{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"HAQNKTBQOIAWDB-DNQXCXABSA-N","prefName":"SP-111 (Δ9-THC morpholinylbutyrate)","symbol":"SP-111","iupacName":"[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-yl] 4-morpholin-4-ylbutanoate","aliases":["SP-111","SP-111A","THC morpholinylbutyrate","morpholinylbutyrate de tétrahydrocannabinol"],"cas":"55602-38-5","pubchemCid":"6453212","chebiId":null,"smiles":"CCCCCC1=CC2=C([C@@H]3C=C(CC[C@H]3C(O2)(C)C)C)C(=C1)OC(=O)CCCN4CCOCC4","molecularFormula":"C29H43NO4","molecularWeight":469.7,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/6453212"}},"classification":{"family":"semisynthetique","familyLabel":"Semi-synthetic cannabinoid","origin":"semisynthetic","originLabel":"Semi-synthétique","structuralClassFr":"Ester aminé du Δ9-THC. Le squelette benzo[c]chromène et sa chaîne pentyle sont conservés ; la fonction phénol porte un ester dont la chaîne se termine par un cycle morpholine. C'est une stratégie classique de solubilisation : greffer une amine ionisable sur une molécule lipophile par un lien clivable, de sorte que le sel soit soluble et que l'hydrolyse restitue la molécule d'origine. La lenteur de cette hydrolyse est précisément ce qui a limité le composé."},"originSynthesis":{"heading":"Route of preparation (chemical process)","summaryFr":"No plant route. SP-111 is an ester of Δ9-THC: the phenol function at position 1 of the benzo[c]chromene skeleton is esterified by 4-(morpholin-4-yl)butanoic acid. The tertiary nitrogen of the morpholine ring, which can be protonated, is the element that confers water solubility in salt form. It is described here by chemical class only.","originNote":"A semi-synthetic compound, absent from cannabis. It is obtained by esterification of the phenol of Δ9-THC with a butanoic acid bearing a morpholine ring, whose basic nitrogen allows the formation of water-soluble salts. It never left the field of research.","discovered":"Mis au point dans les années 1970, le SP-111 compte parmi les premiers dérivés du THC capables de former des sels hydrosolubles, ce qui constituait alors un progrès considérable : le THC est pratiquement insoluble dans l'eau, obstacle majeur pour l'administration parentérale dans la recherche animale. Ses effets sur l'activité neuronale du cerveau de rat ont été publiés par Segal en 1978 dans Brain Research."},"pharmacology":{"summaryFr":"SP-111 is a water-soluble prodrug of Δ9-THC, obtained by esterification of the phenol with a butanoic acid bearing a morpholine ring. It answers a practical obstacle that long held back cannabinoid research: THC is almost insoluble in water, which rules out simple injectable formulations and requires oily or detergent vehicles whose own effects blur the interpretation of experiments. The basic nitrogen of the morpholine allows soluble salts to be formed and lifts that constraint. Segal published in 1978 in Brain Research a study of its effects on neuronal activity in the rat brain. The compound did not, however, live up to its promise: conversion to THC is slow and variable, which gives poorly predictable pharmacokinetics and a potency lower than that of the parent molecule. Those limits explain why it remained a historical landmark of cannabinoid prodrug chemistry rather than a lastingly adopted tool.","receptorSummaryFr":"A prodrug of Δ9-THC: the observed activity results from the release of the parent molecule, a partial agonist of CB1 and CB2 receptors, and not from an interaction of the ester itself. Metabolic conversion to THC is, however, slow and variable, which makes the relationship between administered dose and effect less predictable than with THC itself and limits the compound's interest as an experimental tool.","binding":[{"target":"CB1","efficacy":"partial_agonist","relativeActivity":55,"reported":null,"confidence":"low"},{"target":"CB2","efficacy":"partial_agonist","relativeActivity":45,"reported":null,"confidence":"low"}],"references":[{"label":"Segal 1978 : effets du SP-111, dérivé hydrosoluble du THC, sur l'activité neuronale chez le rat","pmid":"624059","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/624059/"},{"label":"PubChem CID 6453212 : SP-111, identifiants et propriétés","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/6453212"}]},"pharmacokinetics":"L'intérêt annoncé était l'administration parentérale rendue possible par l'hydrosolubilité des sels. La conversion en Δ9-THC s'est révélée lente et variable, ce qui produit une pharmacocinétique imprévisible et une puissance apparente inférieure à celle du THC. Aucune donnée de pharmacocinétique humaine n'est publiée : les travaux disponibles portent sur le rongeur.","metabolism":"L'étape déterminante est l'hydrolyse enzymatique de la liaison ester, qui libère le Δ9-THC et l'acide morpholinylbutanoïque. Le devenir ultérieur est celui du THC : hydroxylation en position 11, oxydation en acide carboxylique, glucuronidation. La lenteur de la première étape fait que le composé se comporte comme un réservoir à libération prolongée mal contrôlée plutôt que comme un promédicament efficace.","detection":"Le composé n'est pas recherché en toxicologie de routine. Une exposition se documenterait par le dosage du Δ9-THC et de ses métabolites plutôt que par celui de l'ester, dont la persistance plasmatique n'a pas été caractérisée. Aucun immunoessai courant ne le détecte.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":40},{"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":60},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":55}],"doseRanges":null,"humanDataCharacterised":true},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":false,"bannerTextFr":null,"toxicologyFr":"Aucune donnée de toxicologie humaine : le composé n'a pas été administré à l'humain dans un cadre publié et ne circule pas comme produit de consommation. Le risque théorique est celui du THC libéré, avec la difficulté supplémentaire que représente une libération lente et irrégulière, laquelle rend la relation dose-effet peu prévisible."},"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. SP-111 has never been the subject of a marketing authorisation application 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: SP-111, an ester of Δ9-THC, falls directly under that heading, as do its water-soluble 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":"Segal 1978 : effets du SP-111, dérivé hydrosoluble du THC, sur l'activité neuronale chez le rat","pmid":"624059","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/624059/"},{"label":"PubChem CID 6453212 : SP-111, identifiants et propriétés","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/6453212"}],"meta":{"slug":"sp-111","url":"https://en.phytogrammes.com/wiki/sp-111","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."}}