• N&PD Moderators: Skorpio | thegreenhand

New evidence for cancerogenic metabolites from JWH-018

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In solution? Strange! Usually, compound are much less stable in solution than as solids... Whatever. Better not providing any sources; as you said: It won't help anyway if you're not in academia or industry.

Ahoy! - Murphy
 
Hi Murphy

I've been following this thread for a while and, after thinking a lot about it, despite my limitations in the knowledge of metabolic pathways, I strongly doubt your conclusions. It is not that I'm saying that JWH-018 is not carcinogenic. It may well be, but your argument fails for a number of reasons. I will explain my doubts pointing out two reasoning flaws I see in your assumptions:
a) The publication is the proceedings of a Toxicology conference and the authors are clearly knowledgeable in their field. The conclusion that metabolites of JWH might be carcinogenic would be much more important than the ultimate paper conclusion that "screening procedures for these drugs in urine should include not only the parent compound but also the corresponding metabolites" which might be useful from a forensic point of view, not necessarily toxicological. However, with the evidence measured, the authors chose to highlight the forensic aspects. Why? The full paper might provide clues, but apparently it is not yet available
b) The abstract is poorly written on your highlighted section. It is not clear to me what are the metabolites referenced. Perhaps you could provide your interpretation? Also do note that the JWH-015 paper mentions 22 metabolites in the in vitro conditions for the rat. These metabolites are very clearly specified but matching with the vague enumeration in the current abstract is problematic.

Also you do know the limitations of using in vitro liver microsomes, and that human liver can work quite differently than rats, so even if the study of JWH-015 was made on JWH-018, the conclusions would be very debatable.

All in all, the "smoking gun" that proves that JWH-018 is carcinogenic is still not found, nor is this forensic study a step in the right direction. Hopefully, with the media attention that this substance has, more relevant studies will appear making the matter clear. Furthermore I've been reading of people smoking absurd amounts of such substances (100s of mg per day! for a long time) and, if this substance is indeed carcinogenic or otherwise hazardous, news will very soon emerge.

R.
 
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^I'm in a hurry and will only answer in short:

With respect to a):
We shall know more when the full article about this research is published. Until then, I admit, we are relying any discussion solely on the grounds of a conference-abstract.

With respect to b):
I interpret the provided abstract as such that among the known metabolites of JWH-018, there are derivates where the hydroxylation occured in an aromatic ring system. The usual pathway towards such kind of metabolites goes via an facultative unstable epoxide-intermediate. Evidence shows (i.e. carcinogenic properties of numerous aromatic hydrocarbons) that under certain preconditions its half-life is still long enough to cause significant damage to the genome, and from a certain stage on will lead to irreversible damage. The last stage is commonly called cancer. I think that we speak at least about 10-20 years until the disease breaks out (taking "smoking cigarettes" as a widely accepted carcinogenic and popular standard). Considering the time that JWH-018 has spent now on the open market, with notable commercial success (SPICE + other smoking blends + sales of 'pure' compound). Therefore, I absolutely disagree that we will see major harm any time soon.

I think the main difference between the last statement and mine can be seen in this quotation:
All in all, the "smoking gun" that proves that JWH-018 is carcinogenic is still not found, nor is this forensic study a step in the right direction. Hopefully, with the media attention that this substance has, more relevant studies will appear making the matter clear. Furthermore I've been reading of people smoking absurd amounts of such substances (100s of mg per day! for a long time) and, if this substance is indeed carcinogenic or otherwise hazardous, news will very soon emerge.
In contrary to the last few lines, I'm of the opinion that we should not wait until we see how certain news will very soon emerge..

- Murphy
 
So, based on what I think the JWH-015 abstract is saying

NSFW:
1. Anal Bioanal Chem. 2006 Nov;386(5):1345-55. Epub 2006 Sep 6.

Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist
for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS.

Zhang Q, Ma P, Cole RB, Wang G.

Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125,
USA.

The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high
binding affinity at the peripheral cannabinoid receptor CB(2), has been studied.
A total of 22 metabolites were identified and structurally characterized. The
metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z
344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z
344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3)
dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360,
M13), resulting from a combination of monohydroxylations on both the naphthalene
and indole rings (m/z 360, M16), or a combination of monohydroxylations on the
naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation
(m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6)
N-dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7)
N-dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and
M5); 8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326,
M22); 9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).

PMID: 16955257 [PubMed - indexed for MEDLINE]



the metabloites included, on the naphthalene, only monohydroxy and contiguous dihydroxy substitutions. That's 13 possible substitutions. Are any of the epoxide intermediates demonstrably more stable (and therefore more mutagenic) than others? If so, which?

Also, regarding the benign counterexample of duloxetine, I'm guessing the naphthoxide naphthoxyl is protective, whereas the naphthoyl in the JWHs is bad news?
 
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Makes me glad I ended my trials with the commonly available JWH's for the time being...
 
I had my first experience with synthetic cannibinoids today. I smoked a Gonjah blend, and from what I read it most likely contains jwh-018 or something similar. the question of its should be of concern. I don't understand much of the bio chemistry written here, but I will share my own shamanic information. I dreamed I was eating blue strawberries(unnatural fruit), they were tasty but after a while they grew small white bulbs of plaque around them(cancer?). Despite the dreams warning I smoked anyway.
The dream parrallelled my experience. it was initially enjoyable but the after effects were cognitively disorienting and possibly cancer causing. Although I am not making any specific claims about gonjah or jwh-018, I will give my opinioin to stay away from synthetic cannibinoids. Given the wealth of plants that mother nature provides there is no reason to turn ourselves into aliens with the infinite possibilities of synthetic compounds.
 
I wrote a thread about JWH-18's carcinogenicity and the naphthalene metabolism into epoxides. I also took in account the quantity of naphthalene ingested when consuming JWH-18. It's just a theory, but it might be interesting: Thoughts on JWH-18 carcinogenicity
 
I'm surprised that with this news JWH-250 hasn't caught on.
 
its somewhat popular. most of the mentions of it i've seen have been quite glowing. It is less potent than 018 though

Hi Murphy,

It it >98% according to the technical data sheet from the supplier. It was provided as a 10mg/ml solution in methyl acetate, for stability purposes. It was obtained from a well reputed commercial chemical supplier.

The solvent was evaporated before use and replaced with acetone. I can't recall the original colour. Upon evaporation of the compound from the acetone, it was white with a very faint hint of tan.

If no one objects, I can link to the supplier. It's not really sourcing since you can't get an account for ordering purposes unless you are academia/industry

How would you know it was JWH-018 that caused your health problems? Not trying to be contrary, just curious, as I wouldn't think anyone who would smoke JWH-018 would only use that drug. Sorry you're experiencing health problems.
 
12-18 months of daily smoking of JWH-018 infused catnip caused me to develop mixed small airway disease / reactive airway disease back in October. I would use acetone as the solvent to quantatively add it to the plant materials.

My new "daily inhalation regime" consists of 2 different corticosteroids and 2 bronchodilators. Be careful.

p.s. this was all smoked using a vaporizer so the physician concensus is that it's due to the drug itself, and not smoking plant material. Be careful.
Is this the supposed source (gathered from another thread) of your health problems that you mentioned earlier in this thread?

Also, If you don't mind me asking: How much were you smoking on a daily basis? (On average, if you can even make such an estimate.)
 
Something is not clear, carcinogenicity is supposed to be induced by polycyclicring oxydation, that is one of the slower way of dégradation, several hours, days.
Almost all other way lead to more polar metabolites, that can be break in more weak places than aromatic rings, and finaly can be eliminate out of the body.
This kind of enzym compétition induce that aromatic oxydation occure mainly on chemicals that cant be destroy by other=faster way.
Its oblivious that JWH are fast acting, they can be degrade efficiantly by some fast acting enzym.
The evidence of epoxy induced metabolite in vitro is perhaps the consequence of in vitro setting.
In vivo, some metabolites discared from the system very fast, but in vitro they stay and can be attack by slower reactions.
The key point is the first JWH metabolite, if he is weak to other quick degradation, or if he can be discare fast enough, the carcinogenic reaction may not occure in vivo.
 
S
Its oblivious that JWH are fast acting, they can be degrade efficiantly by some fast acting enzym.
The evidence of epoxy induced metabolite in vitro is perhaps the consequence of in vitro setting..
perhaps it is oblivious :) good freudian slip.

I think you are confusing duration of effect with elimination and metabolic half life, THC for example has a very long half life but not a long duration of effects. The reason is that it is highly lipophillic and disappears into fat.

JWH naphthoyl indoles in humans show short plasma half life, short cns half life and absorbtion into fat, followed by slow elimination as metabolites. One of the studies shows the ring hydroxy compounds probably created from epoxides have been found in urine in humans, a urine test is never going to show the reactive epoxides themselves.

I wouldn't be too bothered provided doses were fairly low and use wasn't regular.
 
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I'm surprised that with this news JWH-250 hasn't caught on.
It is catching on, though I suspect that has more to do with state laws banning 018 and 073 than any broad awareness of the carcinogenic potential. For both reasons it's my first choice. And it's also quite nice. A high more like 018 (minus the panic attacks), though potency more like 073.
 
Does JWH-122 contain a napthalene ring? I know that isn't the end all for the potential risks but was jw. Anyway with the amount of people in the USA who would qualify as heavy synthetic cannabinoids users (usually via smoking blend products) we are gonna hav a good sample if shit does hit the fan:\
 
I have 3 grams of this stuff(jwh-018) i bought it before the law changed.. i smoked it for about a week a few years ago, but put it down only because it was so new and i had no idea if it would cause long term damage. I have been clean from pot for about 1 week and i want to stay off the pot and jwh-018 because i feel clear headed without it..

But lets say i want to get high and i dont have pot.. is it a foolish move to smoke some jwh-018? is it ok in a pinch? what do you guys think? i am not a chemist so i just dont know if its worth it or not..
 
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