What potential does DMSO have then?

[vecktor]

If you look at "Physical Chemistry" by W.J. Moore, 4th edition, page 257, you'll
see a phase diagram for nicotine + water. It shows a large two phase region
above 60 C extending from ~5% to 80% weight % nicotine. This suggests that steam distillation can be used to obtain a pure product. Others might suggest
extraction with an organic solvent. The problem is that such an extract would
require a purification step. Many low molecular weight oils which are insoluble
in water can be obtained in nearly pure form via steam distillation. Steam
distillation works well with low molecular weight amines when the still pot is
made basic with hydroxide. Addition of base might be helpful in steam distillation of nicotine. Sorry I can't supply a documented procedure on short notice.

DMSO will dissolve just about anything and certainly tetrahydracannabinol, caffeine and nicotine. DMSO is well know for its ability to carry solutes through the skin.

how do we get to nicotine from a question about DMSO? am I missing something?
Anyways most nicotine containing products like patches contain nicotine salts, so base would be essential for liberating the freebase.

On the subject of DMSO there was an infamous incident of the TOXIC LADY in west coast America where a patient presented to ER, and was extremely sick and then died after using DMSO as a muscle rub, the ER staff treating her collapsed and so did several bystanders. one theory for the toxic woman was proposed ,I think by los Alamos, was that the DMSO had somehow become oxidised by her to Dimethyl Sulphate, rather unlikely IMO. More likely some one packing the DMSO got the two chemicals mixed up. still an interesting story..
http://www.gasdetection.com/MDS/m092198.html

 

[FJ22]

I just read somewhere else about DMSO + Salvia D extract, so I'll just quote it here:

DMSO tastes evil. EEEEvil. But the tincture works. SWIM reports that it took him to outer space and back. It works just a bit slower than smoking, and because Salvinorin-A is so soluble in DMSO (23mg/cc at room temp) you only need a tiny bit of tincture.

SWIM prepared the tincture as follows: he mixed 1g of 25X (estimated to have 50-70mg of Salvinorin-A) and 5cc of DMSO 70% (the rest is distilled water) in a 10cc brown dropper bottle. Assuming complete extraction of the Salvinorin-A, each cc of the tincture contains 10-15mg of Salvinorin-A. The color of the tincture is an extremely dark brownish green. In addition to the evil taste of DMSO, it is also very bitter

SWIM dripped 0.2cc of the evil smelling DMSO+Salvinorin-A on to his tongue, and within 1min he was gone; at the last possible moment he spit out the DMSO+saliva into a glass of water and lay back on his bed in total darkness. The experience lasted about 22 minutes clock time, but SWIM says it felt like hours and hours. CEVs and OEVs, no entities though, and strangely, this trip also involved "smelling" of colors and sounds -- probably on account of the horrible taste in SWIM's mouth.

When asked, SWIM said that he'd probably try to spike the DMSO with some kind of mentholated product. That might reduce the horrible taste to a bearable level. Another possibility is diluting with water, although that might make the Salvinorin-A less soluble and less transportable across the mucal membrane. Finally, SWIM is considering delivery via rectal gel-caps containing the DMSO -- the problem there is to find a gel-cap that will reliably hold such a tiny amount of fluid.

Just thought you'd all like to know.

 

[PlurredChemistry]

if you're going to try transdermal stuff, scrub the area you'll be using on before applying the dmso solution.

 

[kidamnesiac]

"Revisiting Bicycle Day" by Dave Nichols

Another fact: I've made LSD in my lab on many occasions for research purposes, possibly in not so meticulous a manner as Albert Hofmann. Nothing ever happened. I had several graduate students who made LSD as an intermediate for projects. No accidental ingestion of LSD ever occurred. A technician in my lab makes it routinely because we use it as a drug to train our rats. He's learned by experience that he never gets high, nothing ever happens. And yesterday I was talking to Nick Sand, and Nick said, "I made a solution of LSD in DMSO…" -- DMSO (dimethyl sulfoxide) is a chemical that greatly enhances absorption of other chemicals through the skin -- he says, "…I painted it on my skin. Nothing happened." A concentrated solution and nothing happened! How did this very meticulous Swiss chemist get the LSD into his body? I don't know.


That is a fantastic read, highly recommended

 

[Ham-milton]

Suggesting that it might be more exaggeration than truth? I dunno- somehow he figured it out!

 

[WarrenZevon]

DMSO - A Rational Use?

i dont know why people really care about transdermal anyway, its unlikely to be an especially fast method of administration compaired to any others, the only advantage i can think of is it can be used for sustained release. i have also experimented with DMSO, the only promising idea i have had so far was the combination of sublingual administration and dmso, because it would enter the blood stream quickly, eliminate the need for needles and might even overcome some of the mono amine oxidase issues that drugs like DPT and DMT have orally.

best ideas i have had so far are oral salvinorin-A in DMSO solution, could be incredibly potent (as potent as smoking prehaps) and with a much longer duration, giveing the user proper ammounts of time to explore salvia space.

also DMT in dmso sublingually, or a combination of dropping a lower dose of any given drug combined with DMSO up the nose. i find just the simple act of making a powder a liquid before snorting it make it much more potent, i dont know if anyone here has done a line of coke, waited till you were coming down a little, snorted a bunch of water and gotten a second rush.

A quick aside. My few experiences with LSD were - nothing less than mystical. Today, several RC's are cheap, simple and fit on a blotter. They are however - soulless. I mourn the reality that I will never experience LSD again. While I would take LSD over Cocaine any day - the market dictates what is accessible to me. Cocaine or fake 'x' get delivered to my door.

To the point: Sublingual or Intra-nasal cocaine + DMSO would seem ideal for those of us who wont IV or smoke it.

ANY real world experiences with this?

Would that make you deathly ill?
How bad could it be VS the burn of salvinorin, nausea of LSA or San Pedro?

Experiences?

wz

 

[WarrenZevon]

Suggesting that it might be more exaggeration than truth? I dunno- somehow he figured it out!

I believe it is a VERY LONG STANDING (and possibly nobel) tradition for the 'medicine man' to experiment - first - upon himself.

Why would a man with Hoffman's skills risk damage to his career (by claiming for example - that he has isolated a profoundly potent compound - at doses as low as micrograms) until he could replicate and CONFIRM his breakthrough?

LSD was referred to as his 'CHILD'.
He later became an elite psychonaut.
Like any 'child' - it must first be conceived!
He stresses that his child was much less the result of some 'accident' than the result of his considerable labor (of love).

Is it so hard to believe that Hoffman conceived of, intended to, isolated, tested, then replicated his test - all in the service of creating such a profound compound?


wz

 

[Ham-milton]

Yeah, it is. Unlike today, at that point in time very little was known about psychedelics. I don't think psilocybin's structure had been determined at that point.

He had no reason to suspect that it was a psychedelic. Other compounds in its class may have produced "psychedelic effects"- but at that point it was believed to be poisoning, related to all the other bad effects ergoloids produced. No one realized that the visuals caused by St. Anthony's Fire were serotonergic or related to other psychedelics.

He didn't have structure activity relationships to go on to suspect that LSD was a highly potent psychedelic. No one did.

Say that Psilocybin, DMT and Mescaline's structures were all known at that time (I don't know if they were or weren't, I think DMT came in the mid to late 50s). If you would have looked at those structures and compared them to LSDs, would you have said "Oh boy, there's a connection- this is gonna be a psychedelic too!" ???

Not likely. The idea that PEAs and Tryptamines and Ergoloids were all related didn't occur before that date. The first time I ever heard of it was in FnB's thread on the subject. I don't know that Shulgin or Nichols connected the two.

 

[dorothyperkins]

http://www.erowid.org/references/refs_view.php?ID=2904

1973! why didn't he brominate it?!

Edit: Oh, he did the DOM analog!

http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6518

 

[Bondmaker]

mental notes

First of all, if you've made LSD you are going to get off on it no matter how it gets into the bloodstream. DMSO will dissolve nearly anything organic with even a high molecular weight, it is the solvent of last resort for getting things to dissove to put in NMR tubes to get a spectrum on. I say last resort because here we use deuterated DMSO which tends to exchange with acidic protons and so you only see them as broad bands or "smoother out" and not well integratable, or not at all.
Now it's physiology. DMSO disturbs the skincells and disrupts the lipid bilayer to the extent that the bilayer lets the dMSO (and anything that it's carrying) penetrate into the dermal capilliaries and eventually into the larger bloodsteam, however, once the compound gets this far, it is diluted out by the cytosol, and if extremely water insoluble, it will probably just "glomb onto" something and get eliminated, and/or even if it makes it to the bloood/brain barrier, there is the question of will the compund pass through. DMSO in large amounts is used in animal testing of very insoluble compounds, but this is usually as a "last resort". For CNS active compounds,a lot of DMSO has to be used; it is one of the only things that disrupts the blood-brain barrier, often enough to let very water insoluble small molecules to pass through. It need not be said that this is a last resort for testing CNS actives as it raises the question of, well even if they are CNS active , we can't sell them as injectibles in 10 or 20 mL of DMSO8) .

 

[WarrenZevon]

He had no reason to suspect that it was a psychedelic. Other compounds in its class may have produced "psychedelic effects"- but at that point it was believed to be poisoning, related to all the other bad effects ergoloids produced. No one realized that the visuals caused by St. Anthony's Fire were serotonergic or related to other psychedelics.

Time out - I am not suggesting anyone knew the structures or mechanism of action of known psychedelics. Nor that the structure of LSD was inferred or came to Hoffman in a dream...

Did they have any naturalistic explanations for the confounding varieties of documented 'visions' or any psychoses?

Dear God No!

Was our enlightened Hoffman hoping to discover a 'psychedelic'?

By definition such would be impossible. But this is a matter of inaccurate medical semantics.

In those unenlightened times - what we call 'psychedelic' was understood as a toxic psychosis - or as a 'psychotomimetic'.

So what DID they know?

These guys knew of the visuals, psychotropic, even 'psychotomimetic' features of St. Anthony's Fire (as well as all the other toxic effects associated with ergoloids).

And why were they working at all with ergoloids?
Because as pharmaceutical innovators they knew that isolated 'poisons' - taken in low enough doses (and derived from organic sources) were - by definition - pharmacologically active!

Surely Hoffman and Sanofi understood the probable pharmacological gold mine ergoloids represented?

Would they not try to isolate any potentially marketable effect from the ergoloids? Would they ignore the dramatic psychotropic effects?
Surely not.

Why not intentionally experiment on yourself - as is an honored tradition among the ingeniously curious (leading to countless other discoveries) - especially if you are taking what you believe to be homeopathic doses?


wz

 

[Ham-milton]

These guys knew of the visuals, psychotropic, even 'psychotomimetic' features of St. Anthony's Fire (as well as all the other toxic effects associated with ergoloids).

And why were they working at all with ergoloids?
Because as pharmaceutical innovators they knew that isolated 'poisons' - taken in low enough doses (and derived from organic sources) were - by definition - pharmacologically active!

Surely Hoffman and Sanofi understood the probable pharmacological gold mine ergoloids represented?

Would they not try to isolate any potentially marketable effect from the ergoloids? Would they ignore the dramatic psychotropic effects?
Surely not.

Why not intentionally experiment on yourself - as is an honored tradition among the ingeniously curious (leading to countless other discoveries) - especially if you are taking what you believe to be homeopathic doses?


wz

But you're presenting a view of history that just isn't the case.

Ergoloids never presented to be anything of a "gold mine" prior to the discovery of LSD. They had limited uses as oxytocic's in child birth. I don't think that they'd even been used in migraines at that point.

You're trying to apply motives to an event for which there is no evidence that they existed. After all this time, I'm pretty sure Hoffman would have come clean if he'd been experimenting on himself. However, if it was something stupider than it absorbing through the skin, I don't see him admitting that. The Bike story sounds a lot better than accidentally inhaling a bunch of powder through carelessness.

 

[WarrenZevon]

But you're presenting a view of history that just isn't the case.

Ergoloids never presented to be anything of a "gold mine" prior to the discovery of LSD.

I am afraid I must not have made myself clear on this point.
I am not claiming that ergoloids were 'giving away', shedding or 'presenting' any one with free and easy medications!

That is just not how the business was done in the old days.

The once innovative drug companies had to identify highly pharmacologically active organic compounds. Such active compounds are where the drug companies rationally invested R&D dollars, blood, sweat and tears.

Exceptionally pharmacologically active compounds were the most rational place to risk investing such R&D.

Ergoloids are profoundly pharmacologically active.

Sandoz was not mining ergoloids for any other reason than to turn a profit.

You're trying to apply motives to an event for which there is no evidence that they existed.

Well, you are of course correct.
I was not there (Damn! Damn! Damn!).

I confess - I wanted to find a hero in Hoffman. With so many unknowns, my preference was to paint in the blank spaces the impression of a hero.

May I rant off-topic for a bit?

Such R&D risks are not taken in the industry today.
BigPharma spends precious little on innovative R&D.

'Me-too' analogues, extended patents, aggressive PR and (VERY AGGRESSIVE) marketing along with the most powerful lobby in DC is what keeps them the second most profitable industry on earth!

wz

 

[Ham-milton]

I'm not saying that they didn't have potential profit in them, they certainly did, but there's a big difference in the earnings potential a drug like ergonovine has and things like Xanax and Lipotor and Norvasc have.

Of course there was potential to make some money off of oxytocics, but you can't even begin to compare it to that of the big drugs.

Again, though, theres a big difference in how pharmaceutical companies were making profits. That was before the days of the blockbuster pharmaceuticals and billion dollar profits, but even still, the point remains valid. Oxytocics are "niche" drugs- they're never used outside half of the population, and even then, they're only applied to women who are actually in the process of giving birth.

You can't expect a drug designed to make the birthing process simpler- where patients are given less than 5 doses in their lives- could ever turn much of a profit. Economics is way outside my field of study, but even I can see why they'd never expect to get rich of of these drugs. And indeed, no one has.

LSD wasn't even being looked at for human use- but just as an intermediate.

Hoffman is a hero. He didn't have to discover LSD through noble intentions, and consider his post-LSD work. He's definitely a hero for psychonauts everywhere.

 

[psood0nym]

I've read of DMSO being used to make the BBB more permeable to drugs. I assume this works through DMSO binding to certain types of drugs and changing them into more compact shapes or some such mechanism--but I really don't know. I'm wondering if a drug like ephedrine, whose unpleasant higher dose effects are thought to be due to its inefficiently crossing the BBB and thereby having its effects mostly localized to the body, might be made into a more pleasant substance by dissolving it in DMSO and taking it orally (or otherwise.) It seems potentially dangerous but I wanted to check to see if it seems at all feasible. Quoted from wikipedia:

Ephedrine increases serum dopamine levels minimally in comparison with an equivalent dose of dextroamphetamine (Dexedrine®). Dextromethamphetamine (Desoxyn®) raises dopamine levels dramatically (more than two times that of an equivalent dose of dextroamphetamine). This supports the general consensus that ephedrine has more of a peripheral action on the sympathetic nervous system, whereas amphetamines appear to cross the blood brain barrier more freely and tend to have a stronger central action.

 

[Bondmaker]

the real story..

of Hoffman's "child" is more like an "accident". Back in those days, doing organic chemistry was difficult as they had very poor to no "useful" electronic instrumentation for structural elucidation. "Degradation and synthesis" was the technique of the day. For rellatively complex molecules like Lysergic acid, first they would get the major alkaloid from extraction of the raw natural product (in this case "ergotamine" from the mold "claviceps purpuraea" that grows on rye)
http://medicine.cug.net/drug/02/structural_formula/ergotamine_tartrate.png
And the first thing that they would do is a degradation to produce a large amount of "a carboxylic acid fraction" and a "basic amino" fraction along with whatever came out in the "neutral fraction". Well anyway, they got gobs of purified lysergic acid (which was surmised to be "pure whatever" by just a sharp melting point, they may have some "wet chemistry tests to determine basic funtionality, like is it an alcohol, an amine or a carboxylic acid, and maybe, if they were lucky an IR or a UV spectrum) which they would then try to figure out the structure by boiling the compound in acid or base or some other method to degrade the lysergic acid into smaller pieces which they would then try to find the structure of the pieces by synthesis and comparing what they had with what they knew they had. It was very exhausting and difficult work; all these men and women were "heroes" to us modern day nads who go about our work taking 500mHz NMR spectra and even get a crystal structure in a few hours. Well to make a long story short, Hoffman was doing simple "Derivatization" studies. To prove that their was a carboxylic acid, you would make a series of amides from simple amines. The "neutrality" of the amide derivative was sure enough proof that you had a carboxylic acid, but that's all you knew. Also, because they knew the rudimentary properties of the natural product, by making derivatives, they just may hit on useful pharmaceuticals, to be marketed after they had fully elucidated the structure, or they could just call it "lysergic acid diethylamide" and market it as such, much like the drugs cocaine and morphine were marketed before anybody had a clue of their structure. It would be safe to say that Hoffman was looking at the amides of lysergic acid, as putative anti-migraine compounds, and that he already knew the structure of lysergic acid. Back in my early lab days, it was not uncommon to find bottles of pure lysergic acid on the shelf in the chemical storeroom, as it is so easy to produce from the natural procuct, if you were any good in the lab, like our "heros" of the past. To make the diethyl amide, they didn't have the easy "peptide coupling reagents" that we use nowadys to make clean amides, they had to use the old nasty thionyl chloride method which if not done carefully could mess up your molecule, especially if it had a lot of functionality or/and wasn't the most stable beast to begin with.

 

[vecktor]

Fortune favors the prepared mind.....Pasteur

There is no doubt that the discovery of the structure of ergotamine, and therefore lysergic acid and then all the derivatives was a mammoth piece of work which had been going on since the turn of the century,
there was potentially vast money in the use of ergot compounds in childbirth as oxytocics, the issue with unpurified ergotoxine as used was that the activity was variable and there was other materials in it which did not neccessarily add to the beneficial effects. It was long known that the ergot alkaloids on the whole consisted of a amine part and a acid part, indeed lysergic acid is named after LYSis of ERGot. the structure of lysergic acid was pretty much known all bar a few details.
The structure of dihydrolysergic acid was known before 1938 the position of the double bond in lysergic acid was in dispute for some time but jacobs correctly identified it as being in the 9-10 position in what he called isolysergic acid, and in 1945 dihydrolysergic acid was synthesised by Uhle and Jacobs.
Fundementally though the only absolute proof of a structure of a natural product is total synthesis, lysergic acid I believe was first done by Kornfield, Woodward et al in the mid 1950's.

So it was very logical to make a series of amides with different amines to see if they retained the desirable action whilst perhaps perhaps being cheaper or less toxic. It was also desirable to be able to convert less desirable ergot alkaloids such as ergocryptine into more desirable ones like ergotamine and ergonovine. It was also desirable to improve the methods of coupling lysergic acid to amines, the hydrazide route being favoured at the time, sandoz was able to develop much improved methods.
Hofmann was part of a massive team at Sandoz, they had state of the art equipment for the time, and they had the resources and time to tediously fractionally crystalize various ergot components, then degrade them to determine the structure. they also had the advantage of swiss 'neutrality' in the war, they didn't lose their scientists to war programmes.

There is a great review on this by Arthur Stoll one of the forgotten heroes and is well worth reading.
http://designer-drugs.com/pte/12.162.180.114/dcd/pdf/ergot.alkaloids.chem.rev.pdf

What strikes me as odd,if you believe the mythology, is that the diethylamide which is pretty much the only amide which has the extreme hallucinogenic potency, was chosen for resynthesis on a hunch, what seems more likely is that someone in Sandoz discovered the activity and passed the information to Hofmann who was in a position to lobby for its resynthesis. and changed the perception of ergot alkaloids forever

The most profitable and important product to come out of Sandoz and Hofmanns work is Methergine (methylergonovine) he is famous for his sorgenkind yet methylergonovine has made arguably a bigger impact.
this is now well off topic
I would love to get access to the sandoz archives, if anyone can help me PM me

 

[kidamnesiac]

there is a massive review on the structural determinations and other intensely chemical view of the ergoloids by a fellow at purdue (i think, unless it was iowa) from the late 70's. I believe the review is 50ish pages

 

[fastandbulbous]

Well in Scrabble, you can maske 'mods'!

Quoted from wikipedia:

In light of some of the things I've seen written in Wikipedia recently, I'd say without a supporting reference from say a scientific journal, I'd take what's said with a hypertension creating dose pinch of salt...

 

[ex-amine]

What strikes me as odd,if you believe the mythology, is that the diethylamide which is pretty much the only amide which has the extreme hallucinogenic potency, was chosen for resynthesis on a hunch, what seems more likely is that someone in Sandoz discovered the activity and passed the information to Hofmann who was in a position to lobby for its resynthesis

I don't think it was a someone , but might have been a some-mammal (rats) that showed unussual activity which might have given Hoffmann the hunch to look at the 25th compound again.