Palmitoylethanolamide, a natural painkiller without side effects

Palmitoylethanolamide, a natural painkiller without side effects


Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that is responsible for performing a diverse range of biological functions, which are related to chronic and neuropathic inflammation and pain as demonstrated in clinical trials. PEA acts by binding to the peroxisome receptor in the nucleus of a cell. A study conducted by Dutch researchers indicated that PEA could also be used as an effective painkiller, possibly due to the aspect of endogenous modulation. The study was published in the Journal of pain research. Moreover, the researchers have investigated that integration of PEA in treatment has no drug-drug interactions.


Sciatic Pain and Carpal Tunnel Syndrome

Researchers have not performed any clinical tests with palmitoylethanolamide, but they have facilitated significant clarity about the challenges and inaccessibility of the research. The emphasis of their analysis entails distinctive case studies in which the subjects have encountered pain as a result of blocked nerves, whereas the specific diagnoses of their condition reflected sciatic pain or the carpal tunnel syndrome.



The case studies collected by the researchers included a total of 1366 experimental subjects who were provided with the dose of palmitoylethanolamide. The lowest range of dose that subjects had received in these studies was 300 mg per day, while the highest range was noted as 1200 mg per day.


Figure 1: Structural presentation of Palmitoylethanolamide



The main aim of the Dutch researchers is to carry out an in-depth analysis of a study which was published by a team of Spanish researchers in 2010. The study of Guida et al. (2010) was never translated into English as a result of which, they fails to achieve international acclamation [1]. The Spanish researchers examined the effect of daily 600 mg dosage of palmitoylethanolamide causing pain reduction up to 70% in the experimental subjects.









Similarly, in the Italian research, the number need to treat (NNT) required PEA dosage of 600 mg per day to reduce the intensity of the pain. The result of the study illustrated that the NNT reduced to 1.5 after three weeks of PEA dosage administration. In other words, the Italians had to facilitate treatment to 1.5 subjects to reduce the pain intensity in 1 subject. The table above shows that PEA works better if the patient is treated for a significantly longer duration.











Side effects

The results of all the studies portrayed reduction in pain among most users, which is mainly due to the administration of palmitoylethanolamide. Moreover, the subjects have not complained about drowsiness or headaches. Thus events of side effects have not been reported.



The summary put forth by the Dutch researchers entails positive characteristics of palmitoylethanolamide, which are stated as follow:

  • Palmitoylethanolamide acts as a safe analgesic compound in nerve compression.
  • “The clinical use of palmitoylethanolamide in compression syndromes such as sciatic pain and carpal tunnel syndrome has been supported by its safety and efficacy profile.”
  • Palmitoylethanolamide is easy to administer.”
  • The number needed to treat of palmitoylethanolamide for sciatic pain to reach 50% pain reduction is 1.5 and the number needed to harm is at least in the hundreds, but for the time being not calculable due to the absence of serious and troublesome side effects leading to dropouts in clinical trials.”
  • “The risk–benefit balance of palmitoylethanolamide therefore favors its inclusion in the therapeutic armamentarium of chronic pain.”
  • Palmitoylethanolamide can be administered both as part of a multimodal therapy regime as well as a stand-alone analgesic.”



[1] Guida G, De Martino M, De Fabiani A, Cantieri L, Alexandre A, Vassallo GM, Rogai M, Lanaia F, Petrosino S. | La palmitoiletanolamida (Normast®) en el dolor neuropático crónico por lumbociatalgia de tipo compresivo: estudio clínico multicéntrico. Dolor. | Investigación Clínica & Terapéutica.|  2010; 25(1):35-42.