Great JWH-018 Info

July 6, 2010

Introduction to JWH-018 (1-pentyl-3-(1-nahpthoyl)indole)

JWH-018 (1-pentyl-3-(1-naphthoyl)indole) is a synthetic aminoalkylindole Cannabinoid agonist which acts at both the CB1 and CB2 receptors, with a moderate selectivity for the CB2 receptor [1]. It is covered by US patent #7241799 [35]

Synthesized primarily for radioligand binding studies, JWH-018 (named after it’s creator, John W. Huffman) has shown in vivo and in vitro activity [1] similar to that of the classic exogenous agonist of Cannabinoid receptors, ∆-9-THC, though it is considerably (4-5x) more potent [5].

Pharmacology and Pharmacokinetics of JWH-018

Enzyme Inhibition by JWH-018

JWH-018 has been shown to inhibit the following enzymes:

- CYP1A2 (at 20.7% the potency of the reference compound, alpha-naphtoflavone) [11]
- CYP2C9 (at 7.1% the potency of the reference compound, sulphaphenazole) [11]
- CYP2C19 (at 357.1% the potency of the reference compound, tranylcypromine) [11]
- CYP3A4 (at 0.625% the potency of the reference compound, ketoconazole) [11]

Cannabinoid Receptor (CB1/CB2) Binding of JWH-018

The Ki (binding affinity) values for primary cannabinoid (CB1/CB2) receptors are 9.00±5.00 and 2.94±2.65 nM, respectively, showing a general selectivity for the CB2 receptor over the CB1 receptor. The Ki ratio for the receptors is thus CB1:CB2, 3.06 [1].

Molecular Pharmacology of JWH-018

Though based on the structure of WIN 55,212-2, the JWH analogues lack a methyl group at C-2. Various N-Alkyl side chains define the various JWH analogues, which range from N-Propyl (JWH-072) to N-Hexyl (JWH-019) and of course N-Pentyl (JWH-018). The N-Pentyl substitute on the compound reduced CB2 selectivity as compared to N-Butyl substitute (JWH-073, which has a CB1:CB2 affinity ratio of 0.23) [1].

In terms of the structure-activity-relationship (SAR) between CB receptors and their ligands, some primary components are necessary for a best-fit-alignment scenario: the cyclohexene and naphthalene ring, the phenolic hydroxyl and carbonyl group, the carbon side chain at C-3 and the morpholinoethyl group. In the case of JWH-018, the morpholinoethyl group has been replaced with the N-Pentyl side chain, which exhibits similar steric and electrostatic properties as the morpholinoethyl group [1].

N-Alkyl chains of increasing length have been shown to increase binding affinity to CB2 receptors, and are maximized by the 4 and 6 carbon chains of JWH-018, JWH-007, JWH-048, JWH-081 and JWH-098 [3]. Compounds with shorter carbon chain lengths exhibited weak binding affinities and no in vivo activity (JWH-070, JWH-077, and JWH-043), as has also been shown with other CB agonists [4].

Metabolism of JWH-018

No accumulation of JWH-018 in peripheral tissues or albumin deposits was shown after 7 days of chronic dosing [8]. Bi-phasic distribution was shown for JWH-018 metabolism, suggesting that the drug undergoes both metabolism and elimination phases [6].

Half-Life of JWH-018

The half-life of JWH-018 is approximately two hours (112.2min) [6].

JWH-018 exhibits a traditional tachyphylactic response in repeated dosing, with a notable decrease in both effect and duration after 3 days of chronic dosing [8]. This tolerance is likely the result of CB1/2 receptor downregulation, similar to the tolerance developed from ∆-9-THC or Cannabis administration as discussed here under the Tolerance heading and in much greater detail in a dedicated thread here: Cannabis and Cannabinoid Tolerance.

The health risks of JWH-018


JWH-018 has been shown not to bind to hERG, the human gene encoding for cardiovascular potassium channels [12]. It is thus unlikely to cause an increased QT interval, which could have deleterious and possibly deadly effects on the cardiovascular system.

At the highest tested laboratory dose (10mg/kg) some respiratory depression was shown, which resulted in some animal deaths [6][8]. The deaths were attributed to catatonia and respiratory depression, as no organ toxicity was detected.


JWH-018 has been shown not to cause direct cell-death [10].

Carcinogenic/Mutagenic Properties

JWH-018 has been shown not to interfere with DNA in vivo. The combustion products of the material are still unknown and have not been tested for potential mutagenic or carcinogenic properties, but P.O. administration has been shown to not result in genotoxicity [9].


Male rats have been shown to possess greater sensitivity to JWH-018 than their female counterparts [6][8]. This may potentially translate to an increased sensitivity in male humans as compared to females, though abnormalities in CB1/CB2 receptor distribution in male and female rats have been demonstrated in previous studies [8].

Producing JWH-018

John W. Huffman has been quoted as saying that, “It [JWH-018] is really easy to make”[5]. A synthesis of the related compounds can be found in paper entitled “Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists” [36].

Forms of JWH-018

Pure JWH-018

Chemical characteristics
CAS#: 209414-07-3 [2]
Formula: C24H23NO [1][2][6]
Mol. Weight: 341.5 g/mol [1][2][6]
Solubility in water: Not soluble in water at 25ºc [2]
Soluble in nonpolar solvents: Soluble in DMF (dimethylformamide), DMSO (dimethyl sulfoxide), EtOH (ethanol)[2]
Ion classification: 1 (Highly Ionizable)[6].


White solid [6][7]
Note: The degradation of indole compounds such as JWH-018 results in a yellow-brown, gummy appearance due to melting point suppression [33]. Samples of JWH-018 circulating as a gummy, rust-brown solid are highly oxidized samples of the compound, though appear to have degraded less than 5% [34].

What is it? JWH-018

July 6, 2010

Disclaimer!!! This is solely an informational document about making inexpensive incense blends for the home and the research of JWH-018.  This is for research use only


With all the recent buzz in regards to this so called synthetic marajuana I became intrigued as to why anyone would go through the trouble of making a synthetic marijuana.  This led me on a really fun journey!  JWH-018 is the leading product contained in all sorts of legal smoking blends such as spice, k2 and serenity.  JWH-018 was first synthesized by the well-known Clemson University organic chemist, Prof John W Huffman: the eponymous JWH-018. Another compound, found in Spice products sold in Germany, is an analog of CP-47,497, a cannabinoid developed by Pfizer over 20 years ago.

So how does it work?  Well here is one way you to can have fun with JWH-018.

First of all, you must obtain 1 gram of JWH-018.  I use because of the great quality JWH-018 and the same day shipping.  Product has never been an issue for me here.

You’ll want to obtain some good herbal substrate. K2, Serenity now, and other use complex herb mixtures, but I would recommend either mullein or marshmallow leaves as a substrate. they are very mellow, burn smoothly, and have a nice aroma. Get a pound, it’s super cheap, usually like 10-20 dollars, and that is enough to do SEVERAL batches.

You’ll need some acetone. Just be ABSOLUTELY certain it doesn’t contain any denaturing agents. If it contains them, you’re gonna have a bad time! The ones listed below are free of denaturing agents!

You’ll also need an acetone proof spray bottle. This is important. Acetone will eat like acid through most plastics. You want, preferably a high density poly-ethylene (HDPE) spray bottle. Again, I have some good acetone safe spray bottles listed below

You’ll also need a measuring cup that will do ml’s.

a scale that can weigh around 100g accurately.

and a glass baking dish.

First, measure out 4ml of acetone, and dissolve your gram of jwh-018 into it. If it wont completely disovle, add acetone a little at a time until it does, then place the acetone in the spray bottle. (Okay, I’ve received a lot of questions about this, 4ml IS enough to disolve the jwh-018, but it is a small amount to use in the spray bottle, especially if using a larger spray bottle. If you wish to make it easier to handle, increase the amount of acetone to ~50ml. This will not effect the potency of your blend, it will just take it longer to dry. OR alternatively, you can look for a smaller hdpe spray bottle.)

The amount of herb that you use will define the strength of the mixture. 100g will make it 10mg/g, which is a little on the weak side, and 50g will make it 20mg/g which is quite strong, like k2 summit. I prefer somewhere in the middle so I usually use 75 grams of herb which makes it about 15 mg/g.

However much you decide to use, spread it out in your glass baking dish.

Now this is the most dangerous part. You must spray the leaves as evenly as possible, or you can get “hotspots” or localized areas in your mixture that have much higher concentrations of jwh-018 that can be dangerous. So, set your spray nozzle to as fine a spray as possible, and spray a few times to just moisten the surface, stir up your leaves, spray again, stir, spray again, and so on until all the acetone is gone.

Then set the baking dish in a cool dry place until all the smell from the acetone is gone. I usually leave it overnight. It is very important that all of the acetone is evaporated, acetone isn’t good for you!

Once it is dry, you have your very own jwh-018 incense blend.

There are also other ways to smoke JWH-018

Another way which is becoming more and more popular is taking small and I mean very small amounts around 4-5mg or so and put it in the tip of a cigarette.  This will get you nice and high very quickly.   Remember to use a very small amount as some people say they get to high and have a really bad trip so take it slow.


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