{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"PXBRWSCGFNNIKS-IAGOWNOFSA-N","prefName":"Δ9-tetrahydrocannabinol phosphate","symbol":"THC-O-phosphate","iupacName":"[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-yl] dihydrogen phosphate","aliases":["THC-O-phosphate","phosphate de THC","THC phosphate ester","Δ9-THC-O-phosphate"],"cas":null,"pubchemCid":"9865413","chebiId":null,"smiles":"CCCCCc1cc2c(c(OP(=O)(O)O)c1)[C@@H]1C=C(C)CC[C@H]1C(C)(C)O2","molecularFormula":"C21H31O5P","molecularWeight":394.4,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/9865413"}},"classification":{"family":"semisynthetique","familyLabel":"Semi-synthetic cannabinoid","origin":"semisynthetic","originLabel":"Semi-synthétique","structuralClassFr":"Ester phosphorique du tétrahydrocannabinol. Le squelette benzo[c]chromène, la chaîne pentyle et la stéréochimie 6aR,10aR sont conservés ; seule la fonction phénol porte le groupement phosphate. Cette classe de promédicaments fonctionne bien quand une phosphatase clive efficacement l'ester, comme dans le cas de la psilocybine ; ici, la résistance du phénol encombré à l'action des phosphatases fait échouer le mécanisme."},"originSynthesis":{"heading":"Route of preparation (chemical process)","summaryFr":"No plant route. The compound is the phosphoric ester of Δ9-THC: the phenol function at position 1 of the benzo[c]chromene skeleton bears a dihydrogen phosphate group. It is that group, ionised at physiological pH, which confers water solubility. The molecule is described here by chemical class only.","originNote":"A semi-synthetic compound, absent from cannabis. It results from phosphorylation of the phenol of tetrahydrocannabinol, an operation that introduces a strongly ionisable and therefore water-soluble group. It has no commercial existence and belongs to the field of research.","discovered":"L'approche remonte à 1978, quand Yoshimura, Watanabe, Oguri, Fujiwara et Ueki publient dans le Journal of Medicinal Chemistry la synthèse et l'évaluation pharmacologique d'un ester phosphate de tétrahydrocannabinol. L'objectif était le même que pour les autres promédicaments de l'époque : obtenir une forme hydrosoluble d'un composé qui ne l'est pas, afin de pouvoir l'injecter dans les protocoles de recherche animale. Une précision s'impose sur la lecture de cette fiche : les travaux de 1978 portaient sur l'ester du Δ8-THC, isomère moins actif mais plus stable, tandis que la présente entrée décrit l'ester du Δ9-THC, dont le même schéma réactionnel permet l'obtention."},"pharmacology":{"summaryFr":"Tetrahydrocannabinol phosphate is a water-soluble prodrug obtained by phosphorylation of the phenol of THC, on the model of psilocybin, itself the phosphoric ester of an active compound. The analogy stops at the structure, however. Yoshimura and colleagues (1978), who carried out that work on the ester of Δ8-THC, found that the phosphate hydrolyses only with difficulty, both by alkaline phosphatase and by a mouse liver homogenate, which compromises the very principle of the prodrug. The pharmacological profile bears the trace of this: the cataleptogenic effect and the potentiation of thiopental sleep in mice represented only about ten and seven per cent of those of Δ8-THC, while the hypothermic effect retained comparable potency with a longer duration. Acute toxicity was by contrast far lower than that of the parent compound. The present entry describes the ester of Δ9-THC, obtained by the same scheme; the pharmacological data cited come from the Δ8 series and are transposable to it only with caution.","receptorSummaryFr":"A prodrug: the expected activity is that of the tetrahydrocannabinol released by hydrolysis, a partial agonist of CB1 and CB2 receptors. The weak point of the concept was established from the outset: the phosphate ester of Δ8-THC hydrolyses only with difficulty, both under the action of alkaline phosphatase and of a mouse liver homogenate. That poor release explains the observed profile, in which the cataleptogenic and sleep-potentiating effects represented only about ten and seven per cent of those of Δ8-THC.","binding":[{"target":"CB1","efficacy":"partial_agonist","relativeActivity":35,"reported":null,"confidence":"low"},{"target":"CB2","efficacy":"partial_agonist","relativeActivity":30,"reported":null,"confidence":"low"}],"references":[{"label":"Yoshimura et coll. 1978 : synthèse et activité pharmacologique d'un ester phosphate du Δ8-THC","pmid":"569207","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/569207/"},{"label":"PubChem CID 9865413 : ester phosphorique du tétrahydrocannabinol","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/9865413"}]},"pharmacokinetics":"Le composé a été conçu pour l'administration parentérale que permet son hydrosolubilité. Sa cinétique est dominée par la lenteur de l'hydrolyse : l'ester du Δ8-THC résiste à la phosphatase alcaline comme à l'homogénat hépatique de souris in vitro, ce qui se traduit in vivo par une puissance amoindrie sur les effets rapides et par un allongement de la durée de l'effet hypothermique. Aucune donnée humaine n'existe.","metabolism":"L'étape limitante est la déphosphorylation, qui devrait libérer le tétrahydrocannabinol mais s'accomplit mal. La fraction effectivement hydrolysée suit ensuite le métabolisme du THC : hydroxylation en position 11, oxydation en acide 11-nor-9-carboxylique, glucuronidation. La faible efficacité de la première étape explique que le composé se comporte davantage comme une molécule propre, peu active, que comme une réserve de THC.","detection":"Non recherché en toxicologie de routine. Sa mise en évidence supposerait une méthode ciblée par chromatographie liquide couplée à la spectrométrie de masse, le groupement phosphate rendant la molécule fortement polaire et donc mal adaptée aux méthodes conçues pour les cannabinoïdes neutres. Une exposition se traduirait aussi par la présence de THC et de ses métabolites usuels.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":35},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":15},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":55},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":40},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":30}],"doseRanges":null,"humanDataCharacterised":true},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":false,"bannerTextFr":null,"toxicologyFr":"La toxicité aiguë mesurée chez la souris était bien inférieure à celle du Δ8-THC, conséquence attendue d'une libération incomplète du principe actif. Aucune donnée humaine n'existe et le composé ne circule pas comme produit de consommation. Il ne doit pas être confondu avec le THC-O-acétate, ester acétique dont la pyrolyse produit du cétène et qui pose, lui, un problème de sécurité respiratoire documenté."},"legal":{"scheduleStatus":"controlled-clause","scheduleLabel":"Narcotic: generic clause","frScheduleStatus":"controlled-clause","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":"Tetrahydrocannabinol and its esters fall under the national control ensured by Member States pursuant to the convention of 1971. The compound has never been the subject of a marketing authorisation or of a specific European measure.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"A narcotic. Annex IV of the arrêté of 22 February 1990 classifies as narcotics the tetrahydrocannabinols, their esters, their ethers and their salts, as well as the salts of those derivatives. The phosphoric ester of THC falls under that heading, as do its salts.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Yoshimura et coll. 1978 : synthèse et activité pharmacologique d'un ester phosphate du Δ8-THC","pmid":"569207","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/569207/"},{"label":"PubChem CID 9865413 : ester phosphorique du tétrahydrocannabinol","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/9865413"}],"meta":{"slug":"thc-o-phosphate","url":"https://en.phytogrammes.com/wiki/thc-o-phosphate","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-14","confidence":"medium","dataCompletenessPct":80,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}