JWH-398.

JWH-398 is the 4-chlorinated analogue of JWH-018, and it illustrates what a single atom can change in recognition by a receptor. The study published in 2012 by Jenny L. Wiley, John W. Huffman and colleagues compared, in the same experiment, the four halogens at position 4 of the naphthalene: chlorine gives 2.3 ± 0.1 nM at CB1 and 2.8 ± 0.2 nM at CB2, bromine 1.2 nM, iodine 2.5 nM and fluorine 7.2 nM at CB1, whereas unsubstituted JWH-018 lies at 9 ± 5 nM. The authors' conclusion is that moderate electronegativity favours CB1 affinity, and chlorine lies near this optimum. The molecule is therefore a high-affinity agonist of both receptors, with no marked selectivity, which produces the effects of the cannabinoid tetrad in mice; Δ9-THC is only a partial agonist. Nothing is published on TRPV1, GPR55, PPARγ or 5-HT1A, and there is no controlled study in humans: neither dose, tolerance nor dependence is characterised. The molecule is classified as a narcotic in France under its own name, and named in the 2012 US federal Synthetic Drug Abuse Prevention Act (Howlett et al., 2021).

Source

An entirely synthetic molecule, absent from hemp and from any living organism. It figures among the synthetic cannabinoids sought in the hair of consumers of Spice-type mixtures (Hutter et al., 2012) and in the lists of the EUDA and of UNODC recording the synthetic cannabinoids reported (Zangani et al., 2020). None of this relates to hemp or to cannabidiol products.

No known biosynthetic pathway: the molecule is produced by no plant or living organism. It belongs solely to synthetic chemistry, described here by chemical class only.

European Union

The substance is not listed in the Annex to Council Framework Decision 2004/757/JHA (consolidated version of 12 January 2026), which lists the new psychoactive substances controlled at European Union level; control is a matter for national law. It appears in the lists of the EUDA and of UNODC recording the synthetic cannabinoids reported (Zangani et al., 2020), which is monitoring and not control. It does not appear in the schedules of the 1971 Convention on Psychotropic Substances (green list of the INCB, 35th and 36th editions). France cites this molecule by name in annex IV of its list.

France

JWH-398 is classified as a narcotic in France, and cited under its own name. The ANSM consolidated list (updated 16 February 2026) cites it in annex IV, under the entry « JWH-398 ou 1-pentyl-3-(4-chloro-1-naphthoyl) indole », as an example (« notamment ») of the generic family of the « indol-3-yl methanones » (a substituent on the indole nitrogen of the alkyl, haloalkyl, cycloalkylmethyl or related type, and a naphthyl, benzyl, phenyl, cyclopropyl or adamantyl group, substituted or not, on the carbon of the methanone bridge), introduced into annex IV by the decree of 31 March 2017 (JORF of 6 April 2017). The same list cites alongside it other halogenated naphthoylindoles, including JWH-387 (4-bromo) and JWH-412 (4-fluoro). The clause on tetrahydrocannabinols (annex III since the decision of 6 February 2026) does not apply. Production, possession, transfer, transport and use fall under the criminal law on narcotics.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Family

Synthetic CB receptor agonist › New psychoactive substance

Class

naphthoylindole

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

JWH-398 (new tab)

Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.

1. 1Wiley JL, Smith VJ, Chen J, Martin BR, Huffman JW. Synthesis and pharmacology of 1-alkyl-3-(1-naphthoyl)indoles: steric and electronic effects of 4- and 8-halogenated naphthoyl substituents. Bioorg Med Chem. 2012;20(6):2067-2081 (table 1: JWH-398, Ki CB1 2.3 nM, CB2 2.8 nM) (new tab)PMID 22341572
2. 2Hutter M, Kneisel S, Auwärter V, Neukamm MA. Determination of 22 synthetic cannabinoids in human hair by liquid chromatography-tandem mass spectrometry. J Chromatogr B. 2012;903:95-101 (new tab)PMID 22835826
3. 3Howlett AC, et al. The Spicy Story of Cannabimimetic Indoles. Molecules 2021 (JWH-398 named in the 2012 US act) (new tab)PMID 34684770
4. 4Mercier G, Mohamed KA, Zagzoog A, et al. In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors. Neurochem Int. 2025 (abstract: class toxicities) (new tab)PMID 40876783
5. 5Zangani C et al. The e-Psychonauts' 'Spiced' World: assessment of the synthetic cannabinoids' information available online. Curr Neuropharmacol 2020 (JWH-398 in the UNODC, EUDA and NPSFinder lists) (new tab)PMID 32116194
6. 6ANSM, consolidated list of substances classified as narcotics, updated 16 February 2026 (annex IV, « indol-3-yl methanone » family, JWH-398 cited as an example) (new tab)
7. 7Order of 31 March 2017 amending the order of 22 February 1990: « indol-3-yl methanone » family of annex IV (Légifrance, JORF of 6 April 2017) (new tab)
8. 8PubChem, Compound Summary CID 57458928, JWH-398 (new tab)

SMILES

CCCCCN1C=C(C2=CC=CC=C21)C(=O)C3=CC=C(C4=CC=CC=C43)Cl

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.