Ok, so you smoke 15 mg of JWH-018 in a night. Or, say, 30 mg of 073. That means that you have >15 or >30 mg respectively of metabolites floating around, right? Is that enough carcinogen to give you cancer, significantly increase risk of cancer, or fuck you up in any other way? How about if you smoke the aforementioned doses of JWHs twice a week for a year? that's close to the moderate pot smoker's yearly # of days of smokage...
Nobody (absolutely NOBODY) can say after which dose you will have a x% higher risk of getting cancer. In theory one single molecule is enough to cause the harm. Of course, that's just theory. The most practical and realistic approach to cancerogenic substances is to avoid contact
at all, or as much as possible.
you hack most of the glue out anyways the morning after in one or two big ole loogies...so I doubt you end up keeping most of it in you anyways...
UHHH!!! Bad misconception. Even if only minute amounts stay in your respiratory ways (and it's probably more than just "minute") that would be enough to cause
major trouble. Cancerogenics acts in the long-term and are usually applied chronically and in low doses. Best known example, albeit not the only one: Cigarettes!
I think it's nonsense to claim that naphthaleneyl containing groups are carcinogenic due to some epoxide formed metabolically. Just look at duloxetine (
http://en.wikipedia.org/wiki/Duloxetine) which contains the same naphthalenyl group as JHW-18 and is used as a medication for humans. Duloxetine would't have gotten that far if there was any indication that it's carcinogenic. Saying that JHW-18 is carcinogenic due its naphthalenyl moiety is just bullshit.
Very bad
misconception, too, IMO. In short, some reasons:
1. While it is allowed to compare JWH-015 (for which the toxicology study was made) with JWH-018 (which is the most prevalent AAI) due to the
very close structural relationship, one cannot easily compare unrelated structures.
It depends for example on the orientation of the molecule in the CYP-enzyme, with causes the epoxide-intermediates. For a first idea (i.e. low reliability but at least an info), one could try a virtual docking of the substance in the relevant CYP-structure; if the naphthalene gets close to the active center, it will probably get metabolised, too. This is not trivial!! The sheer presence of a naphthalene-moiety doesn't automatically mean that this is a site for metabolism. Again: JWH-018 and 015 ARE
comparable and for 015 the cancerogenic metabolites were shown to be within the possibilities.
2. JWH-018 offers only very few possibilities to get metabolize at all, same to 015 and lots of other AAIs, too. This makes even less probable metabolism pathways an issue again. Now add the high lipophilicity of the compound. Combine both facts and I would vote for quite a long biological halflife
in vivo (...without having seen a respective study). The stuff stays in your damn fat tissue and has a LOT of time to perform even the most improbable metabolic pathways.
In Duloxetine I can see instantly
several possibilities to transform the molecule into an easily excretable metabolite. Wiki says "Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours)", although I dunno where this info was taken from.
The statement that this particular compound (and closely related congeners) is
presumably (but of course not "certainly") cancerogenic in humans is absolutely justified!
Peace!
Murphy