Ruffles said:
Loveall said:
I'm leaning towards forgoing handling freebase altogether and simply moving towards a salt soluble in PG (like DMT citrate).
Can you please elaborate on that?
Is salt-DMT vapeable??? If so, which salt would be better???
This has been in my mind since ever! Never had the guts to try it myself but just about to...
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To the point of this discussion... if the polymorphs exist as such, I wonder what would their pharmacokinetics would be.
Will digestion monomerize the polymorphs before absorption? Do we have specific enzymes for that (tryptophan polymorphs as storage)? Will oligomers have distinct absorption rates through all tissues? Do polymorphs or oligomers invade synapses? Do they interact with receptors? How would they modulate the effects?
Wonderful subject this one.
There is no monomerization, there is no difference in absorption because there is no difference in properties. Once DMT is in the solution phase, or virtually any other phase (gas, and liquid) the DMT molecules assume their regular free rotation and the molecules become absolutely indistinguishable. The purpose of my previous post was to highlight this fact by looking at DMT 1H NMR, and comparing it with a molecule that does exhibit different chemical environments in the solution phase, although I admit it was not really fully fleshed out. Polymorphism is very common among organic compounds, because organic molecules have a high degree of complexity, so a low degree of symmetry (lots of possible bond rotations and conformations, and ways to pack inside a solid crystal). Chocolate (cocoa butter) has something like 6 unique polymorphs, with specific ones being ideal (give you a chocolate that is solid at room temperature and has a good texture when you bite into it).
The point is, that has been missed, is that these interactions are only relevant in the solid phase or in the liquid-to-solid phase transition. It is only when the molecules are tightly packed, like in a solid or a liquid, and the temperature is low enough (to solidify), that the bond rotation becomes significantly hindered enough so that different chemical environments arise, and those differences express themselves with different chemical properties, like melting point, color, and in their spectrograph. Just like it doesn't make any sense to inquire about a chemical compound's density when it's in the gas phase, or a metals malleability and tensile strength while it's in a liquid phase, it doesn't make any sense to inquire about a polymorphs properties beyond the solid phase. You're not alone in this misinterpretation in this thread as well as other threads describing something similar, and referring to it as an "oligomerization" or "polymerization" (which, for added confusion, should really be referring to the formation of covalent bonds, not the non-covalent interactions being discussed here) which led to a lot of chasing ghosts and theorizing based on the incorrect interpretation of the phenomenon and misunderstanding of the diving forces at work. For the same reasons, it doesn't make sense to talk about pi-stacking interactions taking place in solution, to cause aggregation of molecules in the solution phase (especially aqueous solution) which is taking the interactions out of their actual context.
The crux of what we are discussing here, the phase properties of matter, and it is an extremely deep question in of itself, and not very intuitive at the most fundamental level. It should start with asking questions like "why are gasses compressible and why are liquids incompressible?" the phases of matter are not elementary properties of the individual atoms or molecules, but instead are emergent properties out of how matter is interacting with itself. The important thing to remember then, the environment dictates what forces will determine the behavior of the system. For example, the weak intermolecular forces that bind molecules together in a solid, are not at all relevant they are dissolved in solution. Or often we will talk about how powerful water hydrogen bonding is, so much that it can stay liquid up to 100C at 1atm, except above that temperature, even though it possesses this powerful property, water suddenly doesn't seem so special, because its hydrogen bonding is no longer relevant in the gas-phase.
You can even sort of think of it like a government, or the properties of people as a whole compared to their fundamental properties as individuals. The force of government will not dictate the properties of any one individual person, but it will supress some properties it doesn't wish to see, and encourage others, and that can change the properties/behavior of the system of a whole. When that regime changes, the behavior of the system changes, not because anything new has been injected into it, but what properties of the individuals that were already there underlying it, and it will change dramatically until it reaches a new equilibrium, which is an energy intensive process. This is like a phase-transition. Perhaps a better example, is when you transition from dreaming consciousness to waking consciousness, or after taking a good dose of a psychedelic. Your consciousness is undergoing a phase transition, because the boundary forces that are governing your current state of consciousness has changed, and different properties can emerge.
Another, even more primordial example, is even in the fundamental forces underlying the universe itself. We know of one clear example where the entire universe underwent a phase transition, during the rapid cooling and expansion the electroweak regime transitioned into the current regime, where before, you had a single electroweak force, to now you have the electromagnetic and weak nuclear forces. This completely blew my mind when I first conceptualized it in this way. And it points to, and leads you to wonder what forces and what phenomena are really truly fundamental. In the same way that if you have liquid water and rapidly reduce the pressure, the hydrogen bonding isn't enough to keep the water together as a liquid and it transitions into a gas where that hydrogen bonding 'force' no longer exists. The electroweak force no longer exists in our universe as a driving interaction (but it still exists!), but at one point it was as real as electromagnetism today, and these conditions can be recreated in a particle accelerator.
