Sciencemadness Discussion Board

Cannabinoids - EPC & DHC Ethanolamides

un0me2 - 21-9-2010 at 03:05

the n-acylethanolamides of both the 0-3 Polyunsaturated acids from fish oil, are listed as CB1 Agonists (about 10-20% the strength of anandamide). As tuna oil is hardly difficult to find and these two make up about 30% of the total oil their isolation shouldn't be too hard.

Given a two-step process, saponification with aqueous base should get rid of anything but fatty acids. The ones we want (plus some we don't, they don't have agonist/antagonist action so I suppose they could be ignored) will form a urea adduct and precipitate.

I seem to remember seeing at least one file where ethylene glycol was efficiently monochlorinated in the presence of AcOH.

Attachment: Karaulov.etal.Synthesis.of.Fatty.Acid.Ethanolamides.from.Linum.Catharticum.Oils.and.Cololabis.Saira.Fats.pdf (165kB)
This file has been downloaded 2113 times

Attachment: Sheskin.etal.Structural.Requirements.for.Binding.of.Anandamide.Type.Compounds.to.the.Brain.Cannabinoid.Receptor.pdf (298kB)
This file has been downloaded 690 times

Attachment: Ratnayake.etal.Preparation.of.O3.PUFA.Concentrates.from.Fish.Oils.via.Urea.Complexation.pdf (630kB)
This file has been downloaded 1333 times

Any way you look at it, concentrate the fatty acids and form the ethanolamides of them and you'll have a fish oil supplement that WILL help with pain.

[Edited on 21-9-2010 by un0me2]

Globey - 21-9-2010 at 08:34

Here, I think you need to clearly differentiate between CB1 & CB2 effects. Then, is the amide active orally, and if so, is it only active at site (stomach, assuming you are swallowing cap fulls of the wax) where CB1 receptors are expressed. This is why just because something is a CB1 or CB agonist, it won't necessarily get you baked.

A very simple synth is to reflux olive oil and urea. You will get a whole lot of oleamide, plus a bunch of other amides. Oleamide I believe is a sleep inducing hormone which accumulates in the human spinal chord upon sleep deprivation. It is being investigated as such. And also as an anti-depressant. The patent does not make clear the mode of administration.

[Edited on 21-9-2010 by Globey]

kclo4 - 21-9-2010 at 13:40

Quote:
A very simple synth is to reflux olive oil and urea. You will get a whole lot of oleamide, plus a bunch of other amides.


Bullshit, have you tried it?
I have tried it, doesn't work.... unless you have different experience?

first off -- nothing is there to reflux - the urea decomposes into cyanuric acid (and other stuff) and ammonia, and the olive oil does not react, or boil, etc since urea decompose happens at such a low temp. adding it to hot oil is not safe for this reason, as it generates a lot of gas.

I believe the best way, though I never got around to doing it - so beware -- is is to do the basic bioldesiel procedure/trans-esterification with methanol and olive oil forming glycerol and methyl oleate.

The methyl esters than react with a conc. Ammonia solution to form the amides after a long-ish period of time... the solids can be separated from the liquid and be further purified. I believe their is an orgsyn references on this, though I could be mistaken...


Anyways, getting into the BBB is a trick, and preventing it from being metabolized as also a trick, but I believe FAAH inhibitors are as common as tylenol. And derivatives can be made easily...




un0me2 - 22-9-2010 at 06:07

Can't say I'm normally that interested, but I am struggling with chronic neuropathic pain and really don't like the idea of rubbing fucking chili on my arms (TPRV, heat triggers & pain receptors that fuck up, yip-fucking-ee). The alternatives are THC which I won't touch and the N-acylamines (N-arachidonoyl-dopamine looks interesting, but the acid ain't that easy to find), the related acids therefore might be of interest.

Interestingly, the NMDA Receptor (almost certainly not what you think) might be worth looking at, although the use of Pb as an antagonist might be rather problematic in the short-medium term, DXM looks like a likely trial target (OTC), Tramadol, Methadone & Ketamine have been thrown at it, they worked but the side effects suck, Codeine does SFA.

Never seen that indication of DXM before, interesting... I know Tramadol works to reduce opiate withdrawals to fuck all, I may just have spotted the reason.

Chainhit222 - 22-9-2010 at 06:16

what about good old pcp?

stygian - 22-9-2010 at 07:13

Quote: Originally posted by un0me2  
Can't say I'm normally that interested, but I am struggling with chronic neuropathic pain and really don't like the idea of rubbing fucking chili on my arms (TPRV, heat triggers & pain receptors that fuck up, yip-fucking-ee). The alternatives are THC which I won't touch and the N-acylamines (N-arachidonoyl-dopamine looks interesting, but the acid ain't that easy to find), the related acids therefore might be of interest.


You're probably already aware of this but it has been suggested that arachidonoylphenolamine contributes to the activity of tylenol. So some apap could also be an interesting amine to try.

stoichiometric_steve - 25-9-2010 at 21:21

Quote: Originally posted by un0me2  
really don't like the idea of rubbing fucking chili on my arms


Why not? It is a proven method, and if you really suffer that much, you would not deny easy and available treatment.

Nicodem - 26-9-2010 at 01:01

Where did this myth that these fatty acid amides are psychoactive initially originated from?
It keeps on reproducing all over various internet forums, yet nobody ever gives a reference, except maybe for a paper or two where intracerebral or intraspinal injections caused some response in the unfortunate animals, which obviously says nothing about their oral activity and bioavailability in general. Good to moderate receptor affinity and demonstrated agonist activity are not enough to prove a compound is also psychoactive. These are fatty acid amides and there are plenty of enzymes that promptly deal with such substrates, and there are also a few other issues with them that might limit their bioavailability, so it seem pretty much counter-intuitive to expect any activity at all. Yet nobody bother to give a reference for claims of psychoactivity. Besides, certain arachidonic acid amides are the ones that have good enough affinity at CB receptors and arachidonic acid is extremely expensive. It and its derivatives are labile and decompose on prolonged exposure to oxygen, light or room temperature - certainly not a moiety much useful for a potentially bioactive compound.

Like kclo4 said, urea is long gone at the time the olive oil reaches its boiling point, at which it furthermore starts decomposing - to the carcinogenic acrolein among other things! On the other hand, heating fatty acids with urea at 120-150 °C does give moderate to good yields of fatty acid amides (there are some old articles describing the process). Other fatty acid amides are easily prepared using the general Org. Synth. method. Heating the reactants neat at about 200 °C can also give moderate yields in some cases where the substrates are robust enough, but obviously the boric acid catalysed coupling is way more efficient yield-wise and reaction conditions-wise. Aminolysis of the fatty acid methyl or ethyl esters seems like an unnecessary fuss given the alternatives, but it is also a viable method, though it only works with enough nucleophilic amines (so it does not work with anilines or sterically hindered amines). Actually all this is so simple and many fatty acids are very cheap or can be made from oils, soaps or the like, that I don't see why not rather preparing these amides rather than discussing their potential activity - it is after all an interesting experiment from OTC materials.

un0me2 - 27-9-2010 at 01:31

Activity per se is not really that interesting to me, other than the extent to which they may or may not slow down hydrolysis of the endogenous amides. The synthesis of the relevant amides from urea doesn't appeal, after all it is the ethanolamide or the monoglyceride that is of interest, not the acid amide itself.

I think the use of the esters is only indicated where the multiply unsaturated oils (given the care taken I rather suspect there is a real risk of isomerization) are being converted to the amides. I have no idea if there is any necessity to use such care (ethanolamine isn't that strong a base anyway is it?), nor do I much care.

Also, DXM is fairly useful, suprisingly enough it provides far more pain relief than 240mg Codeine / day, which is interesting. It would seem to confirm the involvement of the NMDA Receptors in the process (at least in my case, or a placebo effect), given that the less potent DXM is more effective, at a lower dose, than codeine.

PS As to the activity & SAR of the fatty acids, I attached one of the VERY few papers I could find on the subject above. Where everyone is getting their data from I'm fucked if I know. As the activity is not restricted to the brain, but also exists in the peripheral nervous system, I'd be interested to see if the BBB is as big an issue. All I'd take from the paper is that if anandamide is the putative reason for chocolates supposed "activity", then it would have to be orally active. How much so is not clear.

PPS Steve, I have few pain receptors on the surface of the skin that work (numbness is a primary symptom of nerve damage, particularly where trauma is involved), that means the effectiveness of chili in desensitizing the nerve endings would be effectively nil, while the potential for doing harm is no lower than before (actually it would be raised by insensitivity). Capsicum spray was not properly evaluated (according to several papers), it was pushed through without complete testing due to its strangely high-toxicity to lab-rats. How toxic it is over time to people, how it is absorbed and what effects it has, those boxes have yet to be ticked.

The actual diagnosis is "Reflex Sympathetic Dystrophy" (aka "Causalgia" or "Complex Regional Pain Syndrome"). There is damage to the nerves and the "pain" signaling is not related to what happens to the upper level of the epidermis (as is usual), the "pain" being signaled to the brain is not real, the nerve is effectively being short-circuited and sending signals that bear little/no relation to actual events. On top of that, the numbness of the skin is because the nerve is not "effectively" (or where skin grafts are concerned, physically) or "properly" connected to the neural network.

[Edited on 27-9-2010 by un0me2]

Globey - 27-9-2010 at 06:18

despite all the raw hatred here, I can get anyone some neat oleamide (prilled waxy substance) free of charge. The chemical is neither watched or suspicious, and as I understand it, giving something away (versus offering for sale) is a further way of helping to insulating one's self. Want some oleamide, drop the paranoid act, and PM me your addy, I'll Priority you a kilo. And STOP it with all the fucking hate, you fucking hate mongers. Your all like my wife, but it's as if her period stopped a week before it's about to start, and remains there, at her most "steroidial". Get off the rag. Get rid of the flustered French Chef. Just drop it. It's annoying, immature, and further more, abrasive. To me, it's a non-starter. Thanks for your understanding.

Globey - 27-9-2010 at 06:22

un0me2,

It'd s certain type of pain (wind up?) the nmda antagonists are more effective against than opioid agonists. Also, anti-depressants, anti convulants, they all seem to respond best to this sort of pain from what I seem to gather.

Sedit - 27-9-2010 at 17:52

Quote: Originally posted by Globey  
despite all the raw hatred here, I can get anyone some neat oleamide (prilled waxy substance) free of charge. The chemical is neither watched or suspicious, and as I understand it, giving something away (versus offering for sale) is a further way of helping to insulating one's self. Want some oleamide, drop the paranoid act, and PM me your addy, I'll Priority you a kilo. And STOP it with all the fucking hate, you fucking hate mongers. Your all like my wife, but it's as if her period stopped a week before it's about to start, and remains there, at her most "steroidial". Get off the rag. Get rid of the flustered French Chef. Just drop it. It's annoying, immature, and further more, abrasive. To me, it's a non-starter. Thanks for your understanding.



What the hell are you talking about? For once no one is hating on a thread discussing a pychoactive substance and yet you still have to start in. Stop and stop now. I want to see this thread progress and im sure you do as well and I think as it stands you staying quite would be the best course of action.

If possible I wish the MODs could delete my post as well as his hate filled post.