• N&PD Moderators: Skorpio | thegreenhand

New evidence for cancerogenic metabolites from JWH-018

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I don't know that that's true about immune suppression necessarily causing increased cancer.
epidemiological studies would suggest otherwise. The link between immunosuppression for organ transplant cases and increased cancer risk has been recognized for quite some time. whether it is important in the possible activity of JWH compounds who knows, the combination of a immunosupressant that can trigger immune cell death along with the possibility of the same compound producing carcinogenic metabolites could be really bad or it could amount to nothing.
so far this just highlights the difficulty in making any predictions with respect to JWH compounds, the cannabinoids which we have data for are the benzopyran compounds THC and similar and there is minimal data for the JWH compounds, full stop.

until the data becomes available then all we have is pretty pointless speculation, no amount of literature and google searching will find the answer because simply the answer is not there at the moment.

fwiw - probably best to forget the EPA article as EPA is not just some immuno active compound but has many other effects.
 
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So does this undermine the credibility of the 'anonymous' GreenScreen HC Genotoxicity Assay that was supposedly carried out on JWH-018 recently,
Seeing as the findings showed that it didn't cause any damage to DNA in liver cells?
I've noticed since this study has been posted on here, the previous anonymous report has been un-sticked from another well known drug based forum, perhaps in light of this recent evidence?
Are people once again starting to question whether or not it was indeed truthful?

And if we are still to take the Genotox findings as valid, would that mean that despite this route of metabolism, there still isn't a cancer threat, as is the case with duloxetine which Nuke pointed out?
Would this be a good enough reason for it to come back negative on the genotoxicity result, or is there something afoot?
 
I think that this was answered best in Vecktor's last post. I quote:
until the data becomes available then all we have is pretty pointless speculation, no amount of literature and google searching will find the answer because simply the answer is not there at the moment.
And that's it.

- Murphy
 
Forthe record, at least in the United States, Thalidomide is still available, but only for multiple myeloma, I think.
 
...yeah, it is still available for some highly limited indications. I cited this example more in the general context...
 
I think that this was answered best in Vecktor's last post. I quote:

And that's it.

- Murphy

I see... If that's the case then why not just present the data as it stands, without attaching "pretty pointless speculation" on the end of it, along with the thread title?

It seems as though it's OK to post speculation for carcinogenic potential, but not against.
If one were to read into this, they might come to the conclusion that this thread is more about clearings ones name, than it is about the potential harms of JWH-018.
 
I see... If that's the case then why not just present the data as it stands, without attaching "pretty pointless speculation" on the end of it, along with the thread title?

It seems as though it's OK to post speculation for carcinogenic potential, but not against.
If one were to read into this, they might come to the conclusion that this thread is more about clearings ones name, than it is about the potential harms of JWH-018.

please feel free to summarize the available (solid) data on jwh-018 and post it here, I think it will end up being a rather short post.

Scientifically I take no position either way, I have not seen any convincing evidence one way or the other, if the tox study was published in the peer reviewed literature rather than anonymously online I would attach much more weight to it, because I suspect the people behind it are dodgy. I
this is not my field. I know relatively little about it however I think that GreenScreen HC is designed for limited early stage testing of NCE's to get a general idea as it looks for just one gene associated with DNA damage.
It would be much stronger seeing a series of tests on the metabolites giving JWH the all clear. there are a couple other things in the "anonymouse" toxicity study that raised a couple of eyebrows.

for what it is worth I personally have tasted quite a few JWH compounds a couple of years ago, but in strict moderation. they are interesting but I don't think they are all that great, and I still prefer cannabis when I feel the need to agonise CB-1 CB-2 arises (which is not often).
 
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please feel free to summarize the available (solid) data on jwh-018 and post it here, I think it will end up being a rather short post.

Scientifically I take no position either way, I have not seen any convincing evidence one way or the other, if the tox study was published in the peer reviewed literature rather than anonymously online I would attach much more weight to it, because I suspect the people behind it are dodgy. I
this is not my field. I know relatively little about it however I think that GreenScreen HC is designed for limited early stage testing of NCE's to get a general idea as it looks for just one gene associated with DNA damage.
It would be much stronger seeing a series of tests on the metabolites giving JWH the all clear. there are a couple other things in the "anonymouse" toxicity study that raised a couple of eyebrows.

for what it is worth I personally have tasted quite a few JWH compounds a couple of years ago, but in strict moderation. they are interesting but I don't think they are all that great, and I still prefer cannabis when I feel the need to agonise CB-1 CB-2 arises (which is not often).

Interesting, I was under the impression that the results were considered genuine by quite a few people in this field of expertise, although because of the rather strange way in which it surfaced, no one wanted to put the official stamp of approval on it.
I too have a very limited knowledge in this area, and didn't realise the results had raised a few eyebrows.
Forgive me if I was pointing the finger slightly, but this whole 'is it, isn't it carcinogenic?' debate is the kind of thing that anti drug heads love to use a long time after the question has reached an official answer, and even if it's cleared in the future, the image of the substance is left tainted.
While I appreciate people wanting to raise their concerns, what with the recent article in a certain magazine publication, many people are already under the impression that JWH-018 is raw malignant tumour in the form of powder. 8)
 
While I appreciate people wanting to raise their concerns, what with the recent article in a certain magazine publication, many people are already under the impression that JWH-018 is raw malignant tumour in the form of powder. 8)

Whoever those "many people" are - they must be illiterate!

Nobody, at least nobody with the appropriate scientific background and honesty, ever said something about a definite cancerogenic activity of those compounds. It was always said that this was just a preliminary assumption, based on indeed just little information available.

Personally speaking, it was always my point that there were several indicators pointing towards the potential harmful sideeffects of these compounds, especially in the long term. I couldn't see any indicators pointing toward the benignity of said compounds. The rest is basic math.

As long was don't see further toxicology studies, further discussion is pointless. The aim of this thread was fulfilled with the very first post: To present the most up-to-date toxicological information about some of the most popular (semi)legal synthetic cannabinoids. The rest is up to everyone on his own.

:\

- Murphy
 
Would it be a reasonable idea to ask those guys "burning hundreds of mg a week" to have a health check and come back with results?
 
Personally speaking, it was always my point that there were several indicators pointing towards the potential harmful sideeffects of these compounds, especially in the long term. I couldn't see any indicators pointing toward the benignity of said compounds. The rest is basic math.

When we're saying carcinogenic here, is this more specific than mutagenic?

I'm comfortable assuming the epoxides in question would be mutagens if exposed to DNA, but is it known that they all target reproductive functions? I seem to remember the benzopyrene diol-epoxide specifically targeting some gene responsible for cell death, and that's what made it carcinogenic.

That's my understanding, at least. Isn't the damage of DNA functions that regulate cell death and reproduction what makes something carcinogenic?

Not that I'm downplaying the randomness of ingesting mutagens, I'm just curious if there's specific knowledge that the naphthalene epoxides in question are proven carcinogens.
 
Just to put this into perspective, and I hope I'm not trying to simplify this too much:

How bad is JWH-018 compared to other known carcinogens.

Is this closer to the carcinogenicity of tobacco smoke? or are we talking on par with mesothelioma?

less? more? It would help to know what type of risk one is putting themselves in, as opposed to just knowing that there is a risk.

^^^?
 
It's hard to tell, since you don't really know what you're getting when you combust your material.

Tobacco smoke generally has about 60mcg of benzene and 30ng of BaP per cigarette. JWH-018 smoke, at a 5mg dose, contains about 1.9mg of naphthalene.

The main mechanism by which straight naphthalene is carcinogenic is similar to benzene where the 1,2-Dihydroxy compound is first formed followed by the transformation to the 1,2-Dione compound, which then covalently bonds to DNA. This is largely dependent on the compound being a substrate for a number of CYP ***s and aryl hydrocarbon hydroxylase.

So the dangerous parts of the metabolism in rats boils down to diohydroxylation of either the arene group on the indole or the naphthalene -- both of which were shown in the study. Both of these can likely covalently bond with DNA. On comparison by weight there's a lot more compared to say, benzene in cigarettes, but the reality is we won't know until a bunch of toxicity studies are conducted. The worst part is that carcinogenicity is insidious: you may be fine now, but 10 or 20 years down the road you might develop lung cancer.

Would it be a reasonable idea to ask those guys "burning hundreds of mg a week" to have a health check and come back with results?
No, because the doctors won't be able to see where metabolized molecules of JWH-*** are binding to their patients DNA irreversibly.
 
It's hard to tell, since you don't really know what you're getting when you combust your material.

Tobacco smoke generally has about 60mcg of benzene and 30ng of BaP per cigarette. JWH-018 smoke, at a 5mg dose, contains about 1.9mg of naphthalene.

The main mechanism by which straight naphthalene is carcinogenic is similar to benzene where the 1,2-Dihydroxy compound is first formed followed by the transformation to the 1,2-Dione compound, which then covalently bonds to DNA. This is largely dependent on the compound being a substrate for a number of CYP ***s and aryl hydrocarbon hydroxylase.

So the dangerous parts of the metabolism in rats boils down to diohydroxylation of either the arene group on the indole or the naphthalene -- both of which were shown in the study. Both of these can likely covalently bond with DNA. On comparison by weight there's a lot more compared to say, benzene in cigarettes, but the reality is we won't know until a bunch of toxicity studies are conducted. The worst part is that carcinogenicity is insidious: you may be fine now, but 10 or 20 years down the road you might develop lung cancer.


No, because the doctors won't be able to see where metabolized molecules of JWH-*** are binding to their patients DNA irreversibly.

But, the carcingenicity of cigarettes is not due to the small amount of benzene in the smoke. It is due to things like N-nitroso-nornicotine, which can react directly with DNA without further metabolism. So this is comparing apples and pineapples. ;)
 
This is true, there are lots of other compounds and radioactivity to consider as well. The amount of benzene though is not insignificant, same with BaP, when you use these things daily for a lifetime the damage to your genetic material accumulates.
 
i would be more worried about environmental factors such as radon. yummy ionizing radiation! its the largest contributor to a persons background radiation dose. #2 in causing lung cancer and god knows what else.

smoking anything is bad since it has synergistic effect with radon decay chain products along with shit that gets created in the combustion. radon progenies can easily attach to smoke / dust and hence lodge in the lungs. half life of some progenies is short but they do nice damage overtime. the decay chain leads to some nice ones such as 210Pb with halflife of 20+ years (1/20000 activity compared to radon tho). if you are vaporizing jwh-018 properly this effect is null.


The metabolites from even large use would shy and crawl into a ball and die in comparison to anything smoked, specially indoors.


But its good to know that more research work is being done on jwh-018. Hopefully soon we will get some data about which enzymes are responsible for metabolizing it in humans so people can assess the harm potential properly plus check if it could mess with any meds they are on. But it does sound weird since i remember reading some company working on a jwh-018 transdermal patch in some EU country.

Right now this evidence doesn't really bring anything to the table really and i agree with 33hz. I got the exact same feeling when reading this.
 
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kken;8129189 if you are vaporizing jwh-018 properly this effect is null. .[/QUOTE said:
how does that work? vaporising the material still makes finely divided particles that enter the lungs and according to your theory would hoover radon daughter products out of the plasterboard walls. It is not as if vaporising these kind of things results in inhalation of vapour, instead it is merely a way of making very finely divided droplets very similar to smoke..
The difference could be argued along the lines that vaporising leads to less decomposition products than smoking because of the lower and more precise temperature control.

Some day someone will look at the pyrolysis products of JWH 018. Pyrolysis of naphthyl ketones is a standard way of synthesizing some very unpleasant polycyclic aromatic compounds,, many of which are potently carcinogenic.

It is very unfortunate the fuckers made the stuff illegal making research so much more difficult.

Until then the jury is out.
 
Kken, interesting your radon mention. The adverage joe receives around 500mR/yr. 200 of that is directly due to radon, the half-life is very short tho, at most 4 days, but usually around 8 hours.I have seen radon attach itself to many things (even static feilds) but I don't think people should be worried about it. I receive around 5000mR a year, but cancer is no more prevalent in my profession than in any other.
 
so question, and forgive me if my understanding is poor:
Couldn't some JWH be vaporized in a cold finger apparatus, and then the residue collected and analyzed to find possible combustion by-products?

Isn't the risk here more concerned with the metabolite(s) of the drug and not the actual drug itself?
 
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so question, and forgive me if my understanding is poor:
Couldn't some JWH be vaporized in a cold finger apparatus, and then the residue collected and analyzed to find possible combustion by-products?

Isn't the risk here more concerned with the metabolite(s) of the drug and not the actual drug itself?

indeed it could, by a lab with the appropriate licence, GC-MS and the inclination.
 
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