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JWH-018

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Collated from PsychonautWiki, Pharmacology. Where sources differ (e.g. dosing), Compare shows them side by side.

Sections
CannabinoidNaphthoylindolePW
Addiction potentialPW
moderately addictive with a high potential for abuse
ToxicityPW
exact toxic dosage is unknown
TolerancePW
full tolerance develops with prolonged and repeated use; half after 3 - 7 days; baseline after 1 - 2 weeks
Cross-tolerancePW
cannabinoids

Smoked

Route dataPsychonautWiki

Dose
WeakerStronger
ThresholdLightCommonStrongHeavy
1 mg1–2 mg2–3 mg3–5 mg—+
05 mg
LightCommonStrongHeavy
Duration
ShorterLonger
Onset5–10 minutes
Peak60–90 minutes
Offset5–10 minutes
Total1–2 hours
After-effects60–90 minutes
OnsetCome-upPeakOffset

Dangerous interactionsPW

Lithium

Mechanism of actionPH

... JWH-018 is probably the most studied synthetic cannabinoid. It has been found in multiple preparations and has been shown to be a potent cannabinoid receptor (CB) agonist. CB1 is the principal receptor thought to be most highly responsible for the euphoria and psychoactive effects of THC. The CB2 receptor resides mostly in the immune system but has some effect on pain control and mood regulation. ...
/Synthetic cannabinoid/ agonistic activity on the CB1 receptor is responsible for elevating mood and inducing a feeling of well-being. Some /synthetic cannabinoid/ users have reported effects similar to or even stronger than those obtained by smoking cannabis, such as physical relaxation, changes in perception, and mild euphoria. The higher potency of action of these synthetic cannabinoids might be explained by in vitro experiments that have suggested that, while THC acts as a partial agonist on the CB1 receptor, JWH-018 acts as a full and potent agonist. Moreover, compared with THC, JWH-018 possesses approximately a fourfold higher affinity to the cannabinoid CB1 receptor and 10-fold higher affinity to CB2 receptor.
... JWH-018 (naphthalen-1-yl-(1-pentylindol-3-yl)methanone) was first synthesized during an analysis aiming at developing new cannabimimetic indole compounds with potential therapeutic effects comparable with those of THC. It belongs to the aminoalkylindole family and has been shown to have a binding affinity for the CB1 receptors in the low nanomolar range (approximately 9 nM). In cannabinoid receptor expressing CHO cells, JWH-018 inhibits forskolin-stimulated cAMP production, whereas in HEK293 cells stably expressing this receptor, it was recently found to activate multiple cannabinoid receptor signaling pathways, including the phosphorylation of ERK1/2 mitogen activated protein kinase and the internalization of CB1 receptors.
JWH-018 dose-dependently inhibits glutamate release in autaptic excitatory hippocampal neurons, probably acting on the CB1 receptor, an effect reversed by administration of the CB1 receptor antagonist rimonabant. In vivo studies showing that JWH-018 induces analgesia, catalepsy, hypomotility, and hypothermia, namely the tetrad of behaviors classically caused by cannabinoids administration, have confirmed that this compound acts as a potent and effective CB1 receptor agonist. Specifically, JWH-018 displayed fourfold affinity to the CB1 receptor and about 10-fold affinity to the CB2 receptor compared with THC. It is worth nothing that unlike metabolites of most synthetic cannabinoids, JWH-018 hydroxylated metabolites retain in vitro and in vivo activity at CB1 receptors, a finding that in conjunction with the higher CB1 receptor affinity and activity relative to THC may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to marijuana.

Pharmacokinetics

AbsorptionPH

The duration of effects in humans compared to THC seems to be shorter for JWH-018 (1-2 hours) and considerably longer for CP 47,497-C8 (5-6 hours), as reported in a self-experiment.

MetabolismPH

... The high pharmacological and addictive potency of JWH-018 highlights the importance of elucidating the metabolism of JWH-018, without which a meaningful insight into its pharmacokinetics and its toxicity would not be possible. In the present study, the cytochrome P450 phase I metabolites of JWH-018 were investigated, after in vitro incubation of the drug with human liver microsomes, followed by liquid chromatography-tandem mass spectrometry analysis. This revealed monohydroxylation of the naphthalene ring system, the indole moiety, and the alkyl side chain. In addition, observations were made of dihydroxylation of the naphthalene ring system, and the indole moiety, or as result of a combination of monohydroxylations of both the naphthalene ring system and the indole moiety or the alkyl side chain, or a combination of monohydroxylations of both the indole ring system and the alkyl side chain. There is also evidence of trihydroxylation at different locations of the hydroxyl groups in the molecule. Furthermore, dehydration of the alkyl side chain, in combination with both monohydroxylation and dihydroxylation as well as arene oxidation of the naphthalene ring system, combined with both monohydroxylation and dihydroxylation at different sites of oxidation were found. N-dealkylation also in combination with both monohydroxylation and dihydrodiol formation of the N-dealkylated metabolite was detected. Finally, a metabolite was found carboxylated at the alkyl side chain.
... This study evaluates nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes for their ability to glucuronidate hydroxylated metabolites of 1-naphthalenyl-1(1-pentyl-1H-indol-3-yl)-methanone (JWH-018) and (1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073), the two most common synthetic cannabinoids found in K2 products. Conjugates were identified and characterized using liquid chromatography/tandem mass spectrometry, whereas kinetic parameters were quantified using high-performance liquid chromatography-UV-visible methods. UGT1A1, UGT1A3, UGT1A9, UGT1A10, and UGT2B7 were shown to be the major enzymes involved, showing relatively high affinity with K(m) ranging from 12 to 18 uM for some hydroxylated K2s. These UGTs also exhibited a high metabolic capacity for these compounds, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body. ...
The aim of this study was to elucidate the metabolism of JWH-018. An ethanolic extract was prepared from an incense containing large amounts of JWH-018. After removal of the ethanol, the residue was given to Wistar rats by gastric intubation and urine was collected over 24 hours. For identification, the metabolites were isolated after enzymatic or acidic cleavage of conjugates by liquid-liquid extraction (LLE) or solid-phase extraction (C18) followed by acetylation. The metabolites were separated and identified by GC and MS in the electron ionization (EI) mode. The parent compound JWH-018 could be found in the urine extracts only in small amounts. Besides the parent compound, the N-dealkylated metabolite could be detected in urine in small amounts. The highest signals could be observed for the hydroxylated N-dealkyl metabolites. Hydroxylation can take place in both aromatic systems, the naphthalene and the indole part, which could be shown by mass shift of the corresponding fragments. JWH-018 is extensively metabolized in rats. According to our experience similar metabolic patterns can be expected in humans. ...
... It is worth nothing that unlike metabolites of most synthetic cannabinoids, JWH-018 hydroxylated metabolites retain in vitro and in vivo activity at CB1 receptors...
For more Metabolism/Metabolites (Complete) data for 1-pentyl-3-(1-naphthoyl) indole (9 total), please visit the HSDB record page.

Plan when to take JWH-018 — see where onset, peak and comedown land on the clock

Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.