{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"VWVIOABMCXYUAS-RBUKOAKNSA-N","prefName":"KLS-13019","symbol":"KLS-13019","iupacName":"1-[3-[[3,5-dihydroxy-4-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]phenyl]methyl]azetidin-1-yl]ethanone","aliases":["KLS-13019","KLS 13019"],"cas":"1801243-39-9","pubchemCid":"91824155","chebiId":null,"smiles":"CC1=C[C@H]([C@@H](CC1)C(=C)C)C2=C(C=C(C=C2O)CC3CN(C3)C(=O)C)O","molecularFormula":"C22H29NO3","molecularWeight":355.5,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/91824155"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":null},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"No biosynthetic pathway: the molecule comes from no living organism. It is obtained by organic synthesis, by attaching a nitrogen-containing side chain to the resorcinol before coupling to the terpene fragment of cannabidiol.","originNote":"A fully synthetic molecule: a structural analogue of cannabidiol whose pentyl chain is replaced by a polar acetyl-azetidine group. It was designed by the team of William Kinney and Douglas Brenneman at the company Kannalife (KLS).","discovered":""},"pharmacology":{"summaryFr":"KLS-13019 is a synthetic analogue of cannabidiol whose pentyl chain is replaced by a more polar acetyl-azetidine group. Described in 2016 by Kinney, Brenneman and colleagues, it proved 50 times more potent than CBD in protecting hippocampal neurons from ammonium and ethanol toxicity; a 2018 comparison gives a factor of 31. Its mechanism involves the mitochondrial sodium-calcium exchanger and antagonism of the GPR55 receptor, with no activity at opioid receptors. In mice, like CBD, it prevented paclitaxel-induced mechanical sensitivity and, unlike CBD, reversed sensitivity that was already established. In rats, a 2024 study reports a dose-dependent reversal of paclitaxel-induced allodynia, by the intraperitoneal as well as the oral route. The compound remains at the preclinical stage.","receptorSummaryFr":"KLS-13019 is described as an antagonist of the GPR55 receptor: in a β-arrestin assay on human GPR55, it behaves as an antagonist with no agonist activity. Like cannabidiol, its neuroprotective effect depends on the mitochondrial sodium-calcium exchanger, since an inhibitor of this exchanger abolishes it. Unlike CBD, its neuroprotection is not attenuated by the CB2 antagonist AM630, and it is devoid of activity at μ, δ and κ opioid receptors. The authors stress that it binds fewer biological targets than cannabidiol.","binding":[{"target":"GPR55","efficacy":"antagonist","relativeActivity":75,"reported":"antagoniste sans activité agoniste dans un essai β-arrestine sur GPR55 humain (Brenneman et coll., 2022)","confidence":"medium"},{"target":"Échangeur Na+/Ca2+ mitochondrial (mNCX)","efficacy":"modulator","relativeActivity":45,"reported":"neuroprotection abolie par l'inhibiteur CGP-37157 (Brenneman et coll., 2018)","confidence":"medium"}],"references":[{"label":"Kinney et coll., découverte du KLS-13019, agent neuroprotecteur dérivé du cannabidiol, de puissance, sécurité et perméabilité améliorées, ACS Medicinal Chemistry Letters 2016","pmid":"27096053","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/27096053/"},{"label":"Brenneman et coll., comparaisons pharmacologiques entre le cannabidiol et le KLS-13019, Journal of Molecular Neuroscience 2018","pmid":"30109468","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/30109468/"},{"label":"Foss et coll., effets comportementaux et pharmacologiques du cannabidiol et de son analogue KLS-13019 dans des modèles murins de douleur et de renforcement, British Journal of Pharmacology 2021","pmid":"33822373","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/33822373/"},{"label":"Brenneman et coll., propriétés anti-inflammatoires du KLS-13019, nouvel antagoniste de GPR55, sur cultures de ganglions de la racine dorsale et d'hippocampe, Journal of Molecular Neuroscience 2022","pmid":"35779192","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/35779192/"},{"label":"Ippolito et coll., le KLS-13019, analogue structural du cannabidiol et antagoniste de GPR55, prévient et inverse la neuropathie périphérique induite par la chimiothérapie chez le rat, Journal of Pharmacology and Experimental Therapeutics 2024","pmid":"39134424","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/39134424/"},{"label":"Légifrance, annexe IV de l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants","pmid":null,"doi":null,"url":"https://www.legifrance.gouv.fr/loda/article_lc/LEGIARTI000020689963/"},{"label":"PubChem CID 91824155 : KLS-13019 (identifiants)","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/91824155"}]},"pharmacokinetics":null,"metabolism":null,"detection":null,"subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":6},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":4},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":4},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":4},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":2}],"doseRanges":null,"humanDataCharacterised":false},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":true,"bannerTextFr":"Aucune dose humaine caractérisée : données animales / in vitro uniquement. Profil d'effet, marge de sécurité et toxicité aiguë non documentés en clinique humaine.","toxicologyFr":null},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":null,"reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"No control measure of its own at European Union level. The molecule appears in no schedule of the 1961 Convention on Narcotic Drugs or of the 1971 Convention on Psychotropic Substances. It holds no marketing authorisation and no novel food authorisation under Regulation (EU) 2015/2283: it circulates only as a chemical or reference standard intended for research.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Unscheduled substance. KLS-13019 is named in no annex of the order of 22 February 1990 and falls under no generic clause: it is not a tetrahydrocannabinol and it lacks the benzo[c]chromene nucleus targeted by the ANSM decision of 22 May 2024. This absence of scheduling is not an authorisation: the molecule is a drug candidate at the preclinical stage, with no marketing authorisation.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Kinney et coll., découverte du KLS-13019, agent neuroprotecteur dérivé du cannabidiol, de puissance, sécurité et perméabilité améliorées, ACS Medicinal Chemistry Letters 2016","pmid":"27096053","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/27096053/"},{"label":"Brenneman et coll., comparaisons pharmacologiques entre le cannabidiol et le KLS-13019, Journal of Molecular Neuroscience 2018","pmid":"30109468","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/30109468/"},{"label":"Foss et coll., effets comportementaux et pharmacologiques du cannabidiol et de son analogue KLS-13019 dans des modèles murins de douleur et de renforcement, British Journal of Pharmacology 2021","pmid":"33822373","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/33822373/"},{"label":"Brenneman et coll., propriétés anti-inflammatoires du KLS-13019, nouvel antagoniste de GPR55, sur cultures de ganglions de la racine dorsale et d'hippocampe, Journal of Molecular Neuroscience 2022","pmid":"35779192","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/35779192/"},{"label":"Ippolito et coll., le KLS-13019, analogue structural du cannabidiol et antagoniste de GPR55, prévient et inverse la neuropathie périphérique induite par la chimiothérapie chez le rat, Journal of Pharmacology and Experimental Therapeutics 2024","pmid":"39134424","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/39134424/"},{"label":"Légifrance, annexe IV de l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants","pmid":null,"doi":null,"url":"https://www.legifrance.gouv.fr/loda/article_lc/LEGIARTI000020689963/"},{"label":"PubChem CID 91824155 : KLS-13019 (identifiants)","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/91824155"}],"meta":{"slug":"kls-13019","url":"https://en.phytogrammes.com/wiki/kls-13019","lastVerified":"2026-05-01","dataUpdatedAt":"2026-10-11","confidence":"high","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}