Inhibition of fatty acid amide hydrolase in the CNS prevents and reverses morphine tolerance in male and female mice
Laboratory studyOther animalsWith URB597 and URB937 (FAAH inhibitors, tested alone), with morphine
This study tested palmitoylethanolamide together with URB597 and URB937 (FAAH inhibitors, tested alone), with morphine. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.
- Design
- Laboratory study
- Subjects
- Male and female mice made tolerant to morphine, plus FAAH knockout mice (numbers not stated in the abstract)
- Dose used in the study
- URB597 1 and 3 mg/kg or URB937 3 mg/kg intraperitoneally daily 30 minutes before morphine; AM251 3 mg/kg, AM630 3 mg/kg or GW6471 4 mg/kg as antagonists
- Duration
- 7 days of twice-daily morphine
- What was measured
- Tail immersion nociceptive thresholds; spinal FAAH-regulated lipids by LC-MS/MS; spinal mRNA for NAPE-PLD, PPAR-alpha, CB1, CB2 and FAAH.
What the authors reported
This laboratory study found:
- URB597 prevented and reversed morphine tolerance in both sexes, as did genetic FAAH deletion, but the peripherally restricted URB937 did not.
- The CB2 antagonist AM630 blocked the effect, while AM251 and GW6471 weakened it.
- Spinal anandamide mobilisation rose in tolerant mice, with higher NAPE-PLD and PPAR-alpha mRNA.
Limits of this study
A mouse study; it cannot show effect in people. PEA was not given; the authors mention it as a FAAH substrate. Daniele Piomelli is an inventor on University of California patent applications for FAAH inhibitors.
Source
PubMed 32077093 · doi:10.1111/bph.15031
Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.