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[MEGA] JWH-018 Thread

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Then my answer is YES: Appetite is suggested to get triggered via CB1 (plz somebody correct me if I'm wrong) and as long as a substance is a sufficiently potent agonist there, you will get hungry like hell... 'Experimentally' confirmed for weed and JWH-018 as well. ;)
 
Half-life "appears" quite shorter than Duloxetin etc.,but this is subjective judgement.Once smoked 10mg JWH-081 (pentyl,with a methoxi) and while "quite uncomfortable",it was over within an hour mostly.The reason I make this point,the alkyl-indole is slightly basic which could lower logP and increase excretion.
 
MurphyClox said:
I have to be pedantic and request to get cited accurately: I always used the terms "possibly", "presumably" and alike in combination with "cancer" or "cancerogenic".
Click to expand...
He talked about your "theory", and a theory is always based on assumptions. So this is no inaccurate quote of yours.

Besides, and in this point I am in complete agreement with you, Murphy, Mouse could not really improve his credibility with his latest posting... he has not provided any informative basis yet.
 
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Carcinogens not necessarily carcinogenic

Here is something encouraging referring to the whole issue about carcinogenicity that accounts for the strange title of my post:

"In fact, our food contains not only a few, but probably thousands of chemicals which could produce cancer in animal studies. Therefore it makes little sense to complain about every new discovered natural material for which there are toxicologic animal studies plus a sensitive verification procedure. The crucial question rather is, if there is a epidemiological correlation between a certain aliment and the development of cancer."

Source: http://www.tagesspiegel.de/meinung/kommentare/Krebsausloeser-Acrylamid-Glycidamid;art141,2596976 (german)

OK, the thing with the sensitive verification procedure, which refers to the possibility of detecting even the tiniest amounts of a chemical, is not really appliable on JWH-018, which is suspected to produce comparatively high amounts of possibly carcinogenic substances (via metabolism) due to its high amount (milligrams) in Spice.

But there is another interesting information which is concerning the thing with the epidemiological correlation and is namely about glycidamide, the primary epoxide metabolite of acrylamide and the likely cause of the carcinogenic effects of acrylamide observed in animal studies:

While the concentrations of glycidamide found in food are (with 0,3 - 1,5 microgramm pro kilogramm) about 1000 times less than the ones of acrylamide itself, it is in any case produced in much higher concentrations via the metabolization of acrylamide in the lever.

However, there seems to be no interrelation between the consumption of both acrylamide and glycidamide and the most common forms of cancer. There is no single statistic correlation, not even at factory workers who have been exposed to high doses of acrylamide over years.
 
Vektor you are making some incorrect assumptions.

We have nothing to do with the idiot RC venders and commercial JWH-018. I agree with you about the ungodly purity of the JWH-018 that is being circulated along with the false purity claims from the RC company are quite revolting.

I did not claim to have tested pyrolysed, inhalation route, etc... Answer is No. As far as I know, those issues remain yet to be further defined.

If we intended to name the lab that did the tox work I would not be posting here anonymously.

I'm travelling half way around the world at the moment, and I don't have access to my files. The reason I posted first without having details in hand was Murphy said he was preparing his report about the epoxide and other issues and I wanted provide some alternative perspective and discussion before that article went to print. He has posted it already anyway, so the jwh causes cancer story will likely circulate to the media regardless. You can be sure the media will fail to mention the words "possibly" and "presumed".

Murphy I'm glad to hear your open and willing to adjust your report as further data comes in.

I have nothing to prove here, simply wish to bring some very interesting data to the table. OK I will just shut up now and return when I have the report.

Adios and Merry Xmas!
 
hugo24: Yeah it's an interesting point huh, the short duration of effect. As for as non-epoxide metabolites go (so, we avoid the aromatic rings), i'd have thought N-alkyl chain terminal hydroxylation and N-dealkylation to be the most probable. Both these metabolites should be inactive (or much less active, anyway), satisfying the short duration. The former metabolite has a log P of 3.78 and the latter, 4.48. Still somewhat high but not too bad. So I guess the question is, would these be eliminated quickly enough that further metabolism on the aromatic rings (leading to epoxide pathways) isn't required or constitutes only a tiny fraction of the ingested dose ?
 
anonymouse99 said:
Vektor you are making some incorrect assumptions.

If we intended to name the lab that did the tox work I would not be posting here anonymously.

I have nothing to prove here, simply wish to bring some very interesting data to the table. OK I will just shut up now and return when I have the report.

Adios and Merry Xmas!
Click to expand...

no. I have been careful with my wording not to suggest any link with the commercial vendors or the chinese company(s) that is making this.

My personal gut feeling is that JWH 018 is safe and the epoxidation is a red herring, I have said as much previously. however I have concerns about the safety of impure material and the safety of smoking any of these materials. but I have no solid data at present.

I await your report with interest.

A thought for the day :

The cameleon be better camouflaged if it were transparent
 
Real world use

For a change we have empirical "evidence" as opposed to the usual theoretical or modeling. As was pointed out, Spice has been using JWH-018 for a while and I know of one product that has been on the market for a year or so that contains it with thousands of packets per week going out, and many customers using daily/weekly for that whole time. The lab that makes the 018 has two people there that have been evening smokers of the product nearly every day for 15-18 months.
While I appreciate that none of these folk were given full medicals before they began, nor was their lifestyle/demographic detail tab'd, but to the best of my knowledge no one has developed anything either.
Remember, depending on what software you use THC is a potential carcinogen with some metabolites that should worry observers too.
Cancer appears to be a package, with the triggers being different from one to another which might help explain the myriad irresponsible bastards that seem to do whatever they like and have little/no health issues, while we all know of the poor sod who seemed to lead a blameless, macrobiotic, Ironnman lifestyle and died of brain cancer at 36. As a practical geneticist once said "If you want a long and healthy life, pick your parents".
I'm not advocating anything, just making the observation that a manufacturer that uses this compound regularly visits a major outlet and talks to employees and customers to get any feedback he can, and has to date not heard of a single case of any illness or condition that has persisted in over the year of sale, and while this is hardly a peer reviewed, control study, it has to be of more legitimacy than any modeling, and as I can't see any organisation conducting long term studies using this or similar compounds, I would guess it's the best/only you'll hear of.:D
 
I don't know that I agree. While at this point there is no good evidence, what you present certainly doesn't disqualify it as a potential carcinogen. Would you have health problems from smoking cigarettes for that time period? No, so why use their absence as any sort of disqualifying evidence for JWH-018??

I agree with Vecktor- it probably will turn out to be a red herring, but people need to be educated in the mean time. With the looming criminalization, it will researched heavily in the years to come.
 
I made an additional cancer risk analysis on JHW-018 that is sold as fertilizer [in German], under the assumptions that
1. Naphtalene is the most harmful substance found therein
2. The purity grade of this "fertilizer" is truly 98% as indicated

I am not that well educated within biochemistry/pharmacology/etc., but do this more as a sort of hobby. Therefor I'd really appreciate it if you would take the time to read my argumentation, critizice it and punch holes into it :)
I would also link to eventual answers from here myself there.

I know that my post here is practically useless for all non-German speakers here. I did a very fast translation into English, so please don't blame me for the language...

1. The named JWH-018 fertilizer product is not very clean, or else it would be more colorless. The indicated purity is 98%

2. The assumed metabolite Naphtalene seems to have a carcinogenic potential.
According to the IARC-Monograph
The maximal rates of metabolism measured in human lung microsomes are about 10–100 times lower than those in mice.
[...]
There is inadequate evidence in humans for the carcinogenicity of naphthalene.
There is sufficient evidence in experimental animals for the carcinogenicity of naphthalene.
[...]
Naphthalene is possibly carcinogenic to humans (Group 2B).
Click to expand...

2B ist the same cancer group as ethanal, a primar metabolite of ethanol.

About the carcinogenicity of naphtalene, there are 2 interesting in-vivo studies on animals.
A) Rats were applied per oral a dose of 110mg/kg naphtalene. After 15 days there were no carcinogenic activities found yet, but after 30 days and more there were increasing DNA fragmentations (an indicator for cell death or cancer activity) in liver and brain.
B) Mices that were applied per oral 1100 mg/kg naphtalene showed DNA fragmentation within their brains. Mices with a genetical defect [p53 deficient] the effect already occured at 110mg/kg.

Additionaly there are indicators that naphtalene might cause hemolytic anemia, which we leave aside for the moment.

3. The synthesis of JWH-018 should - according to MurphyClox - not need naphtalene and it is also unlikely that the synthesis causes to produce naphtalene as a by-product. Unfortunately I don't have access to any syntheses studies of JWH-018 right now to make a further risk analysis on those educts, but I assume that if there was more carcinogenic substance involved in the usual synthesis, MurphyClox would have mentioned that one.

But let's assume that the known "fertilizer" consists of 98% JWH-018 which is fully metabolized into naphtalene and that the remaining 2% are naphtalene (which is already unlikely, because naphtalene is colorless as well).
This would yield 0.02mg pure naphtalene and 0.375mg naphtalene metabolites = 0.395mg naphtalene.
Let's say, that naphtalene is more than 5 times more carcinogenic on humans than on mices without p53 deficiency [in my sense quite unlikely]; so 200 mg/kg are already carcinogenic. For a light human of 50kg it would take 10g of naphtalene or 25.3g fertilizer (which is about 2500 strong dosages of 10mg; usual dosages should be within 1-3mg).

The smoke of a cigarette should create about 0.422µg of naphtalene. Taking only this into consideration the fertilizer would be extremely toxic, as this would be about 937 cigarettes for 1mg of fertilizer [but cigarettes create of course a lot of other harmful substances].

We might also make a comparison on ethanal - the primar metabolite of ethanol - , that also falls within the 2B cancer scale. For mices an ip injection of 0.4µg ethanal was associated with cancer cell activity [Sister chromatid exchange in the bone marrow].
The following comparison is in some way flawed, as the cancer activity for ethanal and naphtalene were measured in different areas with different methods and the metabolist time of both substances may also differ, but I'll do it anyway. A mice might have at least a weight of 40g = 0.04kg ; let's assume we had there 10µg/kg ethanal. Because ethanal and ethanol have almost the same molar mass, this would be about 10µg/kg metabolisized ethanol. Let's assume that the cancer activity on humans is 100 times less likely, so to start at about 1mg/kg and further that only 50% of ethanol per oral is metabolized. So if a human would drink about 2 litres of beer at 5% alcohol, he would have already metabolized 50mg of ethanal; so our 50kg human would have already reached the cancer risk level!

This leads my to the following conclusions
The impurity doesn't actually result in much more higher naphtalene level (5% at maximum), given that the purity level of 98% is correct.

The cancer risk - given that naphtalene ist the most harmful metabolite that might arise from the fertilizer - is small, compared to alcohol.

The risk of a hemolitic anemia, has to be further investigated.
Click to expand...
 
ethanal = acetaldehyde for those who don't realize this (I didn't).

All of this calculation is useless though. I don't think napthalene is a metabolite, however, we know that at least part of JWH-018, in rodents, will likely be metabolized to epoxide intermediaries. I don't think anyone is saying free naphthalene will result, but rather these epoxide intermediary metabolites that are formed will be rather dangerous.

None of that has any meaning unfortunately. JWH-018 expoxide metabolites could be 1000x more dangerous than free naphthalene. Or it could be .5x as dangerous, who knows.

Then we should consider whatever the 2% garbage is (or 35%+ garbage in one vendors product!!), its dangers, the metabolites and pyrrolisis products (and their metabolites!!). Then you need to consider the pyrolisis products of JWH-018 itself, and their metabolites.

And you think that this has absolutely any meaning? You haven't even begun to scratch the surface.

The only one of your conclusions that makes any sense is the final one, since who knows if the claimed impurity level of 98% is accurate (because from at least one vendor, it's absolutely a lie!), and naphthalene may be much higher (if as a result of pyrolsis). And who could possibly say that naphthalene is the most dangerous impurity or metabolite? No one, since even the (what I suspect is a hoax) claiming to have run real somewhat valid screenings didn't look at the most likely source of carcinogens- the shit that results from burning 018.
 
Thank you for the fast reply.

we know that at least part of JWH-018, in rodents, will likely be metabolized to epoxide intermediaries
Click to expand...
Could you tell me where to find those results? I only knew the JWH-015 paper by Zhang et al., which does not list any epoxide intermediaries AFAIK.

I almost guessed that the 98% purity claim is questionable, according to that photo I saw.
Could you tell me where the 35%+ garbage result comes from?

I know that my "analysis" has very narrow assumptions. I also stated those clearly.

Of course you are right about burning JWH-018; I actually didn't take that into consideration as I regard smoking anything as way more harmful than takit it per oral [and hardly smoke anything myself].
 
JwH-018

I'm not a member here but here is a COA for one company's JWH-018. This is not from the new (Dec 4) and well known vendor, but from another Chinese company. The company info has been blurred for obvious reasons. It was posted somewhere else and reposted here. The COA describes it as an orange oil solid, not an off-white powder. This isn't conclusive (I know the well known vendor could have bought from this company etc etc), but it's the ONLY document I've seen referring to its appearance. Take it for what you will. :)

http://i42.tinypic.com/k51ock.jpg

About the metabolites etc... Here is what Hoffman had to say on the subject:

Mr. Markuse,
I can only supply limited answers to your questions. We have never investigated the long term effects of JWH-018 in animals and other than the anecdotal data from Der Spiegel and assorted blogs that my wife unearthed there are no data regarding its effects in humans. In mice it is considerably more potent than THC as we published almost ten years ago. I don’t have any idea regarding the safety or toxicity of this compound nor any information regarding its bioavailablity. THC is also a CB2 agonist, although with less affinity for the CB2 receptor than JWH-018. I have no idea if 018 is a CB2 agonist or inverse agonist/antagonist. I would note that we have made over 100 cannabimimetic indoles in the last 15 years and jWH-018 is just one of them.
I hope that I have answered your questions satisfactorily.
Regards,

John W. Huffman
Research Professor of Chemistry
Clemson University

Update:
"Please emphasize that there are no toxicology data for this compound."

REF:http://www.pierre-markuse.de/2008/12/16/spice-jwh-018-email-von-prof-john-w-huffman/

I do not know the legitimacy of this blog and I cannot read German. If it is really him, it seems odd he wouldn't at least mention epoxides, naphthalene etc as a possibility, if it is so easy to determine from the structure. :/ Perhaps if someone asked him directly?

About the well known vendor: He/she seems a bit sketchy for not providing the documents upon request. Another company was emailed and they provided a PDF within 24 hours. The prices will not be very good either without the 2 for 1 deal.

You can put this in any of the JWH-018 threads that talk about its appearance. Here's one:

http://www.bluelight.ru/vb/showthread.php?t=407913
Thread Title: "Jwh-018"

Thanks!
 
PURE JWH-018 should be a white crystaline solid. Now, that never happens.

It should be light yellow to yellow. Orange would have me worried (an orange oil???)

Considering the reliability of chinese everthing else lately (melamine anyone?), I wouldn't be surprised if more than 50% of these things are forged.
 
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