The Small & Handy Polymorphism Discussion Thread

[.:Holy::Toast:.]

Once the drug has been absorbed in to your blood stream, and further your BBB, there should not be any specific morphism, it is dissolved in your blood so all batches SHOULD react with your receptors identically.
I see no reason for polymorphism to be relevant when discussing effects.

 

[Help?!?!]

Once the drug has been absorbed in to your blood stream, and further your BBB, there should not be any specific morphism, it is dissolved in your blood so all batches SHOULD react with your receptors identically.
I see no reason for polymorphism to be relevant when discussing effects.

Exactly my point and what I've been saying. I just think people are searching for a reason as to why MXE can vary so wildly. In another thread there was proven to be a most likely psychoactive impurity in certain MXE batches....

 

[theacidtest]

Exactly my point and what I've been saying. I just think people are searching for a reason as to why MXE can vary so wildly. In another thread there was proven to be a most likely psychoactive impurity in certain MXE batches....

I feel like that's the area everyone should be focusing on- cuts and impurities. People's MXE batches are varying way too much to simply be set and setting and I find polymorphism to not be a logical explanation.

 

[Help?!?!]

I feel like that's the area everyone should be focusing on- cuts and impurities. People's MXE batches are varying way too much to simply be set and setting and I find polymorphism to not be a logical explanation.

Me to, point on! I feel like it's just people wishing and looking for an easy explanation!

 

[atara]

LSD binds only one way to the receptor. If a change in molecular conformation affected the pharmacokinetics of LSD (it doesn't), the only noticeable change would be in the potency, not the effects profile. Consider e.g

http://www.designer-drug.com/pte/12.162.180.114/dcd/pdf/azetidine-lsd.pdf

We know ketamine has stereoisomers which are the same structure in a mirror image. Here we see two batches of crystalline ketamine. User reported different effects from each batch. At first it seems that the left is racemic and the right is a single isomer. However, what we are looking at are polymorphs NOT isomers! You can't see an isomer and you can't see purity, but you can see a polymorph. The structural orientation of stereoisomers on a molecular level are mirror images, while the structure of molecules packed together into a crystal is the polymorph.

Extraordinary claims require extraordinary evidence. It's remarkably unlikely that the crystal of ketamine affects anything but the density (hence potency). Also, crystals from an isomerically pure substrate definitely look different from racemic... If you can find an image, you can probably link the thread.

 

[Crashing]

LSD binds only one way to the receptor. If a change in molecular conformation affected the pharmacokinetics of LSD (it doesn't), the only noticeable change would be in the potency, not the effects profile. Consider e.g

http://www.designer-drug.com/pte/12.162.180.114/dcd/pdf/azetidine-lsd.pdf


Extraordinary claims require extraordinary evidence. It's remarkably unlikely that the crystal of ketamine affects anything but the density (hence potency). Also, crystals from an isomerically pure substrate definitely look different from racemic... If you can find an image, you can probably link the thread.

I agree. I believe there may be isomers of MXE but i don't think the shape of the crystal (polymorph) has anything to do with which isomer it may be.

 

[Jesusgreen]

A lot of people are automatically assuming the currently completely unfounded assumption that polymorphism not only would affect potential solubility/potency of a particular sample of say LSD or MXE but also the effects profile in a way that dose alteration alone would not. I sincerely doubt that if this is actually the case that the difference would be significant enough to ever be possible to determine from the mere wildcard variable that is ever present with psychedelic/dissociative substances and results in many a trip that seems very unlike previous trips even if a similar dose/purity/setting is taken into account.

The first time I heard this discussion brought up was by a vendor themselves who seemed to be selling somewhat mixed purity batches of MXE, and seemed to be using it as an excuse for the hit and miss effects of their batches, I don't think there's any reason to assume it actually has much place in recreational drugs and their effects. Though I'd be curious to know exactly just what subtle differences such crystalline structural changes can have.

 

[Help?!?!]

This is exactly what I'm talking about, it's just a poor mans excuse!

 

[Toz]

I think we have enough myths about drugs and their effects.

 

[Solipsis]

Regardless of verity or better said relevance and significance for the average tripper.... the topic of discussion itself is "PD approved" and centralized. Myth or no, let's hear everyone's side and good arguments so that we can do scientific inquiries and decide for ourselves what to do with this info.

 

[Doldrugs]

I don't see anything about different effects from different polymorphs, but it's hard to find straightforward information on the phenomenon. What I do see is solubility and bioavailability being affected:

Polymorphs of a drug substance can have different apparent aqueous solubility and dissolution rate, when such differences are sufficiently large bioavailability is altered and it is often difficult to formulate a bioequivalent drug product using a different polymorph.

http://www.fda.gov/ohrms/dockets/ac/02/briefing/3900B1_04_Polymorphism.htm

It doesn't seem like different polymorphs would feel "cleaner" or "warmer" or anything like that, but maybe in tandem with active metabolites, contaminants, or precursors a slower dissolution and/or worse bioavailability could result in the other active materials having a stronger subjective effect? That seems like a reach, though.

 

[FnX]

I would like to chime in with some speculation of my own.

I believe that, even though different polymorphs result in different crystal structures, the structure in itself is largely irrelevant to possible variance in effects. Rather, I would speculate it is whatever is causing the molecules to form these different polymorphs what's causing the varying subjective effects and physical properties (like some polymorphs of paracetamol are more compressible when you press them in to pill form than others and some drugs have differences in solubility between different polymorphs). What is it then that causes polymorphism? Perhaps there could be, for reasons science is not aware of yet, differences in the electrical properties of molecules? As far as I know, these properties are largerly theoretical and determined by calculations instead of actual measurements. Perhaps such electrical differences could cause the molecule to activate it's target receptor in slightly different ways?

What really boggles my mind is, in the case of Ritonavir, according to wikipedia (it cited an actual study but I do not have full access to it) even a tiny amount of the inactive polymorph somehow appeared to convert potentially large stockpiles of the active polymorph to the inactive one when in contact with each other.