RCS-4.

RCS-4 differs from the other synthetic cannabinoids in its genealogy: no design paper was found for it, whereas the JWH and CP series come out of published research programmes. It was reported in 2010 to the European early warning system by Hungary, then identified in Ireland, Germany, the United States and Belgium in plant-based products (Kavanagh et al., 2012; Simolka et al., 2012; Logan et al., 2012; Denooz et al., 2013). Its structure is that of an N-pentylated indole linked by a ketone to a phenyl bearing a methoxy at the para position, where JWH-018 carries a naphthalene. On recombinant human CB1 receptors, Gatch and Forster (2016) measure a Ki of 22.5 nM and an EC50 of 20 nM, with a maximal effect of 100.6% of that of CP 55,940: a full agonist, whereas Δ9-THC is only a partial agonist (Fantegrossi et al., 2014, a class-level finding). In rats trained to discriminate Δ9-THC, it substitutes for THC with an ED50 of 37.9 mg/kg, the least potent of the six molecules tested; in mice, it depresses locomotor activity with an ED50 of 5.54 mg/kg. Its fate in the body is better characterised: eighteen metabolites were identified in human hepatocytes, O-demethylation being the most common transformation and giving the major metabolite (Gandhi et al., 2014), and the parent molecule was not detected in the urine of patients (Kavanagh et al., 2012). No controlled human study was found: neither dose, tolerance nor dependence is characterised.

Source

An entirely synthetic molecule, absent from hemp as from any living organism. It was identified in plant-based products sold as incense or smoking mixtures, in Germany in 2011 (Simolka et al., 2012), in the United States (Logan et al., 2012) and in Belgium (Denooz et al., 2013). It is among the 22 synthetic cannabinoids sought by a validated method in hair, alongside its ortho isomer (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 concerns hemp or cannabidiol products.

No biological pathway: RCS-4 is entirely synthetic, with no plant precursor or enzymatic step. 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

RCS-4 is classed 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 « RCS-4 ou 1-pentyl-3-(4-méthoxybenzoyl) indole », as an example (« notamment ») of the generic family of « indol-3-yl methanone »: a substituent on the indole nitrogen of the alkyl, haloalkyl, halobenzyl, alkenyl, cycloalkylmethyl, cycloalkylethyl, methyl-oxane, 1-(N-methylpiperidin-2-yl)methyl or 2-(4-morpholinyl)ethyl type, and a group of the naphthyl, benzyl, phenyl, cyclopropyl or adamantyl type on the carbon of the methanone bridge. This family was introduced into annex IV by the decree of 31 March 2017 (JORF of 6 April 2017), whose text, re-read, already cites RCS-4. The clause covering tetrahydrocannabinols (annex III since the decision of 6 February 2026) therefore does not apply. Production, possession, supply, transport and use fall under narcotics criminal law.

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

Family

Synthetic CB receptor agonist › New psychoactive substance

Class

benzoylindole

Verification

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

Wikipedia (English)

RCS-4 (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. 1Gatch MB, Forster MJ. Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. Psychopharmacology (Berl). 2016;233(10):1901-1910 (table 1: Ki 22.5 nM, EC50 20 nM, maximal effect 100.6% at human CB1; ED50 in the rat and the mouse) (new tab)PMID 26875756
2. 2Gandhi AS, Zhu M, Pang S, Wohlfarth A, Scheidweiler KB, Huestis MA. Metabolite profiling of RCS-4, a novel synthetic cannabinoid designer drug, using human hepatocyte metabolism and TOF-MS. Bioanalysis. 2014;6(11):1471-1485 (new tab)PMID 25046048
3. 3Kavanagh P, Grigoryev A, Melnik A, Simonov A. The identification of the urinary metabolites of 3-(4-methoxybenzoyl)-1-pentylindole (RCS-4), a novel cannabimimetic, by gas chromatography-mass spectrometry. J Anal Toxicol. 2012;36(5):303-311 (first notification to the EMCDDA in 2010) (new tab)PMID 22582265
4. 4Simolka K, Lindigkeit R, Schiebel HM, Papke U, Ernst L, Beuerle T. Analysis of synthetic cannabinoids in « spice-like » herbal highs: snapshot of the German market in summer 2011. Anal Bioanal Chem. 2012;404(1):157-171 (new tab)PMID 22710567
5. 5Hutter 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 (LOQ 0.5 pg/mg for RCS-4 and its ortho isomer, read from Florou and Boumba 2021, Toxicol Rep, PMID 34646750) (new tab)PMID 22835826
6. 6Logan BK, Reinhold LE, Xu A, Diamond FX. Identification of synthetic cannabinoids in herbal incense blends in the United States. J Forensic Sci. 2012;57(5):1168-1180 (new tab)PMID 22834927
7. 7Denooz R, Vanheugen JC, Frederich M, de Tullio P, Charlier C. Identification and structural elucidation of four cannabimimetic compounds (RCS-4, AM-2201, JWH-203 and JWH-210) in seized products. J Anal Toxicol. 2013;37(2):56-63 (new tab)PMID 23339188
8. 8Fantegrossi WE, Moran JH, Radominska-Pandya A, Prather PL. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: mechanism underlying greater toxicity? Life Sci. 2014;97(1):45-54. CLASS datum (full agonism of the synthetic cannabinoids versus partial agonism of THC), not specific to RCS-4. (new tab)PMID 24084047
9. 9Zangani C et al. The e-Psychonauts' 'Spiced' World: assessment of the synthetic cannabinoids' information available online. Curr Neuropharmacol 2020 (RCS-4 in the UNODC, EUDA and NPSFinder lists) (new tab)PMID 32116194
10. 10ANSM, consolidated list of substances classified as narcotics, updated 16 February 2026 (annex IV, « indol-3-yl methanone » family, RCS-4 cited as an example) (new tab)
11. 11Order of 31 March 2017 amending the order of 22 February 1990: « indol-3-yl methanone » family of annex IV, RCS-4 cited (Légifrance, JORF of 6 April 2017) (new tab)
12. 12PubChem CID 56841530, RCS-4: identifiers, average mass 321.4 (new tab)

SMILES

CCCCCN1C=C(C2=CC=CC=C21)C(=O)C3=CC=C(C=C3)OC

Machine-readable entry (JSON)

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