I'm pretty sure they did a screen (I think it is called a "Green Screen" that showed the JWH-xxx's to not be carcinogenic).
JWH-018 Toxicology
Saturday, February 21st, 2009 | Author: Synchronium
Since my last post about the spice behind Spice, it has been brought to my attention that some initial toxicology testing has been done on the synthetic cannabinoid JWH-018. Before we get down to the details however, here’s some pretty weird background information – the sponsor and provider of these studies wishes to remain anonymous! Unfortunately, this makes the whole thing a lot less credible, but since this is the only information we have right now, let’s hope someone else can verify these things at a later date. So far, one professor (who also wishes to remain anonymous) thinks these are real, but as of yet, no one is willing to put their name down on any kind of formal statement. If you, or anyone you know, has the relevant expertise to look over these studies, please drop me a line!
Feel free to invent your own conspiracy theories, but for now, let’s take a look at the data. You can download the PDF documents in this Zip file [2.04 MB]
CYP450 Inhibition Assay
This first assay looks at the effect of a drug on specific enzymes in your liver. These Cytochrome P450 enzymes are responsible for metabolising the vast majority of drugs you might put in your body, so if you’ve got too much of one drug in your system (ie paracetamol/acetaminophen), then other drugs that are also metabolised by these enzymes (ie alcohol) may compete for these enzymes and so hang around in your system for longer. As you can imagine, it’s important to understand how one drug may affect the metabolism of another, in case of any disasterous drug-drug interactions.
Results: JWH-018 will probably interact with the metabolism of other drugs, so more in vivo work is necessary.
hERG Binding Assay
hERG stands for human Ether-à-go-go Related Gene. This gene codes for a particular type of potassium channel found on heart tissue. This channel pumps potassium ions out of the heart muscle cells and are critical in coordinating the heart’s electrical activity. Unfortunately, these channels are a prime target for drugs to bind to, disrupting their function. This can lead to “Long QT Syndrome”, associated with fainting and can lead to sudden death, so you can see why these kinds of tests are important. Here’s a typical ECG recording showing what’s called the “QT interval” shown in blue, which lasts for longer than it should do if these channels are disrupted.
Results: JWH-018 does not interfere with these channels. That’s a good thing.
Cytotoxicity Assay
This simple test essentially looks at how many cells die when you perfuse them with a drug. The more cells that die, the more toxic the drug.
Results: JWH-018 is not cytotoxic at low concentrations.
GreenScreen HC Genotoxicity Assay
This assay looks at how much a drug will interfere with our DNA. Typically, anything that damages DNA is bad news, being potentially carcinogenic, making the rationale behind this test glaringly obvious. This test was also performed in the presence of a fraction taken from liver cells, which will break down the drug. This not only checks if the drug will damage DNA, but also its breakdown products.
Results: JWH-018 does not damage DNA, so shouldn’t give you cancer.
Rat Repeat Toxicity Assay
Guess what happens in this experiment. A number of renagade lab rats looking for a bad time are rounded up and promised free drugs (kind of like Pleasure Island from Pinocchio; that shit was scary!). The rats are then dosed up and observed. Initially, they appear lethargic (read: totally baked) but a few of them died at higher doses. This appears to be down to problems breathing rather than organ toxicity, but only affected the male rats, who appeared more sensitive to the compound. The drug didn’t appear to accumulate in their systems either, but they did lose some weight, probably because they couldn’t be arsed to eat. JWH-018 showed a huge potency and was found to be tachyphylactic (my new favourite word – it means that more of a drug is required to reach the same state following an initial dosage).
Results: According to FDA guidelines, the human equivalent dose is 0.016 mg/kg but it should be tested in other species before this can be seen as reliable!
Rat Pharmacokinetics
Data is collected on a number of different “pharmacokinetic” aspects of the drug, such as how it is absorbed, distributed throughout the body, metabolised and excreted, which can help with the design of future clinical trials.
Results: JWH-018 is distributed well throughout the rat’s tissues. Metabolism and excretion are normal, with a plasma half-life of approximately 2 hours
Summary
Well, from the looks of these tests, JWH-018 seems to be pretty safe, but unless you want to piss off Ben Goldacre, it would be wise not to rely on this “test tube data” entirely. Also, like I said before, we don’t know where this data has come from, clouding the issue even further.
I've never seen 015 on the market.JWH-015 has been shown in vitro to be metabolised primarily by hydroxylation and N-dealkylation, and also by epoxidation of the naphthalene ring,[7] similar to the metabolic pathways seen for other aminoalkylindole cannabinoids such as WIN 55,212-2.[8] Epoxidation of polycyclic aromatic hydrocarbons can produce carcinogenic metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic in vivo.
\\\British Journal of Cancer (2009) 101, 940–950. doi:10.1038/sj.bjc.6605248
N Olea-Herrero1, D Vara1, S Malagarie-Cazenave1 and I Díaz-Laviada1
1Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Abstract
Background:
We have previously shown that cannabinoids induce growth inhibition and apoptosis in prostate cancer PC-3 cells, which express high levels of cannabinoid receptor types 1 and 2 (CB1 and CB2). In this study, we investigated the role of CB2 receptor in the anti-proliferative action of cannabinoids and the signal transduction triggered by receptor ligation.
Methods:
The human prostate cancer cell lines, namely PC-3, DU-145 and LNCaP, were used for this study. Cell proliferation was measured using MTT proliferation assay, [3H]-thymidine incorporation assay and cell-cycle study by flow cytometry. Ceramide quantification was performed using the DAG kinase method. The CB2 receptor was silenced with specific small interfering RNA, and was blocked pharmacologically with SR 144528. In vivo studies were conducted by the induction of prostate xenograft tumours in nude mice.
Results:
We found that the anandamide analogue, R(+)-Methanandamide (MET), as well as JWH-015, a synthetic CB2 agonist, exerted anti-proliferative effects in PC-3 cells. R(+)-Methanandamide- and JWH-015-induced cell death was rescued by treatment with the CB2 receptor antagonist, SR 144528. Downregulation of CB2 expression reversed the effects of JWH-015, confirming the involvement of CB2 in the pro-apoptotic effect of cannabinoids. Further analysing the mechanism of JWH-015-induced cell growth inhibition, we found that JWH-015 triggered a de novo synthesis of ceramide, which was involved in cannabinoid-induced cell death, insofar as blocking ceramide synthesis with Fumonisin B1 reduced cell death. Signalling pathways activated by JWH-015 included JNK (c-Jun N-terminal kinase) activation and Akt inhibition. In vivo treatment with JWH-015 caused a significant reduction in tumour growth in mice.
Conclusions:
This study defines the involvement of CB2-mediated signalling in the in vivo and in vitro growth inhibition of prostate cancer cells and suggests that CB2 agonists have potential therapeutic interest and deserve to be explored in the management of prostate cancer.
JWH-018*
1-Pentyl-3-(1-naphthoyl)indole
[Purported Ingredient of "Spice"]
July 2009Introduction:
DEA/OD/ODE
JWH-018 is a synthetic cannabinoid agonist without the classical cannabinoid chemical structure. It is used in scientific research as a tool to study the cannabinoid system. It was recently purported to be found in the herbal mixture "Spice", sold in European countries mainly via internet shops. Although JWH-018 is likely to have the same effects in humans as Δ9-tetrahydrocannabinol (Δ9-THC), the main active ingredient of marijuana, it is not controlled in the U.S.
Licit Uses:
JWH-018 is used in basic scientific research to identify cannabinoid receptors in the brain and study Δ9-THC’s mechanisms of action.
Chemistry:
1-Pentyl-3-(1-naphthoyl)indole or JWH-018 has been identified as a substance that has some pharmacological similarities to tetrahydrocannabinols contained in Cannabis sativa L. (marijuana). However, it is not related in chemical structure to tetrahydrocannabinols (THC), or other cannabinoids contained within the cannabis plant. Nor is it structurally related to other substances controlled under the CSA.
The chemical structure of JWH-018 (left) and Δ 9-THC (right), a compound found in marijuana and representative of the THC structural class, are shown below.
Based on the structural analysis, JWH-018 is not categorized as a THC substance, and is not similar in chemical structure to other substances controlled under the CSA.
Pharmacology:
Behavioral pharmacology studies show that JWH-018 has Δ9-THC-like activity in animals. In mice, it decreases overall activity, produces analgesia, decreases body temperature and produces catalepsy. Together, these four effects are used by scientists to predict Δ9-THC-like psychoactivity in humans. JWH-018’s activity in all four tests suggests that it is likely to have THC-like psychoactive effects in humans.
In vitro studies show that JWH-018 binds to the brain cannabinoid receptor CB1 with higher affinity than Δ9-THC, suggesting that it would have the same effects as Δ9-THC in vivo.
A search in the literature resulted in no published studies of the effects of JWH-018 in humans.
Illicit Uses:
JWH-018 is purported to be an ingredient in the herbal mixture "Spice" which may be smoked for its psychoactive effects. No information on the illicit use of JWH-018 in the U.S. has been identified at this time.
User Population:
Information on user population in the U.S. is very limited, and includes information from drug user internet forums. JWH-018 abuse is not monitored by any national drug abuse surveys.
Illicit Distribution:
The System to Retrieve Drug Evidence (STRIDE), a federal database for the seized drugs analyzed by DEA forensic laboratories, and the National Forensic Laboratory System (NFLIS), a system that collects drug analysis information from state and local forensic laboratories, do not contain reports of JWH-018. Seizures of herbal mixtures called "Spice" were reported in Ohio and Florida. "Spice" is purported to contain JWH-018 and other substances that are similar in pharmacological activity to Δ9-THC.
Control Status:
JWH-018 is not currently controlled under the CSA.
* NOTE: Because of an inconsistency encountered while preparing this review, identification of the correct structure corresponding to the name JWH-018 was confirmed through communication with the chemist who initially designed and synthesized this substance.
Means they should start testing and finding uses/cures for these RCs instead of banning them all because people use them to get high.this line is particularly scary:
Information on user population in the U.S. is very limited, and includes information from drug user internet forums.
Good call. They are studying the analgesic properties of JWH-018 for potential future medical applications.Means they should start testing and finding uses/cures for these RCs instead of banning them all because people use them to get high.
I am going to step out on a limb.. correct me if I am wrong. Combustion and inhalation of ANYTHING will cause cancer, no? I may be mistaken . I think marijuana produces more CO than tobacco simply because marijuana is green.Even marijuana is carcinogenic when lit of course because of carbon monoxide known as combustion... this could be avoided at all cost by using a vaporizer!
CO is the dangerous one...Even if you inhale c02 doesnt matter, after a while it will be replaced ( we always create new blood ) Its incompelte combustion which produces the real nasty stuff.
TEBOR always busting out with the outstanding articles... I never said MARY JANE was a big cancer risk... buts its more likely when not smoked in a vaporizer!Didn't the University of California conduct a case study that found marijuana isn't likely to cause cancer.
Couldnt find the study itself, but here is an article.
http://www.washingtonpost.com/wp-dyn/content/article/2006/05/25/AR2006052501729.html
One suspicion is that the THC kills aging cells before they can become cancerous.
really dude? lol hehe, im jus playinbuts its more likely when not smoked in a vaporizer!
You wanna tangle this web some morereally dude? lol hehe, im jus playin