This is a topic that interests me, So please update this thread with your posts on the other forums, if anything interesting pops up, I would like to see it.
Especially if it can be synthesized easily, is legal, and has decent activity/effects.
Here, these links, articles, etc might be useful, if you have not seen them already.
http://127.0.0.1/talk/index.php/topic,863.0.html ( Oleamide... )
http://127.0.0.1/talk/index.php/topic,91.0.html (Anandamide - a cannabinoid that may have recreational potential? )
http://127.0.0.1/talk/index.php/topic,337.0.html (Bibenzyl Cannabinoid from NZ Liverwort 'Radula marginata')
http://127.0.0.1/talk/index.php/topic,794.0.html (THC & Tropacocaine Otto Snow)

I think what might be just as useful as an analog of anandamide is a decent FAAH inhibitor,metabolized paracetamol produces a FAAH inhibitor, but I am unsure of how effective it is, as I believe I mentioned earlier, analogues of the FAAH inhibitor formed should be very easy to produce.

Anyways, back on topic - It seems like the most readily altered function when it comes to the anandamide structure is obviously the carboxylic acid. In lack of better terms...what part of the receptor does that fit in? If we can figure that out, perhaps we can make decent guesses as to what functional group would be best to add, such as amide, N-methyamide, esters of amines, etc..

I speculated that N-(2-hydroxyethyl)acetamide in analogous doses would produce anandamide as a metabolite (in vitro). If this was correct other cannabinoids could theoretically be produced (in vitro) providing inwatched precursors and methods.

Wow, Brilliant way to go about that! At least if this is possibly, I bet the aromatic ring plays a very important roll however, when it comes to its metabolism. Also one might have a problem with N-(2-hydroxyethyl)acetamide being possibly carcinogenic? I know acetamide itself is carcinogenic, however, I don't know anything about substituted acetmides.

The last link does not work properly for me, maybe double check it?

I speculated that N-(2-hydroxyethyl)acetamide in analogous doses would produce anandamide as a metabolite (in vitro).

Unfortunately, I suspect it doesn't work like that.

Just for the sake of this discussion, here is a link connecting the two posts, so there is more information on this link as well... http://forums.blacklight.me/viewtopic.php?f=32&t=1330

It isn't a prodrug, it inhibits FAAH. Read the links, etc

FAAH = Fatty acid amide hydrolase

I doubt FAAH inhibitors play a roll in anything with the classical type cannabinoids or JWH-018, but I could be wrong.

Crossposting from BL. Two interesting articles on dual FAAH/MAGL inhibitors. Looks like a combination FAAH/MAGL inhibitor does the trick.

You raise a good point. I do know that in the PNAS (I think it is the PNAS paper) they mention the fact that previous single inhibitors have resulted in dead mice after just one administration after 2 days. With the new compound they have administered the drug multiple times a day over the period of 6 days and the mice did not perish. This compound also seems EXTREMELY specific to FAAH (and its small counterpart, forget the name) and MAGL and does not affect Acetylcholinesterase. Off the top of my head, the PNAS study showed after about 8-10 hours endocannabinoid levels in the test mice returned to normal with no measured side effects.

EDIT:

Thanks for the article Enkidu. Our endocannabinoid system is extremely advanced and plays a large part in our bodies. I would think that our bodies would be able to return to homeostasis once the inhibitory effects wear off. We're resilient sons of bitches    As long as the inhibitors are irreversible and don't covalently bond they seem relatively safe. Enkidu: Any worries about that Nitrogen Dioxide molecule coming off after ingestion?

Quote from: Naf1 on March 30, 2010, 04:27:54 AM

I speculated that N-(2-hydroxyethyl)acetamide in analogous doses would produce anandamide as a metabolite (in vitro).

Unfortunately, I suspect it doesn't work like that.

Although I do concede that the proposal of taking N-(2-hydroxyethyl)acetamide like paracetamol is silly, my reasoning is not! I had some references to papers that said N-(2-hydroxyethyl)acetamide was not active in the brain (google book search actually) but worked as a preservative for anandamide as the amidohydralase enzyme that hydrolyzes anandamide to ethanolamine is busy hydrolysing the N-(2-hydroxyethyl)acetamide which prolongs anandamide uptake. When looking for the paper I stumbled across this, where the exact same enzyme like most enzymes (example PAL or Tyrase) can actually preform the reverse reaction in suitable conditions  [synthase];
 
Partial Purification and Characterization of the Porcine Brain Enzyme Hydrolyzing and Synthesizing Anandamide
THE JOURNAL OF BIOLOGICAL CHEMISTRY
Natsuo Ueda, Yuko Kurahashi, Shozo Yamamoto‡, and Takashi Tokunaga
Vol. 270, No. 40, Issue of October 6, pp. 23823–23827, 1995

Abstract; Anandamide (arachidonylethanolamide) is known as an endogenous agonist for cannabinoid receptors. An amidohydrolase, which hydrolyzed anandamide, was solubilized from the microsomal fraction of porcine brain with 1% Triton X-100. The enzyme was partially purified by Phenyl-5PW hydrophobic chromatography to a specific activity of approximately 0.37 mmol/min/mg of protein at 37 °C. As assayed with 14C-labeled substrates, the apparent Km value for anandamide was 60mM, and anandamide was more active than ethanolamides of linoleic, oleic, and palmitic acids. Ceramidase and protease activities were not detected in our enzyme preparation. The purified enzyme also synthesized anandamide from free arachidonic acid in the presence of a high concentration of ethanolamine with a specific activity of about 0.16 mmol/min/mg of protein at 37 °C. On the basis of cochromatographies, pH dependence, heat inactivation, and effects of inhibitors such as arachidonyl trifluoromethyl ketone, p-chloromercuribenzoic acid, diisopropyl fluorophosphate, and phenylmethylsulfonyl fluoride, it was suggested that the anandamide amidohydrolase and synthase activities were attributable to a single enzyme protein.

http://www.jbc.org/content/270/40/23823.full.pdf+html

Previously, N-acylethanolamine amidohydrolase activity was found in various mammalian tissues (22), and the enzyme of rat liver membrane was solubilized with sodium taurodeoxycholate (21). In these works, however, the enzyme was not purified, and its reactivity with anandamide was not described. Our purified anandamide amidohydrolase catalyzed the reverse reaction and produced anandamide from arachidonic acid and ethanolamine. The synthase was also reactive with other fatty acids (palmitic acid, oleic acid, and linoleic acid) at similar reaction rates (Fig. 5B). It was reported that arachidonic acid was a better substrate for the rabbit brain anandamide synthase than palmitic, oleic, and linoleic acids, but the reactivity was assayed at a low substrate concentration (5 mM) below Km and was not compared in terms of Vmax (14). Another report showed that with bovine hippocampal P2 membrane arachidonic acid was more active than palmitic acid at 30 mM-1 mM (13). It is unknown at the present time whether or not the discrepancy of substrate specificity between these results and our finding was attributable to different animal species or different assay conditions.

22= Schmid, H.H.O., Schmid, P.C. and Natarajan, V. N-Acylated glycerophospholipids and their derivatives. Prog. Lipid Res., 29, 1-43 (1990).

Although not conclusive, my comments where not unfounded. As you can see that synthase enzyme is not only able to form anadamide but also other suitably substituted N-acylethanolamines that will bind to cannabinoid receptors the cannabinoid produced would be determined by which fatty acid the enzyme was closest too! This may not be in a massive proportion and you may well have to take a lethal dose of N-acylethanolamine before the effects of the above where actually felt, but I thought it was worth bringing up.

Crossposting again, is everyone here a member over at BL? Is it worth it to keep crossposting over here?

"The PNAS paper posted above basically explains they found that dual inhibition of FAAH/MAGL produced cannabimimetic effects due to increased levels of anandamide and 2-AG.

Earlier in this thread synapse said he had had heard of a bioassay of Methanandamide which resulted in some cannabimimetic effects but effects reached a ceiling and the substance was not worthwhile. Methanandamide is interesting; it is not hydrolyzed by FAAH effectively (if at all, not sure).

Has anyone come across a 2-AG analog that can get around MAGL like Methanandamide can get around FAAH? If so, I bet a combination of Methanandamide and the 2-AG analog resistant to MAGL would produce THC-like effects that were observed in the PNAS paper.

By the way, no one has replied to my question about the PNAS paper. Page 2 of the pdf states:

"Finally, JZL195 also inhibited rat and human FAAH and MAGL enzymes with IC50 values in the range of 10 –100 nM based on competitive ABPP assays"

Does this imply that they bioassayed the material or did they simply use a cloned human FAAH for the assay?"