The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels
Laboratory studyHumansDogsOther animals
- Design
- Laboratory study
- Subjects
- Human keratinocyte cultures; Ascaris-hypersensitive beagle dogs given a single oral dose; healthy human volunteers given a single oral dose; HEK-293 cells expressing TRPV1
- Dose used in the study
- Dogs: ultramicronised PEA 30 mg/kg once. Volunteers: micronised PEA 300 mg once. Cells: 10 to 20 micromolar
- Duration
- Blood sampled over 8 hours in dogs and 6 hours in people
- What was measured
- Plasma and cell levels of 2-arachidonoylglycerol (2-AG) by mass spectrometry; calcium responses of TRPV1-expressing cells
What the authors reported
Oral PEA raised plasma 2-AG about 2-fold in people and about 20-fold in dogs, and 3-fold in keratinocytes. 2-AG raised calcium in TRPV1-expressing cells and desensitised them to capsaicin. PEA only slightly enhanced 2-AG activation of TRPV1 but significantly increased the 2-AG-induced desensitisation. The authors say this may explain why several effects of PEA are attenuated by cannabinoid receptor or TRPV1 antagonists.
Limits of this study
A mechanism study with small numbers, mostly in cells; the human and dog arms measured a blood marker after one dose, not a clinical effect. Three authors list Epitech Group as an affiliation. The entourage effect is a hypothesis this paper supports, not a demonstrated clinical mechanism.
Source
PubMed 25598150 · doi:10.1111/bph.13084
Entry checked against the abstract on PubMed on 2026-10-19. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.