Opioid effects are potentiated by
cannabinoid agonists including
anandamide, an
endocannabinoid. Inter-individual variability in responses to
opioids is a major clinical problem. Multiple deaths and anoxic
brain injuries occur every year because of
opioid-induced
respiratory depression (RD) in surgical patients and drug abusers of
opioids and
cannabinoids. This study aimed to determine specific associations between genetic variants of
fatty acid amide hydrolase (FAAH) and postoperative central
opioid adverse effects in children undergoing
tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard
perioperative care with a standard
anesthetic and an intraoperative dose of
morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative
opioid adverse effects including, RD,
postoperative nausea and vomiting (
PONV) and prolonged stay in Post
Anesthesia Recovery Room (postoperative
anesthesia care unit, PACU) due to RD and
PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory
PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing
tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with
PONV and RD in our cohort; association between
PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory
PONV,
opioid-related RD, and prolonged PACU stay due to
opioid adverse effects in white children undergoing
tonsillectomy.