Journal
PHARMACOGENOMICS
Volume 18, Issue 2, Pages 143-156Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/pgs-2016-0147
Keywords
FAAH; fatty acid amide hydrolase; hypercapnic ventilatory response; morphine; opioid-cannabinoid interactions; postoperative; respiratory depression
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Funding
- Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH [5K23HD082782]
- National Center for Research Resources
- National Center for Advancing Translational Sciences, NIH [8 UL1 TR000077]
- APSF/ASA Safety Scientist Career Development Award by the Anesthesia Patient Safety Foundation
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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.
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