Vidya Chidambaran1,2, Valentina Pilipenko3, Kristie Spruance1, Raja Venkatasubramanian1, Jing Niu1,4, Tsuyoshi Fukuda2,4, Tomoyuki Mizuno4, Kejian Zhang3, Kenneth Kaufman5, Alexander A Vinks4, Lisa J Martin2,3, Senthilkumar Sadhasivam1,2. 1. Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA. 2. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA. 3. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. 4. Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. 5. Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Abstract
AIM: Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions. PATIENTS & METHODS: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. RESULTS: We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use. CONCLUSION: FAAH genotypes predict risk for morphine-related adverse outcomes.
AIM: Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions. PATIENTS & METHODS: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. RESULTS: We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use. CONCLUSION:FAAH genotypes predict risk for morphine-related adverse outcomes.
Authors: B F Cravatt; K Demarest; M P Patricelli; M H Bracey; D K Giang; B R Martin; A H Lichtman Journal: Proc Natl Acad Sci U S A Date: 2001-07-24 Impact factor: 11.205
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Authors: S Sadhasivam; X Zhang; V Chidambaran; J Mavi; V Pilipenko; T B Mersha; J Meller; K M Kaufman; L J Martin; J McAuliffe Journal: Pharmacogenomics J Date: 2015-01-06 Impact factor: 3.550
Authors: V Chidambaran; R Venkatasubramanian; X Zhang; L J Martin; J Niu; T Mizuno; T Fukuda; J Meller; A A Vinks; S Sadhasivam Journal: Pharmacogenomics J Date: 2016-01-26 Impact factor: 3.550