ArticleThe Journal of pharmacology and experimental therapeutics2008
The endocannabinoid anandamide is a substrate for the human polymorphic cytochrome P450 2D6.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The trial behind it
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Who cites it
40 citing papers in PubMed, 103 citations in OpenAlex.
- Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament.PloS one · 2014Trial
- Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort.Breast cancer research and treatment · 2009Trial
- Endogenous biomarkers for assessing CYP3A4 and CYP2D6 activity: A critical review.Drug metabolism and disposition: the biological fate of chemicals · 2026Review
- Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2025Review
- Network-based drug repurposing for psychiatric disorders using single-cell genomics.Cell genomics · 2025Article
- The Hunt for the Putative Epoxyeicosatrienoic Acid Receptor.ACS chemical biology · 2025Review
- Review
- The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics.Frontiers in pharmacology · 2022Article
- Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.British journal of pharmacology · 2021Article
- Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach.Toxics · 2021Review
- Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism.Pharmaceutics · 2021Review
- The rise and fall of anandamide: processes that control synthesis, degradation, and storage.Molecular and cellular biochemistry · 2021Review
- Cannabidiol and Neurodevelopmental Disorders in Children.Frontiers in psychiatry · 2021Review
- CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.Pharmacology & therapeutics · 2020Review
- Pathophysiological implications of neurovascular P450 in brain disorders.Drug discovery today · 2016Review
- Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs.Dialogues in clinical neuroscience · 2016Review
- Metabolism of Anandamide by Human Cytochrome P450 2J2 in the Reconstituted System and Human Intestinal Microsomes.The Journal of pharmacology and experimental therapeutics · 2016Article
- Anandamide and its metabolites: what are their roles in the kidney?Frontiers in bioscience (Scholar edition) · 2016Review
- Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive.Pharmacological research · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Members of the cytochrome P450 (P450) family of drug-metabolizing enzymes are present in the human brain, and they may have important roles in the oxidation of endogenous substrates. The polymorphic CYP2D6 is one of the major brain P450 isoforms and has been implicated in neurodegeneration, psychosis, schizophrenia, and personality traits. The objective of this study was to determine whether the endocannabinoid arachidonoylethanolamide (anandamide) is a substrate for CYP2D6. Anandamide is the endogenous ligand to the cannabinoid receptor CB1, which is also activated by the main psychoactive component in marijuana. Signaling via the CB1 receptor alters sensory and motor function, cognition, and emotion. Recombinant CYP2D6 converted anandamide to 20-hydroxyeicosatetraenoic acid ethanolamide and 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EET-EAs) with low micromolar K(m) values. CYP2D6 further metabolized the epoxides of anandamide to form novel dioxygenated derivatives. Human brain microsomal and mitochondrial preparations metabolized anandamide to form hydroxylated and epoxygenated products, respectively. An inhibitory antibody against CYP2D6 significantly decreased the mitochondrial formation of the EET-EAs. To our knowledge, anandamide and its epoxides are the first eicosanoid-like molecules to be identified as CYP2D6 substrates. Our study suggests that anandamide may be a physiological substrate for brain mitochondrial CYP2D6, implicating this polymorphic enzyme as a potential component of the endocannabinoid system in the brain. This study also offers support to the hypothesis that neuropsychiatric phenotype differences among individuals with genetic variations in CYP2D6 could be ascribable to interactions of this enzyme with endogenous substrates.
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What OpenQuestion holds
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.