Metabolism of tetrahydrocannabinol (THC) (Homo sapiens)

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65, 6611663, 61171631ConjugationMALDOPhase II metabolismMALCO11-oxo-THCP450 2C9CYP2C98-Hydroxy-delta-9-THCTHC-COOH-glucuronideTHC8,11-dihydroxy-delta-9-THCP450 3A11-nor-9-carboxy-THC11-hydroxy-THCADH2, 4, 8, 9Phase I metabolism


Description

Pathway visualizing part of THC metabolism. Delta9-tetrahydrocannabinol (THC, also named delta1-tetrahydrocannabinol), is the primary hallucinogenic constituent of Cannabis sativa (plant) a.k.a. marijuana. Different parts of the plant contain varying concentrations of THC, with leaves containing <1% to 10% THC by weight, and hashish, a resin prepared from the flowering tops, containing approximately 15% THC.

This drug undergoes various transformation in the Phase I (mainly hepatic metabolism primarily by hydroxylation), after which several metabolites can be transformed via Phase II reactions (such as acyl glucuronidatization). THC possesses activity at benzodiazepine, opioid, and cannabinoid receptors and also exerts effects on prostaglandin synthesis, DNA, RNA, and protein metabolism. Furthermore, THC work on the two types of cannabinoid receptor that exist in the human body — CB1 and CB2 — and these receptors are the primary targets of endogenous cannabinoids (endocannabinoids). THC binds to both cannabinoid receptors. The CB1 receptor is mostly found in the brain, while the CB2 receptor is found in immune tissues such as the spleen, thymus, and tonsils (but not in the brain). Specific antagonists exist for each of the CB1 and CB2 receptors.

Cannabinoid-coupled G protein–coupled receptors are involved in the control of many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function.

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Bibliography

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  1. Maurer HH, Sauer C, Theobald DS; ''Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.''; Ther Drug Monit, 2006 PubMed Europe PMC Scholia
  2. Hanisch S, Paulke A, Toennes SW; ''11-nor-9-carboxy-delta-9-tetrahydrocannabinol glucuronide exhibits acyl-migration isomers.''; J Pharm Biomed Anal, 2017 PubMed Europe PMC Scholia
  3. Skopp G, Pötsch L; ''Stability of 11-nor-delta(9)-carboxy-tetrahydrocannabinol glucuronide in plasma and urine assessed by liquid chromatography-tandem mass spectrometry.''; Clin Chem, 2002 PubMed Europe PMC Scholia
  4. Kim JY, Kwon W, Kim HS, Suh S, In MK; ''Estimation of measurement uncertainty for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine using liquid chromatography-tandem mass spectrometry.''; J Anal Toxicol, 2014 PubMed Europe PMC Scholia
  5. Pichini S, Marchei E, Martello S, Gottardi M, Pellegrini M, Svaizer F, Lotti A, Chiarotti M, Pacifici R; ''Identification and quantification of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.''; Forensic Sci Int, 2015 PubMed Europe PMC Scholia
  6. Watanabe K, Matsunaga T, Kimura T, Funahashi T, Funae Y, Ohshima T, Yamamoto I; ''Major cytochrome P450 enzymes responsible for microsomal aldehyde oxygenation of 11-oxo-Delta8-tetrahydrocannabinol and 9-anthraldehyde in human liver.''; Drug Metab Pharmacokinet, 2002 PubMed Europe PMC Scholia
  7. Jenkins, AMANDA J., EDWARD J. Cone; ''Drug abuse handbook.''; CRC Press, 1998
  8. Regan SL, Maggs JL, Hammond TG, Lambert C, Williams DP, Park BK; ''Acyl glucuronides: the good, the bad and the ugly.''; Biopharm Drug Dispos, 2010 PubMed Europe PMC Scholia
  9. Huestis MA; ''Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol.''; Handb Exp Pharmacol, 2005 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
125300view17:36, 31 January 2023LarsgwAdd ISBN to reference
124805view21:37, 11 December 2022AlexanderPicofixed citations
124784view06:39, 11 December 2022AlexanderPicofixed citations
117157view09:46, 18 May 2021EweitzModified title
106782view13:26, 17 September 2019MaintBotHMDB identifier normalization
98304view05:13, 19 August 2018EgonwReplaced the DrugBank metabolite ID with a Wikidata ID with links.
98303view05:11, 19 August 2018EgonwRemoved duplicate fields in Biopax publicationXref.
95899view12:54, 2 February 2018DeSlModified description
95896view12:47, 2 February 2018DeSlOntology Term : 'phase I biotransformation pathway via cytochrome P450' added !
95895view12:46, 2 February 2018DeSlOntology Term : 'xenobiotic metabolic pathway' added !
95894view12:45, 2 February 2018DeSlChanged layout
95893view12:43, 2 February 2018DeSlAdded more literature refs, for metabolite I couldn't find an ID for
95892view12:21, 2 February 2018DeSlAdded new nodes, more literature references etc.
95853view17:31, 26 January 2018KhanspersOntology Term : 'drug pathway' added !
95852view17:29, 26 January 2018KhanspersModified description
95596view00:40, 7 January 2018MaintBotModified title
95203view15:36, 22 November 2017DeSlNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
11-hydroxy-THCMetabolite37482 (PubChem-compound)
11-nor-9-carboxy-THCMetabolite107885 (PubChem-compound)
11-oxo-THCMetabolite124158 (PubChem-compound)
8,11-dihydroxy-delta-9-THCMetaboliteQ55971997 (Wikidata)
8-Hydroxy-delta-9-THCMetaboliteHMDB0060910 (HMDB)
ADHProtein1.1.1.1 (Enzyme Nomenclature) alcohol dehydrogenase
CYP2C9ProteinENSG00000138109 (Ensembl)
P450 2C9ProteinP11712 (Uniprot-TrEMBL)
P450 3AProteinP08684 (Uniprot-TrEMBL)
THC-COOH-glucuronideMetabolite
  • Acyl glucuronidatised form
  • Name: 11-nor-ÃŽâ€�9-tetrahydrocannabinol-9-carboxylic acid glucuronide
THCMetabolite16078 (PubChem-compound) delta9-tetrahydrocannabinol

Annotated Interactions

No annotated interactions

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