Alzheimer´s

Endogenous PEA levels rise with astrogliosis. PEA, in turn, blocks pro-inflammatory cytokines through PPARα (Scuderi et al., 2011). This suggests that the PEA-PPARα interaction functions to curtail neuroinflammation and inhibit the progression of Alzheimer’s.

Autism

In a rat model of Autism (Valproic Acid model), GPR55, PPARα and PPARγ were reduced in several brain regions involved in higher cognitive functions (frontal cortex and hippocampus) (Kerr et al., 2013)

bulimia

OEA reduced food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006).

Cystitis

A rat study found that endocannabinoid PEA and CB1 were upregulated, PPARα was downregulated and CB2 was unchanged upon induction of Cystitis (Pessina et al., 2014). PEA attenuated pain and bladder voiding. This effect was blocked by CB1 and PPARα antagonists.

Eczema

In an experimental mouse model of Eczema endocannabinoids AEA and PEA were increased and TRPV1 and PPARα were upregulated (Petrosino et al., 2010). PEA enhances AEA activity at CB1, CB2 and TRPV1 receptors and protects against keratinocyte inflammation in a TRPV1-, but not CB1, CB2 or PPARα-dependent way.

Huntington's

A meta-analysis of human and rodent genetics studies found consistent changes in CB1, PPARα and NAPE-PLD in patients and animal models of Huntington’s Disease (Laprairie et al., 2015), suggesting involvement of the endocannabinoid system.

obesity

OEA reduced food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006).

pain

In patients with Chronic Widespread pain, the endocannabinoid PEA was found to provide homeostatic pain control through the PPARα receptor (Ghafouri et al., 2013).

Parkinson´s

In a mouse model of Parkinson’s, OEA (at 5mg/kg) protected dopaminergic neurons from degeneration in a PPARα-dependent way (Gonzalez-Aparicio et al., 2014).

References:

Ghafouri, N., Ghafouri, B., Larsson, B., Stensson, N., Fowler, C.J., and Gerdle, B. (2013). Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity. pain 154, 1649–1658.

Gonzalez-Aparicio, R., Blanco, E., Serrano, A., Pavon, F.J., Parsons, L.H., Maldonado, R., Robledo, P., Fernandez-Espejo, E., and de Fonseca, F.R. (2014). The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol. CINP 17, 455–468.

Kerr, D.M., Downey, L., Conboy, M., Finn, D.P., and Roche, M. (2013). Alterations in the endocannabinoid system in the rat valproic acid model of Autism. Behav. Brain Res. 249, 124–132.

Laprairie, R. B., Bagher, A. M., Precious, S. V., & Denovan-Wright, E. M. (2015). Components of the endocannabinoid and dopamine systems are dysregulated in Huntington’s disease: analysis of publicly available microarray datasets. Pharmacology Research & Perspectives, 3(1). https://doi.org/10.1002/prp2.104

Overton, H.A., Babbs, A.J., Doel, S.M., Fyfe, M.C.T., Gardner, L.S., Griffin, G., Jackson, H.C., Procter, M.J., Rasamison, C.M., Tang-Christensen, M., et al. (2006). Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3, 167–175.

Pessina, F., Capasso, R., Borrelli, F., Aveta, T., Buono, L., Valacchi, G., Fiorenzani, P., Di Marzo, V., Orlando, P., and Izzo, A.A. (2014). Protective Effect of Palmitoylethanolamide in a Rat Model of Cystitis. J. Urol.

Petrosino, S., Cristino, L., Karsak, M., Gaffal, E., Ueda, N., Tüting, T., Bisogno, T., De Filippis, D., D’Amico, A., Saturnino, C., et al. (2010). Protective role of palmitoylethanolamide in contact allergic dermatitis. Allergy 65, 698–711.

Scuderi, C., Esposito, G., Blasio, A., Valenza, M., Arietti, P., Steardo, L., Carnuccio, R., De Filippis, D., Petrosino, S., Iuvone, T., et al. (2011). Palmitoylethanolamide counteracts reactive astrogliosis induced by β-amyloid peptide. J. Cell. Mol. Med. 15, 2664–2674.