Guineensine.

Identified in 2014 by high-content screening from black pepper, guineensine inhibits the cellular reuptake of anandamide (EC50 = 290 nM) and that of 2-AG (Nicolussi 2014). It inhibits neither FAAH nor MAGL, interacts neither with the CB1 and CB2 receptors nor with the FABP5 protein, and inhibits no serine hydrolase in activity-based profiling: it acts on the cellular transport of endocannabinoids, whose molecular target remains unknown. In BALB/c mice it produced, dose-dependently, catalepsy, hypothermia, hypolocomotion and analgesia; catalepsy and analgesia were blocked by rimonabant. In 2017, in mouse models, it reduced inflammatory pain by 95.6 % at 2.5 mg/kg and oedema by 50.0 % at 5 mg/kg intraperitoneally, and lowered pro-inflammatory cytokine production during endotoxaemia; the hypolocomotion proved CB1-independent (Reynoso-Moreno 2017). No clinical study and no pharmacokinetic or safety data in humans have been published.

Source

A natural product of the peppers of the genus Piper, absent from cannabis. This N-isobutylamide was described in the fruits of West African pepper (Piper guineense), then in long pepper (Piper longum) and black pepper (Piper nigrum), which make it a molecule of the ordinary diet.

Not characterised: no study has identified the enzymes that form guineensine. It belongs to the pepper N-isobutylamides, related to piperine through a 1,3-benzodioxole motif linked to an unsaturated chain ending in an amide.

European Union

No European control measure targets guineensine: it is not classified as a new psychoactive substance and does not appear in the schedules of the 1961 Single Convention on Narcotic Drugs. Pepper and its piperamides belong to the traditional diet of the Union and raise no question of classification. On the other hand, an ingredient isolated or strongly concentrated from Piper, promoted for its activity, would fall within the scope of Regulation (EU) 2015/2283 on novel foods and would have to be authorised before any marketing.

France

Not classified as a narcotic in France: guineensine, a pepper amide without a cannabinoid skeleton, is named in no schedule of the arrêté of 22 February 1990 and does not fall within the generic class of the benzo[c]chromene nucleus (ANSM decisions of 2024).

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

Family

ECS pharmacological tool › Transport inhibitor

Verification

Every fact on this entry was checked against its primary sources on 20 October 2026.

Wikipedia (English)

Guineesine (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. 1Nicolussi et al. 2014, Pharmacol Res: endocannabinoid reuptake inhibitor (new tab)PMID 24412246
2. 2Reynoso-Moreno et al. 2017, J Agric Food Chem: mouse models of inflammation, screening of 45 targets (new tab)PMID 28942644
3. 3Bartholomäus et al. 2019, ChemMedChem: total synthesis and structure-activity relationships (new tab)PMID 31322825
4. 4Lee et al. 2004, Planta Med: ACAT inhibitor isolated from Piper longum (new tab)PMID 15254860
5. 5Okogun & Ekong 1974, J Chem Soc Perkin Trans 1: extracts from the fruits of Piper guineense (new tab)DOI 10.1039/P19740002195
6. 6Okwute, Okogun & Okorie 1984, Tetrahedron: revised structure of guineensine (new tab)DOI 10.1016/s0040-4020(01)83507-9
7. 7PubChem, Compound Summary CID 6442405 (guineesine) (new tab)

SMILES

CC(C)CNC(=O)/C=C/C=C/CCCCCC/C=C/c1ccc2c(c1)OCO2

Machine-readable entry (JSON)

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