{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"DJTGGIYZQHHLGJ-RTBURBONSA-N","prefName":"O-2050","symbol":"O-2050","iupacName":"N-[6-[(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-3-yl]hex-4-ynyl]methanesulfonamide","aliases":["O 2050","O2050"],"cas":null,"pubchemCid":"16102146","chebiId":"92047","smiles":"CC1=CC[C@@H]2[C@@H](C1)C3=C(C=C(C=C3O)CC#CCCCNS(=O)(=O)C)OC2(C)C","molecularFormula":"C23H31NO4S","molecularWeight":417.197,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/16102146","chebi":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:92047"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Cannabinoïde tricyclique de type dibenzopyrane, apparenté au Δ8-THC par son noyau et distingué de lui par sa chaîne latérale. Là où le Δ8-THC porte une chaîne pentyle saturée, l'O-2050 porte une chaîne hexynyle dont la triple liaison rigidifie le segment et dont l'extrémité est coiffée d'un groupement méthanesulfonamide polaire. La chaîne latérale des cannabinoïdes est le déterminant classique de l'efficacité au récepteur CB1 : c'est en la modifiant que l'on passe d'un agoniste complet à un agoniste partiel, et la nature exactement intermédiaire du composé confirme cette règle plutôt qu'elle ne l'infirme."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The skeleton is that of a classical cannabinoid dibenzopyran, broadly identical to that of Δ8-THC, from which it differs by the replacement of the pentyl chain with a hexynyl chain capped by a methanesulfonamide group. It is this side-chain substitution, and not a modification of the tricyclic core, that was meant to produce the change in activity sought.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a pharmacology reagent and has never been the subject of clinical development.","discovered":"Analogue sulfonamide du Δ8-tétrahydrocannabinol, porteur d'une chaîne latérale acétylénique, proposé comme candidat au titre d'antagoniste neutre du récepteur CB1. Son profil complet a été publié en 2011 par Wiley et collaborateurs, à l'université du Commonwealth de Virginie, avec le concours des équipes de Pertwee à Aberdeen et de Huffman à Clemson. La conclusion de ce travail a contredit l'usage qui était fait du composé."},"pharmacology":{"summaryFr":"O-2050 illustrates a recurring problem in cannabinoid pharmacology: the difficulty of obtaining a genuinely neutral antagonist of the CB1 receptor. Rimonabant, the first reference antagonist, behaves at high concentration as an inverse agonist, meaning that it reduces the constitutive activity of the receptor in the absence of any agonist. That property blurs the interpretation of experiments and complicates the reading of adverse effects. Chemists therefore looked for molecules that simply occupy the site without closing it. O-2050, a sulfonamide analogue of Δ8-THC bearing an acetylenic chain, was one of the most widely used candidates for that purpose. Wiley and colleagues carried out its systematic evaluation in 2011 and the result is clear in both directions. In vitro the compound does behave as an antagonist: it displaces agonists and blocks their signal with no effect of its own. In vivo it does the opposite of what an antagonist is expected to do. It does not block agonists, even delivered directly into the brain, and it fully substitutes for Δ9-THC in mice trained to recognise that molecule, which is the behavioural signature of an agonist. The measurement of cyclic AMP signalling settles the matter: efficacy reaches about half that of a full agonist, the profile of a partial agonist. The authors conclude that the compound cannot be classified as a neutral antagonist. The consequence goes beyond the molecule itself: earlier work that had interpreted a reduction in food intake under O-2050 as proof of CB1 blockade rests on a false premise.","receptorSummaryFr":"The compound has good affinity for both CB1 and CB2 receptors. Its functional behaviour is, however, contradictory depending on the assay system. In vitro it antagonises cannabinoid agonists in labelled GTPγS binding assays and in the isolated mouse vas deferens, with no activity of its own in either system. In vivo it does not block the effects of agonists, even when given directly into the cerebral ventricles; it stimulates locomotor activity, it decreases food intake in the manner of rimonabant, and above all it fully substitutes for Δ9-THC in a drug discrimination procedure in mice, which is an agonist effect. Inhibition of forskolin-stimulated cyclic AMP production reaches about half the efficacy of the full agonist CP-55,940. Wiley and colleagues conclude that the compound is not a viable candidate for classification as a neutral CB1 antagonist.","binding":[{"target":"CB1","efficacy":"partial_agonist","relativeActivity":55,"reported":"Bonne affinité ; efficacité d'environ la moitié de celle du CP-55,940 sur l'AMP cyclique (Wiley et coll. 2011)","confidence":"medium"},{"target":"CB2","efficacy":"partial_agonist","relativeActivity":45,"reported":"Bonne affinité rapportée, sans caractérisation fonctionnelle détaillée","confidence":"medium"}],"references":[{"label":"Wiley et coll. 2011 : analyse structurale et pharmacologique de l'O-2050, prétendu antagoniste neutre du CB1","pmid":"21114999","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/21114999/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique publiée. Les travaux disponibles reposent sur des administrations par voie intraveineuse et intracérébroventriculaire chez la souris. Le fait que le composé produise des effets centraux après administration périphérique établit qu'il franchit la barrière hématoencéphalique, sans que sa cinétique ait été caractérisée. Aucune donnée humaine n'existe et aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée. Le noyau dibenzopyranique et le phénol libre en position 1 sont les sites classiquement pris en charge par les oxydations des cytochromes P450 et par la glucuronoconjugaison chez les cannabinoïdes apparentés, mais il s'agit d'une attente de classe et non d'un résultat mesuré pour ce composé.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Son dosage relève des méthodes de chromatographie liquide couplée à la spectrométrie de masse en tandem employées pour les cannabinoïdes de laboratoire.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":20},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":20},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":15},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":10},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":30}],"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":"Aucune donnée de toxicologie humaine n'est publiée et aucune dose humaine n'est caractérisée. Chez la souris, le composé stimule l'activité locomotrice, réduit la prise alimentaire et n'induit ni antinociception ni hypothermie aux doses étudiées, à la différence des autres analogues sulfonamides testés dans le même travail. Le risque principal que soulève ce composé est scientifique plutôt que sanitaire : son usage comme prétendu antagoniste neutre a produit des conclusions erronées dans la littérature."},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":"Non inscrit aux conventions de contrôle","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"Réactif de recherche ; non contrôlé","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Non inscrit ; usage de laboratoire uniquement","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Wiley et coll. 2011 : analyse structurale et pharmacologique de l'O-2050, prétendu antagoniste neutre du CB1","pmid":"21114999","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/21114999/"}],"meta":{"slug":"o-2050","url":"https://en.phytogrammes.com/wiki/o-2050","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-17","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}