Amyloid beta plaques, a hallmark of Alzheimer’s, induce neuroinflammation and astrogliosis. 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.
Alzheimer’s patients have higher serum levels of 2AG and PEA. In these patients, 2AG is positively correlated with cognitive performance suggesting therapeutic potential. PEA was inversely correlated with cognitive performance, underlining the differential characteristics of cannabinoids (Altamura et al., 2015).
Hippocampal Anandamide, OEA and PEA were increased after social exposure (Kerr et al., 2013) once more stipulating the involvement of the endocannabinoid system in autism.
Another 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. Several studies found that CB2 was upregulated with cystitis (Merriam et al., 2008; Tambaro et al., 2014) and that activation of CB2 with Anandamide or PEA attenuated pain and inflammation (Jaggar et al., 1998; Wang et al., 2013, 2014).
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.
Functional Gastro-Intestinal Disorders
In patients with diarrhea-type IBS higher levels of 2AG and lower levels of OEA and PEA were found. In contrast, patients with constipation-type IBS had higher levels of OEA and lower levels of FAAH. Also, PEA levels were inversely correlated with abdominal pain suggesting substantial involvement of the endocannabinoid system in the pathophysiology of IBS (Fichna et al., 2013).
cannabinoid receptors CB1 and CB2 are upregulated and Endocannabinoids like AEA, 2-AG, OEA and PEA show increased levels after cerebral ischemia (England et al., 2015; Lara-Celador et al., 2013).
In a mouse study, plant cannabinoid CBD and endocannabinoid PEA each individually reduced inflammation and neuronal demyelination (Rahimi et al., 2015).
In patients with Chronic Widespread pain, the endocannabinoid PEA was found to provide homeostatic pain control through the PPARα receptor (Ghafouri et al., 2013).
Similarly, systemic application of OEA, and to a lesser extent PEA, was found to inhibit pro-inflammatory cytokines and thus to protect against neurodegeneration (Sayd et al., 2014).
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