Many patients with chronic pain feel increasingly despondent. They feel chronically, depressed, irritated and tense, which is very logical. An American professor and his research team mapped out how this is related on the level of the nervous system and the brain. The researchers also found that the natural pain relief palmitoylethanolamide (PEA) doesn’t only reduce chronic pain, but can also improve the related negative feelings. [1]

Patients treated with PEA for chronic pain often notice they feel better and more positive after several days or weeks only. They feel more confident in handling things and are less irritable. We now understand how that works from a biological point of view. The schedule below shows a summary of this. We can see how damage to a nerve, for example related to hernia, diabetes or an accident, can cause a metabolic change in the brain. The positive and recovering effect of the palmitoylethanolamide supplement is shown in the tables within the schedule. The entire article is freely available online (click on the reference).


Dysfunction in biological factors with chronic pain and depression

Professor di Marzo’s team researched numerous of biological factors in the brain that are responsible for maintaining chronic pain and several factors that play a role in depression and negative moods. It turns out that both chronic pain and depressed feelings stay present due to several metabolic dysfunctions and that the body tries to compensate by increasing the palmitoylethanolamide levels to protect cells and decrease inflammation. The fact that PEA plays an important role here is something that other researchers had noticed as well. They found that anti-depressants like imipramine, escitalopram and tianeptine could increase the PEA levels in the brain [2].  These types of anti-depressants often have many side effects causing many patients to quit.  It would be more convenient to start using the natural substance PEA immediately. This idea is being supported by the work of di Marzo, who found that PEA indeed has anti- depressant properties on depressed symptoms. The effect turns out to be even better than that of Fluoxetine, as other researchers have claimed [3].

After giving more PEA, Di Marzo and colleagues  found that the self-regulating pain decreased and the anti-depressant effects still increased even further. Both the metabolic dysfunction in the brain as the pain and depression symptoms decreased significantly after treatment with PEA.



[1] Guida F1, Luongo L1, Marmo F2, Romano R1, Iannotta M1, Napolitano F3, Belardo C1, Marabese I1, D’Aniello A4, De Gregorio D1, Rossi F5, Piscitelli F6, Lattanzi R7, de Bartolomeis A2, Usiello A3, Di Marzo V6, de Novellis V1, Maione S8. | Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice. | Mol Brain. | 2015 Aug 12;8(1):47. doi: 10.1186/s13041-015-0139-5.

[2] Smaga I1, Bystrowska B, Gawli?ski D, Pomierny B, Stankowicz P, Filip M. | Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures. | Neurotox Res. | 2014 Aug;26(2):190-206. doi: 10.1007/s12640-014-9465-0. Epub 2014 Mar 21.

[3] Yu HL, Deng XQ, Li YJ, Li YC, Quan ZS, Sun XY. | N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice. |Pharmacol Rep. | 2011 May-Jun;63(3):834-9.