Since my last post about the spice behind Spice (and other smoking mixtures such as Smoke, Serenity Now, K2, Sence, etc), 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!
(Quick Update — A lot of people have been discussing and linking to this post, but there remains some suspicion that I have something to gain by saying the JWH-018 isn’t that harmful. Firstly, JWH-018 is now illegal in the UK. Secondly, as I mentioned just above this, if I have got anything wrong, please pick me up on it! If it turns out my analysis of the data is incorrect, I will correct it!)
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 coördinating 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.
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!
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
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.
Feel free to ask any questions in the comments.
Big thanks to Alfa @ Drugs-Forum.com for letting me know about these studies. You can read all about JWH-018 on their Drugs Wiki.