The Small & Handy Polymorphism Discussion Thread

[Crashing]

Why has the presence of polymorphism never been mentioned when considering the classic 'good vs. bad' acid?

 

[pupnik]

how can we tell?

 

[theacidtest]

Polymorphism should have nothing to do with the effects of a drug. I know all you MXE heads will disagree, but that's just how chemistry works. Different isomers, yes, but polymorphism simply refers to crystal structure.

I started out not believing in differences between batches of LSD. After having eaten a LOT of acid my opinion has changed. But there is no legitimate scientific reason currently known that would explain this phenomenon. For the time being, scientifically, LSD is LSD regardless of what conclusions we may come to from personal experience.

 

[Ismene]

I've had a good LSD trip from the first 4 blotters in a strip, then bad LSD from the next 4 blotters in the strip. Unless someone is dousing them with different LSD I think LSD just has a vast range of effects including both "bad" and "good".

 

[Solipsis]

Agreed with theacidtest. When the crystal dissolves any 'morphisms' are lost so it shouldn't matter anymore.

I guess a good suggestion, but the rest of the debate really belongs in the dirty acid debate / faq-in-progress (sigh) thread..
okay to close this or does anyone have grounds for further discussion?

 

[Crashing]

Well the whole idea of polymorphism is that the effects are definitely different. They found a polymorph of some anti retroviral drug to be inactive with one polymorph, active at another. They say the physical properties of a crystal determines how it will orient in the receptor. IMO that doesn't quite make sense but that's what 'they' say. And if you look at the molecular images it appears that molecules can be sort of twisted or bent slightly.

The reason for this thread is there seems to be a new understanding of polymorphism and i think we need to look further into this rather than just writing it off. Folks over in the MXE thread insist that there are differences in effects and there are medical journals that back up that claim. This is an idea i initially thought to be nonsense (i thought exactly the same as you Solipsis) but appears to have some truth. If that's the case, the same would be true for all drugs including LSD.

I'm traditionally someone who thought that batch differentiation was BS, but now i'm beginning to realize there may be truth to it.

There are links to my findings in the MXE thread, it seems to be a relatively new discovery and i hadn't heard of it until recently.

 

[Solipsis]

Alright, then someone needs to explain that claim I guess - or, I will try to find literature on it when I have time later, if I can. There are of course tons of publications some of which are worthless, so I am not very impressed in advance.

Still you are absolutely right that it deserves to be looked into.

I remember that apparently people even had nasty trips with sandoz vials of liquid LSD. So even besides the point that I have no idea what liquid acid would mean for polymorphism as there simply aren't any crystals... the explanation for the nasty trips happening just can't be 'there are different types, some of which are bad' whether that good or bad is related to polymorphism or not. Otherwise the bad experiences with the supposedly good stuff are not explained. Logically they are the same matter.

 

[Help?!?!]

Agreed with theacidtest. When the crystal dissolves any 'morphisms' are lost so it shouldn't matter anymore.

I guess a good suggestion, but the rest of the debate really belongs in the dirty acid debate / faq-in-progress (sigh) thread..
okay to close this or does anyone have grounds for further discussion?

This, to me overthought is basically useless, and none of the studies have to due with MXE.... Until then let's get talking!

 

[Solipsis]

Not sure what is being overthought rather than debated here, but I will take that over vague assumptions based on different batches feeling different somehow. Which is totally unscientific and the psychological component (thing placebo etc) is so disregarded... very tiresome.

I would ask if polymorphism may be related to epimerisation and isomerisation. The latter effects may remain even if the compound is dissolved. That would also mean that these effects only apply to compounds that can exist in different conformations. I guess LSD yes but arylcyclohexylamines like ketamine and MXE no I don't think so. You can't turn racemic K into S or R simply by reXtallizing it in a certain way.

Also, I was talking - kindly explain the illogic of Sandoz LSD still being able to cause nasty trips physically and mentally.. degradation? Only that maybe, doubtful

 

[donvliet]

It's very difficult, if not impossible, to deduce chemical properties just from the subjective experience of a trip. First there is obviously set & setting which can play a bigger role than many will acknowledge. Especially a substance such as LSD can provide very different experiences from one trip to the next.

Then there are other possible explanations to be eliminated before you can reach a conclusion. Things like residual chemicals from the synth, degradation products and even allergic reactions to the dye used on the blotter could all be playing a role. To really reach meaningful results, proper analysis needs to be done where you can control and/or eliminate as many possible variables.

 

[Doldrugs]

Yes, polymorphism is real. Yes, it's relevant to pharmaceutical science. One example:

In the case of the antiviral drug ritonavir, not only was one polymorph virtually inactive compared to the alternative crystal form, but the inactive polymorph was subsequently found to convert the active polymorph into the inactive form on contact, due to its lower energy and greater stability making spontaneous interconversion energetically favourable. Even a speck of the lower energy polymorph could convert large stockpiles of ritonivir into the medically useless inactive polymorph, and this caused major issues with production which ultimately were only solved by reformulating the medicine into gelcaps and tablets, rather than the original capsules.

http://en.m.wikipedia.org/wiki/Polymorphism_(materials_science)

If you're going to dismiss something outright, at least have the decency to do basic research on it first. I don't understand why the opposition to this concept is so virulent.

And to preempt wasting time with this tangent, no, affirming the existence and potential relevance of polymorphism is not the same thing as confirming that MXE and LSD are polymorphic and that the differences between people's subjective experiences with them are due to polymorphism.

 

[Solipsis]

The point is not whether polymorphism is real but whether it's relevant.

Ritonavir is a very different and complex sort of substance which apparently has polymorphic states that have very different solubility and therefore bioavailability...

Ever heard of batches of LSD or MXE that won't dissolve in water?

Again, it nothing should be rejected right away but so far the evidence just isn't corroborating polymorphism being the issue here with say LSD and MXE.

 

[Doldrugs]

If it were as simple as "when it dissolves polymorphism no longer matters" then why would polymorphism ever be relevant to pharmaceuticals? Wouldn't the inactive polymorphs just break up and become active when introduced into the body? But that's not what happens.

The point is not whether polymorphism is real but whether it's relevant.

I wish that were true, but whenever the subject comes up it seems plenty of people want to debate its existence.

 

[Solipsis]

^ I guess not if a rather insoluble crystal is formed that "breaks up" i.e. dissolves at a a very low rate and pushes the BA down making it relatively ineffective.

 

[Crashing]

Ok, if i understand correctly, Isomerism and Polymorphism aren't the same thing.

here's an image borrowed from a thread in 2010 ( i never read until now ) that I'm sure you remember:

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.

However, since appearance will not be indicative of stereoisomerism or purity, appearance means nothing. It seems you can have two different stereoisomers with the same crystal polymorph.

It seems to me that isomerism may alter effects in one way, while polymorphism will alter effects in another. A stereoisomer will fit into the receptor slightly differently, the same way a right hand in a left handed glove wouldn't fit perfectly. Then the shape of the crystal (polymorph) will, at the very least, affect the rate of absorption, thus creating differentiation in psychological response as the rate of metabolism changes.

I could be totally off but that's what i've gathered. LSD's isomers are all inactive, but pure LSD may exist in several polymorphs, potentially explaining the age old debate.

 

[perpetualdawn]

Is it possible (in general, not specifically with LSD) for a drug to have a polymorph where you end up with crystals of just a few molecules in size, so tiny that they appear to dissolve fully, and can still cross the various barriers in the body at ease (gut, blood-brain etc), but in fact still remain in tiny crystal form, and interact differently with receptor sites? Has anyone ever heard of this kind of thing? I'm just conjecturing here...

My personal opinion is that LSD is LSD is LSD and variances people claim are due to mindset etc.

 

[Crashing]

Well i think the reason the crystals form differently is because the molecules are slightly warped, so they would lay into the receptor slightly differently, thus have slightly different effects.

And thank you for title change.

 

[Burnt Offerings]

I guess it's an interesting discussion, but what practical implications are there for the average drug user?

 

[Crashing]

I guess it's an interesting discussion, but what practical implications are there for the average drug user?

I guess it was just a little research project, establishing that we can't judge a book by it's cover.

 

[Help?!?!]

Well i think the reason the crystals form differently is because the molecules are slightly warped, so they would lay into the receptor slightly differently, thus have slightly different effects.

And thank you for title change.

See yes and no. Different drying techniques can yield wildly different shape do, sized, and even colored crystals when it comes to some drugs.