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Part II Doctrine of Ismailism Chapter I Potentiality and Actuality Chapter II Existence in Power Chapter Existence in Actio by force Chapter IV Knowledge of Truth Chapter V Implementation of faith by Action A Shariat 1 Islam 2 Imam B Tariquat 1...


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Written by Headspin on 2010-06-25 07:38:37




Heightened Senses
Light Analgesia
Good Body High
Small doses


Difficulty Concentrating
Vivid Vision
Increased Heart Rate (tachycardia)
Increase in Blood Pressure
Increase in Appetite (uncommon)
Dry Mouth
Itchy skin


Rapid thinking

Severe Effects

High increase in Heart Rate and/or Blood Pressue
Muscular Tension


Due to the high potency of this compound, it can be difficult to properly titrate dosage, resulting in a minor overdose. These over dose experiences can be very negative for the user, with effects including extreme anxiety, confusion, and fear, even in experienced users of marijuana.

Methods of Ingestion

- Vaporize the product off of tin foil or in a lightbulb vaporizor.
- Top off an herbal blend in a pipe.
- Place x amount in the end of a cigarette.

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. It is covered by US patent #7241799.

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

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)
- CYP2C9 (at 7.1% the potency of the reference compound, sulphaphenazole)
- CYP2C19 (at 357.1% the potency of the reference compound, tranylcypromine)
- CYP3A4 (at 0.625% the potency of the reference compound, ketoconazole)

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.

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).

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.

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. 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.

Metabolism of JWH-018

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

Half-Life of JWH-018

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


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. 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. 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. 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.

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.


Male rats have been shown to possess greater sensitivity to JWH-018 than their female counterparts. 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.

Producing JWH-018

John W. Huffman has been quoted as saying that, "It [JWH-018] is really easy to make". 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".

Chemical characteristics

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


White solid
Note: The degradation of indole compounds such as JWH-018 results in a yellow-brown, gummy appearance due to melting point suppression. 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%.

Spice Products

Spice, Spice Silver, Spice Gold, Spice Diamond, Spice Tropical Synergy and Spice Arctic Synergy have all been confirmed in at least some analyses to contain JWH-018, though not always as the only or primary active ingredient.

Other JWH-018 containing herbal blends

Buddha Melt
Buddha Blend
Smoke X, XX, & XXX
Chillin XXX
Spicey XXX
ZoHai SX
Smoke Plus
Skunk ANBow

Legal status of JWH-018

JWH-018 is illegal in Argentenia.

JWH-018 is illegal in Austria.

JWH-018 not illegal in Brazil.

JWH-018 falls under item 1 of Schedule 2 of the Controlled Drugs and Substances Act which lists similar synthetic preparations of ∆-9-THC and other Cannabinoids.

Channel Islands
Sale of the smoking blend Spice has been banned from commercial shops in the Channel Islands. JWH-018 itself is not scheduled or controlled.

JWH-018 is illegal in Chile.

JWH-018 is illegal in France as of February 24th, 2009.

JWH-018 is illegal in Germany as of January 22nd, 2009.

JWH-018 is illegal in Luxembourg.

JWH-018 is illegal in the Netherlands.

JWH-018 is illegal in Poland as of May, 2009.

JWH-018 is illegal in Romania.

Smoking mixtures, including AM-HI-CO, Dream, Spice (Gold, Diamond), Zoom, Ex-ses, Pep Spice, Yucatan Fire and others are considered controlled substances, however JWH-018 and other synthetic Cannabinoid agonists have not been directly declared as scheduled or illegal.

United Kingdom
JWH-018 Scheduling in the United Kingdom is imminent. The ACMD have released wording of analogue style laws which will cover a variety of cannabinoids including JWH-018. This is expected to be written into law in early 2010 subject to parliamentary approval.

United States
JWH-018 is not considered a structural/positional isomer of any scheduled compound, including ∆-9-THC and HU-210 (both Schedule I substances). It may however fall under the analogue act due to its similar activity to these compounds.

Special Thanks To The Users of and

Written by Headspin


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