Role of palmitoylethanolamide (PEA) in depression: Translational evidence.
J Affect Disord. 2018 Oct 25. Epub 2018 Oct 25. PMID: 30391203
Danilo De Gregorio
BACKGROUND: Antidepressants have a low rate of response paired with a delayed onset of action. Translational studies are thus seeking for novel targets for antidepressant drug development. Preclinical evidence has demonstrated that the endocannabinoid system plays an important role in mood and stress response, even if drugs targeting this system have not yet become available for clinical use. The dietary supplement N-Palmitoylethanolamide (PEA) is a fatty acid amide belonging to the endocannabinoid system with potential antidepressant properties.
METHODS: We performed a bibliographic search to review current knowledge on the potential antidepressant effects of PEA and its underlying mechanism of action.
RESULTS: PEA targets not only the peroxisome proliferator-activated receptor-alpha (PPAR-α), but also the endocannabinoid system, binding the G-protein-coupled receptor 55, a non-CB/CBcannabinoid receptor, and also the CB/CBreceptors, although with a weak affinity. Preclinical studies have shown antidepressant activity of PEA in animal paradigms of depression and of depression associated with neuropathic pain and traumatic brain injury. In a translational perspective, PEA is increased in stress conditions, and a randomized, double-blind study in depressed patients indicated a fast-antidepressant action of PEA when associated with citalopram.
LIMITATIONS: There are still limited preclinical and clinical studies investigating the effect of PEA upon the endocannabinoid system and its potential as antidepressant.
CONCLUSIONS: PEA has potential antidepressant effects alone or in combinations with other classes of antidepressants. Future studies in depressed patients are needed to confirm the mood-modulating properties of PEA and its role as a biomarker of depression.