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N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance

Mauro Congiu, Laura Micheli, Michele Santoni, Claudia Sagheddu, Anna Lisa Muntoni, Alexandros Makriyannis, Michael S Malamas, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Marco Pistis. Neurotherapeutics. 2021 Oct;18(4):2722-2736.

Laboratory studyOther animalsWith AM11095 (a brain-permeable NAAA inhibitor that raises the body's own palmitoylethanolamide) given with morphine; PEA itself was not given

This study tested palmitoylethanolamide together with AM11095 (a brain-permeable NAAA inhibitor that raises the body's own palmitoylethanolamide) given with morphine; PEA itself was not given. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
Rats; numbers not stated in the abstract
Dose used in the study
AM11095 at 3 to 30 mg/kg with morphine; route not stated in the abstract
Duration
Chronic morphine treatment; length not stated in the abstract
What was measured
Mechanical pain threshold; in vivo electrophysiology of locus coeruleus neurons in anaesthetised rats; spinal cord glial activation.

What the authors reported

The study found:

  • AM11095 dose-dependently enhanced morphine's pain-relieving effect and delayed the development of tolerance to chronic morphine.
  • It enhanced morphine's dampening of locus coeruleus responses to foot-shock and prevented loss of that effect with chronic use.
  • These changes went with less glial activation in the spinal cord.

Limits of this study

A rat study; it cannot show effect in people. No palmitoylethanolamide was given; the inhibitor raised the body's own PEA. The authors declare no competing interests.

Source

PubMed 34553321 · doi:10.1007/s13311-021-01116-4

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.