Metabolism of tetrahydrocannabinol (THC) (WP4174)

Homo sapiens

Open in new tab Open in NDEx
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads
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.

Authors

Denise Slenter , Kristina Hanspers , Egon Willighagen , Eric Weitz , Alex Pico , and Lars Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

xenobiotic metabolic pathway drug pathway phase I biotransformation pathway via cytochrome P450

Participants
Query Drugst.One

Label Type Compact URI Comment
8-Hydroxy-delta-9-THC Metabolite hmdb:HMDB0060910
8,11-dihydroxy-delta-9-THC Metabolite wikidata:Q55971997
11-oxo-THC Metabolite pubchem.compound:124158
11-nor-9-carboxy-THC Metabolite pubchem.compound:107885
11-hydroxy-THC Metabolite pubchem.compound:37482
THC Metabolite pubchem.compound:16078 delta9-tetrahydrocannabinol
P450 3A Protein uniprot:P08684
ADH Protein eccode:1.1.1.1 alcohol dehydrogenase
CYP2C9 Protein ensembl:ENSG00000138109
P450 2C9 Protein uniprot:P11712

References

  1. Drug Abuse Handbook [Internet]. Steven B. Karch F MD. CRC Press; 1997. 1152 p. Available from: https://books.google.com/books/about/Drug_Abuse_Handbook.html?hl=&id=N5JengEACAAJ OpenLibrary Worldcat
  2. Stability of 11-nor-delta(9)-carboxy-tetrahydrocannabinol glucuronide in plasma and urine assessed by liquid chromatography-tandem mass spectrometry. Skopp G, Pötsch L. Clin Chem. 2002 Feb;48(2):301–6. PubMed Europe PMC Scholia
  3. Major cytochrome P450 enzymes responsible for microsomal aldehyde oxygenation of 11-oxo-Delta8-tetrahydrocannabinol and 9-anthraldehyde in human liver. Watanabe K, Matsunaga T, Kimura T, Funahashi T, Funae Y, Ohshima T, et al. Drug Metab Pharmacokinet. 2002;17(6):516–21. PubMed Europe PMC Scholia
  4. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Huestis MA. Handb Exp Pharmacol. 2005;(168):657–90. PubMed Europe PMC Scholia
  5. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Maurer HH, Sauer C, Theobald DS. Ther Drug Monit. 2006 Jun;28(3):447–53. PubMed Europe PMC Scholia
  6. Acyl glucuronides: the good, the bad and the ugly. Regan SL, Maggs JL, Hammond TG, Lambert C, Williams DP, Park BK. Biopharm Drug Dispos. 2010 Oct;31(7):367–95. PubMed Europe PMC Scholia
  7. 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. Kim JY, Kwon W, Kim HS, Suh S, In MK. J Anal Toxicol. 2014 Apr;38(3):164–70. PubMed Europe PMC Scholia
  8. Identification and quantification of 11-nor-Δ9-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. Pichini S, Marchei E, Martello S, Gottardi M, Pellegrini M, Svaizer F, et al. Forensic Sci Int. 2015 Apr;249:47–51. PubMed Europe PMC Scholia
  9. 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide exhibits acyl-migration isomers. Hanisch S, Paulke A, Toennes SW. J Pharm Biomed Anal. 2017 Nov 30;146:261–5. PubMed Europe PMC Scholia