ArticleDrug metabolism and disposition: the biological fate of chemicals2009
Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Pooled it
- A high-fat meal significantly impacts the bioavailability and biphasic absorption of cannabidiol (CBD) from a CBD-rich extract in men and women.Scientific reports · 2025Trial
- Pharmacogenetic Predictors of Cannabidiol Response and Tolerability in Treatment-Resistant Epilepsy.Clinical pharmacology and therapeutics · 2021Trial
- Trial
- Predicting Cannabidiol Pharmacokinetics in Older Adults Via Physiologically Based Pharmacokinetic Modeling.The AAPS journal · 2026Article
- Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.Biomolecules & therapeutics · 2026Article
- Characterization of the Formation of the Acyl Glucuronide Metabolite of 7-Carboxy-Cannabidiol in Human Liver, Kidney, and Intestinal Microsomes andACS medicinal chemistry letters · 2026Article
- Update of the statement on safety of cannabidiol as a novel food.EFSA journal. European Food Safety Authority · 2026Article
- Genotype-Specific Safety and Pharmacokinetics of Cannabidiol in Healthy Volunteers.Clinical and translational science · 2026Article
- Review
- NAD(P)Archives of toxicology · 2025Article
- UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Distinct Interactions of Cannabinol and Its Cytochrome P450-Generated Metabolites with Receptors and Sensory Neurons.Journal of medicinal chemistry · 2025Article
- Utilization of Cannabidiol in Post-Organ-Transplant Care.International journal of molecular sciences · 2025Review
- Physiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta-9-Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes.Clinical and translational science · 2025Article
- Article
- Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions.Pharmaceutics · 2024Review
- Cannabinoid-Induced Inhibition of Morphine Glucuronidation and the Potential for In Vivo Drug-Drug Interactions.Pharmaceutics · 2024Article
- Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review.Current pharmaceutical design · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive ingredient in marijuana, is subject to cytochrome P450 oxidation and subsequent UDP-glucuronosyltransferase (UGT)-dependent glucuronidation. Many studies have shown that CYP2C9 and CYP3A4 are the primary enzymes responsible for these cytochrome P450-dependent oxidations, but little work has been done to characterize phase II metabolic pathways. In this study, we test the hypothesis that there are specific human UGTs responsible for classic cannabinoid metabolism. The activities of 12 human recombinant UGTs toward classic cannabinoids [cannabinol (CBN), cannabidiol (CBD), (-)-Delta(8)-THC, (-)-Delta(9)-THC, (+/-)-11-hydroxy-Delta(9)-THC (THC-OH), and (-)-11-nor-9-carboxy-Delta(9)-THC (THC-COOH)] were evaluated using high-performance liquid chromatography-tandem mass spectrometry and labeling assays. Despite activity by UGT1A1, 1A3, 1A8, 1A9, 1A10, and 2B7 toward CBN, CBD, THC-OH, and THC-COOH, only selected UGTs demonstrate sufficient activity for further characterization of steady-state kinetics. CBN was the most recognized substrate as evidenced by activities from hepatic UGT1A9 and extrahepatic UGT1A7, UGT1A8, and UGT1A10. These results may reflect the introduction of an aromatic ring to Delta(9)-THC, leading to favorable pi stacking with phenylalanines in the UGT active site. Likewise, oxidation of Delta(9)-THC to THC-OH results in UGT1A9 and UGT1A10 activity toward the cannabinoid. Further oxidation to THC-COOH surprisingly leads to a loss in metabolism by UGT1A9 and UGT1A10, while creating a substrate recognized by UGT1A1 and UGT1A3. The resulting glucuronide of THC-COOH is the main metabolite found in urine, and thus these hepatic enzymes play a critical role in the metabolic clearance of cannabinoids. Taken together, glucuronidation of cannabinoids depends on upstream processing including enzymes such as CYP2C9 and CYP3A4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.