacts the pharmacokinetics, distribution and metabolism.

Originally Posted by Cakes

you have heard of flashbacks? and (for some of us) it is caused by stored LSD. stuff that was "well absorbed". fat that eventually got burned.

While that is an intriguing, and reasonably logical explanation for the induction of flashback states, there are a few obvious problems. This is a question I have asked nearly every professor of psychology, neurophysiology, and pharmacology that I have had who I thought had a clue (and as a neuroscience student, there were quite a few...) and each one has agreed that outside of a couple month window, the pharmacokinetic explanation for flashbacks can be pretty unequivocally ruled out. The concept that someone stores LSD in non-specific lipid binding positions (or 'depot-binding' positions) may have some validity within hours, days, or even a few months of first metabolism, but the concept of lipid turnover requiring more than a few months sounds a lot more like a camel than a primate or human being. The above concluded that little to no LSD is ionized during oral digestion, meaning it has little resistance against crossing endogenous membranes and undergoes normal biotransformation. How could a reasonable 'second' dose (at least 20 micrograms, and in the case of many described flashbacks, an equal amount as the initial experience) remain unmetabolized and bound to these non-specific lipid binding sites? Additionally, wouldn't 're-digested' LSD that had been previously "well absorbed" act without any alteration? simply as the same LSD-25 that was initially ingested, implying that rather than an immediate 'flashback' moment, there would be a complete rebiotransformation, starting with an hour or so of come up time, followed by a reasonably multi-hour long peak and an afterglow? Why would 'redigested' LSD act any differently than before it had been 'stored'? More poignantly, lipid turnover is not a lifelong process for humans, assuming they eat, breathe, and move on a regular basis. A dormant bulimic might have a chance of retaining the depot-bound lipid-LSD compound, but any human with an active metabolism and a healthy pharmacokinetic system will be rid of any depot-bound LSD within a few months. While there are many theories explaining LSD flashbacks, from the ludicrous (LSD is stored in your spine and re-released when you crack your back) to the rational (state-dependent learning/trauma), the concept of lifelong lipid storage seems pretty reasonable disproved by basic pharmacokinetics. If this is not true, and all of my professors have been talking through their teeth, please let me know with some contrary medical evidence.