APP-CHMINACA.Also known as PX-3

APP-CHMINACA is a synthetic cannabinoid receptor agonist of the indazole-3-carboxamide family, introduced in 2009 in Pfizer patent applications before being identified on the new psychoactive substances market. The published binding data give it an affinity of 9.81 nM at CB1 and 4.39 nM at CB2; a [35S]GTPγS functional assay gives the (S)-enantiomer a potency of 251 nM at CB1 and 8.09 nM at CB2, and the (R)-enantiomer is far less active. Two metabolism studies, one on human liver microsomes (Presley et al., 2020), the other combining in vitro and in vivo models (Camuto et al., 2025), describe a transformation dominated by hydrolysis of the terminal amide and hydroxylation of the cyclohexyl ring, and propose the corresponding analytical markers. By contrast, no clinical pharmacology study was found, no series of poisonings is attributed to it alone, and human data are lacking: what is known comes from seizures, forensic work and a poisoning episode in Alaska in which it figured among the molecules found.

Source

An entirely synthetic molecule, absent from cannabis and from any living organism. It appeared on the new psychoactive substances market, where it was seized as a powder in a parcel from China declared as « white pigments » (Lobo Vicente et al., 2016) and found in products collected in Anchorage, Alaska, in 2015 and 2016 (Springer et al., 2016). Finished products do not carry its name: the people exposed most often do not know which molecule they are consuming nor in what amount.

No biological pathway: the molecule is produced by no plant or living organism. It belongs solely to synthetic chemistry, with no link to the cannabigerol pathway that produces the cannabinoids of hemp.

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 ties it to a generic definition by chemical family in annex IV of its list (see the French status).

France

APP-CHMINACA is named in no entry of the consolidated ANSM list (updated 16 February 2026), which does, however, cite the neighbouring molecules 5F-APP-PINACA (PX-2) and 5F-APP-PICA (PX-1). By its structure it falls under the generic family of the « 3-carboxamide indazole derivatives » of annex IV, which the text of the decree of 3 October 2017 (JORF of 10 October 2017) already contains: a substituent on nitrogen 1 of the indazole of the alkyl, haloalkyl, halobenzyl, cycloalkylmethyl or related type, an indazole ring substituted or not, and a carboxamide-bridge nitrogen bearing in particular a 1-amino-1-oxo group substituted at position 3 by an alkyl, a cycloalkyl or a phenyl. APP-CHMINACA (cyclohexylmethyl on nitrogen 1, phenylalaninamide head) shares this head with PX-2, cited as an example. This is a reading of the text applied to the structure, not a nominative listing. The entry « Tétrahydrocannabinols, leurs esters, éthers, sels » (annex III since the decision of 6 February 2026) does not apply: the molecule is not a THC derivative. Use, possession, transfer and trafficking of narcotics are criminally punished.

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

Family

Synthetic CB receptor agonist › New psychoactive substance

Class

indazole-3-carboxamide

Verification

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

Wikipedia (English)

PX-3 (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. 1Schoeder CT, Hess C, Madea B, Meiler J, Müller CE. Pharmacological evaluation of new constituents of Spice: synthetic cannabinoids based on indole, indazole, benzimidazole and carbazole scaffolds. Forensic Toxicol. 2018 (APP-CHMINACA: Ki CB1 9.81 nM, CB2 4.39 nM; introduced by Buchler et al.) (new tab)PMID 29963207
2. 2Doi T, Tagami T, Takeda A, Asada A, Sawabe Y. Evaluation of carboxamide-type synthetic cannabinoids as CB1/CB2 receptor agonists: difference between the enantiomers. Forensic Toxicol. 2018 (EC50 in [35S]GTPγS of the (S) and (R) enantiomers of APP-CHMINACA) (new tab)PMID 29367862
3. 3Presley BC, Logan BK, Jansen-Varnum SA. In Vitro Metabolic Profile Elucidation of Synthetic Cannabinoid APP-CHMINACA (PX-3). J Anal Toxicol. 2020;44:226-236 (new tab)PMID 31665324
4. 4Camuto C, De-Giorgio F, Corli G, Bilel S, Mazzarino M, Marti M, Botrè F. Metabolic profiling of the synthetic cannabinoid APP-CHMINACA (PX-3) as studied by in vitro and in vivo models. Forensic Toxicol. 2025 (new tab)PMID 39576558
5. 5Lobo Vicente J, Chassaigne H, Holland MV, Reniero F, Kolář K, Tirendi S, Vandecasteele I, Vinckier I, Guillou C. Systematic analytical characterization of new psychoactive substances: a case study. Forensic Sci Int. 2016;265:107-115 (identification of PX-3 and 5F-AMB in a Belgian customs seizure) (new tab)PMID 26874735
6. 6Springer YP, Gerona R, Scheunemann E, et al. Increase in Adverse Reactions Associated with Use of Synthetic Cannabinoids, Anchorage, Alaska, 2015-2016. MMWR Morb Mortal Wkly Rep. 2016;65(40):1108-1111 (APP-CHMINACA among eleven synthetic cannabinoids identified) (new tab)PMID 27736839
7. 7Brandon AM, Antonides LH, Riley J, Epemolu O, McKeown DA, Read KD, McKenzie C. A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists. Molecules. 2021 (microsomal half-life value for APP-CHMINACA reproduced as a literature comparison, table 6) (new tab)PMID 33807614
8. 8Mercier 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
9. 9Zangani C et al. The e-Psychonauts' 'Spiced' World: assessment of the synthetic cannabinoids' information available online. Curr Neuropharmacol 2020 (APP-CHMINACA 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, family of 3-carboxamide indazole derivatives; APP-CHMINACA not named) (new tab)
11. 11Légifrance, order of 3 October 2017 amending the order of 22 February 1990 setting the list of substances classified as narcotics, annex IV (JORF of 10 October 2017) (new tab)

SMILES

C1CCC(CC1)CN2C3=CC=CC=C3C(=N2)C(=O)N[C@@H](CC4=CC=CC=C4)C(=O)N

Machine-readable entry (JSON)

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