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Study on JWH-018 metabolites in urine analyisis

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golden1

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http://www.ncbi.nlm.nih.gov/pubmed/20430547
Detection of JWH-018 metabolites in smoking mixture post-administration urine.
Smoking mixtures containing the cannabimimetic indoles may still be available over-the-counter in several countries. Due to the high affinity of these compounds to the cannabinoid receptors, their effective dose is lower than that of the marijuana products resulting in a low concentration of the excreted metabolites accompanied by a higher psychoactive potency. Up to now the in vivo metabolism of the cannabimimetic indoles seems to be insufficiently investigated and no data have been published on an assay of JWH-018 in urine. In this publication the urinary metabolites of JWH-018 are reported. Using gas and liquid chromatography combined with tandem mass spectrometry two main monohydroxylated metabolites were identified in the forensic urine samples. Based on the differences in their electron ionization MS/MS spectra it is supposed that one is formed by hydroxylation of the indole ring whilst the other by hydroxylation of the N-alkyl chain. The main metabolites are almost completely glucuroconjugated, whereas minor ones (N-despentyl hydroxy-, carboxy-, dihydroxy-, and reduced di- and trihydroxy metabolites) were also present in the free fraction. The parent compound was not detected in urine. (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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Can anyone tell from this abstract if the jwh-018 metabolites would contain naphthalene or some form of it that would be toxic? or does anyone have access to the full text?
 
keep in mind that if these things produce 'naked' naphtalene, this probably wouldn't show up in urine as it would go to the epoxide, and so forth, ala benzene.

i am not very knowledgeable, but i feel that you cannot use these urinary metabolite studies to rigidly exclude the possibility of jwh-018 turning into potentially harmful stuff.

edit: doh, of course then these naphtalene metabolites would show up... and they don't. well, ignore me, i'm stupid. all these designer cannabinoids kinda scare me...
 
awesome stuff, glad you found the study:
jwh-018-metabolites.png
 
Uh-oh, the M8-M11 metabolites don't look so good. I'm guessing they form via an epoxide intermediate?

graphic11.png
 
mpomk said:
"Uh oh" in what sense?
Click to expand...
as in these metabolites are created from reactive epoxides essentially by reaction with water, these same epoxides will react with other things as well if they can, and these things include DNA and other vital cellular components, if the thing is greasy and sticks around rather than being excreted easily the chance of cellular mayhem is greater. The carcinogenic polycyclic aromatic hydrocarbons are dangerous for precisely this reason, the body can't easily get rid of them and they are metabolised to reactive compounds (the actual carcinogenic compounds) and these reactive compounds are pretty good at reacting with DNA or just sitting in between the DNA causing misreading of the DNA, either way they are not good news.
 
Given that none of these metabolites are epoxides in and of themselves (and issues with lipophilicity aside) is there some reason that the epoxides would not be excreted even in the most minute quantities - and is expoidation the only possible route to the dihydronaphthalene metabolites in M8-M11?
 
Many thanks for the explanation. While it certainly sounds scary (and obviously I am a user of synthetics, so I obviously have a personal concern, though I primarily stay with 250 and 081 rather than 018 in raw form), is there any way to gauge risk from this new information? I would assume that as of yet there is not sufficient information to allow us to put even a ballpark figure out for a question like "how likely is this to cause me to develop a cancer," but can this study help place risk somewhere along a scale ranging from "no risk" to "almost certainly"?

Rather, does this new information give sufficient data to say whether 018 is a product that represents a theoretical risk for heavy users, or to say on the other end that 018 is cranking out highly cancerous nasties in such a large quantity that it's a massive cancer risk on that fact alone?
 
I have the same doubts... Can We almost be certain that even light users (aka once per week normal dose users) will have a moderate/high chance to develop something very nasty like some form of cancer?
I mean...For example: If one person smokes a packet of cigarrettes only on saturdays...obviously he actually IS CONSUMING a cancerigen substance...but its considered a normal and even acceptable risk. Could this be applied to JWHs too? And WHAT ABOUT CP 47.497?
 
the risk has not been determined,
There is reason to believe a risk exists because the metabolism studies indicate that lipophilic epoxides are involved as metabolites. that is as far as it goes, it may be that these metabolites are not carcinogenic equally they may be, and people need to accept that these compounds are research compounds with next to no real data and not expect there to be answers. If anything the presence of potentially damaging metabolites a very good reason for moderation of consumption of napthoyl indoles.

even with things that are known carcinogens the individual risk of cancer is difficult to determine and people generally have difficulty working out the risks they are willing to take, the most sensible thing is to reduce exposure to all carcinogens to as low a level as possible.

What would be required is an epidemiological study over the next 20 years, which is a bit late the exposed population has only been exposed for 4-5 years at most and it would be surprising if they were showing any differences at this point.

So expecting someone to compare the risks to smoking cigarettes is wrong, nobody has the data and nobody has the answer.
 
Wow!!! That was what I call a really good educated, concious and measured answer to my question. I think you're right, you take out all the "desires" off...(the desires of JWH NOT being sooooo possibly bad for the consumer's health).
Maybe someone like me...liked to think that smoking JWH in low doses, only once per week for pure relax and recreation...were almost the same to smoke a packet of cigarrettes on weekends...
I was an avid smoker two and half years ago...and I quit.
Now I think, that it's time to reconsider stop with the "once per week JWH consumption" too. That's too bad...but maybe I wasnt the only one with that kind of hopes...
Again, thanks Vecktor.
 
vecktor said:
as in these metabolites are created from reactive epoxides essentially by reaction with water, these same epoxides will react with other things as well if they can
Click to expand...

Would the presence of the indole part of the structure reduce this risk though, seeing as the metabolism doesn't produce any free naphthalene? From looking at the most carcinogenic PAH compounds they all seem to be just a bunch of fused benzene rings with nothing else attached to them.
 
I sincerely do not understand this "witch hunt" against JWH compounds. Just because a compound is a research chemical it does not make it more dangerous than a natural compound. As far as I can see, there are no reason whatsoever for alarm. Naphthalenes and epoxides are natural compounds and some of them are demonstrated anticarcinogenic. Sure, JWH-018 may form epoxides, but even if it does, it is a long stretch to point to a "smoking gun". Even pure naphthalene is only very moderately carcinogenic, if at all. If you keep mothballs in your house, you have most probably inhaled a much larger amount of naphthalene than smoking some mgs of JWH-018 over the weekend
 
Alright, so I'm not at all an expert in chemistry, in fact my knowledge of it is VERY VERY limited. But, I am a good researcher.

It seems to me that the metabolites M8-M11 on the naphthalene end of the molecule are the same thing as one of the metabolites for naphthalene,
trans-1,2-dihydro-1,2-naphthalenediol. Google it and you'll see that they're the same.

Source:
http://www.ncbi.nlm.nih.gov/pubmed/16243959



All of what I'm saying could be complete bull, however. Any insight from someone with some knowledge?
 
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