Palmitoylethanolamide and hemp oil extract exert synergistic anti-nociceptive effects in mouse models of acute and chronic pain

Alex Mabou Tagne; Yannick Fotio; Lin Lin; Erica Squire; Faizy Ahmed; Tarif Ibne Rashid; Elnaz Karimian Azari; Daniele Piomelli

doi:10.1016/j.phrs.2021.105545

Palmitoylethanolamide and hemp oil extract exert synergistic anti-nociceptive effects in mouse models of acute and chronic pain

Pharmacol Res. 2021 May:167:105545. doi: 10.1016/j.phrs.2021.105545. Epub 2021 Mar 12.

Authors

Alex Mabou Tagne¹, Yannick Fotio¹, Lin Lin¹, Erica Squire¹, Faizy Ahmed¹, Tarif Ibne Rashid¹, Elnaz Karimian Azari², Daniele Piomelli³

Affiliations

¹ Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-4625, USA.
² Metagenics, Aliso Viejo, CA 92656, USA.
³ Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-4625, USA; Department of Biological Chemistry, University of California, Irvine, CA 92697-4625, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697-4625, USA. Electronic address: piomelli@hs.uci.edu.

PMID: 33722712
DOI: 10.1016/j.phrs.2021.105545

Abstract

The use of products derived from hemp - i.e., cannabis varieties with low Δ⁹-tetrahydrocannabinol (Δ⁹-THC) content - as self-medication for pain and other health conditions is gaining in popularity but preclinical and clinical evidence for their effectiveness remains very limited. In the present study, we assessed the efficacy of a full-spectrum hemp oil extract (HOE; 10, 50 and 100 mg-kg^-1; oral route), alone or in combination with the anti-inflammatory and analgesic agent palmitoylethanolamide (PEA; 10, 30, 100 and 300 mg-kg^-1; oral route), in the formalin and chronic constriction injury (CCI) tests. We found that HOE exerts modest antinociceptive effects when administered alone, whereas the combination of sub-effective oral doses of HOE and PEA produces a substantial greater-than-additive alleviation of pain-related behaviors. Transcription of interleukin (IL)-6 and IL-10 increased significantly in lumbar spinal cord tissue on day 7 after CCI surgery, an effect that was attenuated to the same extent by HOE alone or by the HOE/PEA combination. Pharmacokinetic experiments show that co-administration of HOE enhances and prolongs systemic exposure to PEA. Collectively, our studies lend support to possible beneficial effects of using HOE in combination with PEA to treat acute and chronic pain.

Keywords: Acute pain; Chronic pain; Hemp; Palmitoylethanolamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Pain / drug therapy*
Amides / therapeutic use*
Analgesics / therapeutic use*
Animals
Cannabis
Chronic Pain / drug therapy*
Disease Models, Animal
Drug Synergism
Ethanolamines / therapeutic use*
Male
Mice
Palmitic Acids / therapeutic use*
Plant Extracts / therapeutic use*

Substances

Amides
Analgesics
Ethanolamines
Palmitic Acids
Plant Extracts
hempseed oil
palmidrol