PEA has demonstrated effectiveness for chronic pain of multiple types associated with many painful conditions, especially with neuropathic (nerve) pain, inflammatory pain and visceral pain such as endometriosis and interstitial cystitis.
Results. PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects.
Conclusions. In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions.
PEA directly activates CB2-like receptor or potentiates endocannabinoid actions. The latter, also referred to as the “entourage effect,” is achieved through enhancing the endogenous anandamide activity by increasing the affinity for receptors and/or through reducing the enzymatic degradation of anandamide and is thereby considered a cannabinoid system modulator. Table 2 shows the clinical studies published till date and their main results. . . The results are encouraging regarding the improvement of pelvic pain, as all the clinical studies showed a statistically significant improvement
how PEA works in the body. “It’s an endogenous fatty acid amide produced by the body in response to stressors, pain, and inflammation,” he said. “So it acts as a very good pain reliever for multiple types of pain and inflammation. It’s the body’s own anti-inflammatory and pain-control mechanism as a first responder.”
Not only that, he said, but it is produced throughout the body. “The uniqueness of PEA is that it’s an autacoid,” he said. “Autacoids are produced and used up locally in every tissue; it’s not just produced in one particular organ.” As a result, it’s produced where there is inflammation and pain in the body, he said.
He added that the ingredient is fast-acting (starts working within 15 minutes), and that its half-life is eight hours in the body; however, PEA’s effects are even longer lasting than that, he said. “It prevents the output of inflammatory cytokines and interleukins into your system, and because of this, the effects last longer because it acts on the on the symptoms,” he explained. “The half-life is eight hours in the body, but the effect you get happens throughout the day because it shuts off the of the inflammation and the of the pain.”
Results: PEA reduced pain in 16 (73%) of the 22 subjects, 11 subjects showed pain reduction of over 20%. Whilst both the responders and non-responders showed reductions in infra-slow oscillatory activity where orofacial nociceptor afferents terminate in the brainstem, only responders displayed reductions in the thalamus. Furthermore, functional connections between the brainstem and thalamus were altered only in responders.
Conclusion: PEA is effective at relieving NP. This reduction is coupled to a reduction in resting oscillations along the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission.
Interestingly, a recent case study found that in an individual without the ability to breakdown PEA, elevated serum PEA was associated with pain insensitivity, implying that endogenous PEA plays a role in pain processing.
The therapeutic efficacy of PEA has been tested in a multitude of indications related to inflammation and pain, and, in both animal models and clinical trials, PEA has proven to be safe and effective.27–35 This compound might become a promising new therapeutic possibility for CRPS, especially considering that its targets are nonneuronal cells: the mast cell and the glia cell.19,36 Both nonneuronal cells have been recognized since the last decade as important contributors to neuropathic pain and neuroinflammation.
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that, through modulation of mast cells and spinal glial cells activation on peripheral and central nervous system neurons, has been demonstrated to be effective on the different inflammatory mechanisms that develop and maintain both neurogenic and neuropathic pain
PEA . . . performs a great variety of biological functions related to chronic and neuropathic pain and inflammation, as has been demonstrated in clinical trials. These include peripheral neuropathies such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pains.
Conclusions: PEA was extremely efficacious on pain and function in a large cohort of patients with low back pain – sciatica.
PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy
Conclusions: This observational study provides evidence, albeit preliminary, for the efficacy and safety of um-PEA (Normast) as part of a multimodal therapeutic regimen in the treatment of pain-resistant patients
A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: . . Applied exogenously, PEA has proven efficacious in mast cell-mediated experimental models of acute and neurogenic inflammation. This fatty acid amide possesses also neuroprotective effects, . . These actions may be mediated by PEA acting through "receptor pleiotropism," i.e., both direct and indirect interactions of PEA with different receptor targets, e.g., cannabinoid CB2 and peroxisome proliferator-activated receptor-alpha.
In recent days, I have been experimenting with the Palmitoylethanolamide (PEA).
Intended Purpose: opioid tolerance reduction. While it is not in itself a cannabinoid, it does modulate cannabinoid receptors (CB1/CB2). It is well known that cannabinoids (CBD, THC, etc.) reverse opioid tolerance.
Results so far: opioid tolerance reduction this substance had provided me thus far has been superior to anything else I have ever tried, including the DLPA and Agmatine. It also boosts the effects of cannabinoids.
Negative Side effects: none thus far.