Written by Chrystal Moulton, Science Writer. Data from this trial suggests that PEATONIDE could significantly decrease disability, frequency, and intensity of migraine attacks in individuals with low frequency episodic migraine.

Migraines are chronic headaches which are moderate to severe in intensity and generally associated with sensitivity to light or sound. About 15% of the global population is affected by migraines¹. Migraine occurrence is categorized as either chronic [occurring 15 or more days per month over three months] or episodic [occurring less than 15 days per month]². Non-specific treatment to prevent migraines have a 67% failure rate³. However, drugs designed to prevent migraines are much more effective⁴. In the US, dietary supplementation is used by 40% of the population as an alternative therapy¹. Palmitoylethanolamide (PEA) is it compound known to regulate pain and inflammation^5,6. Melatonin, which regulates sleep, is also associated with neurological disorders including headaches⁷. In the current trial, researchers investigated the efficacy and tolerability of a patent treatment called PEATONIDE® (which is a combination of palmitoylethanolamide [PEA] and melatonin) in individuals suffering from migraine attacks².

This study was designed as a randomized, double-blind, placebo-control trial lasting 3 months. Men and women between the ages of 18 and 65 years old diagnosed with episodic migraine with or without aura were included in the study. Eligible participants had to have experienced episodic migraines at least one year prior to recruitment and at least two migrant attacks in the past three months. All volunteers were directed to maintain their usual lifestyle and dietary habits during the study. Two months prior to the start of the trial, participants were observed and data related to caffeine consumption, dietary habits, physical activity, as well as migraine frequency, intensity, and duration was collected from each participant. Volunteers completed headache diaries during the two months leading up to the official start of the trial and afterwards. At the start of the trial, participants were randomly assigned to receive the placebo or the treatment (PEATONIDE ®). They were required to take their assigned protocol once daily before bed for three months. PEATONIDE consists of 1200mg of PEA and 0.2mg of melatonin. The primary endpoint was a change in migraine frequency and secondary endpoints included change in intensity, duration, disability, symptoms, and use of analgesics associated with migraine attacks. Participants were allowed to use acetaminophen and NSAIDs as needed. No other preventative or acute treatments were allowed.

A total of 60 patients [30 women and 30 men] were found eligible for and completed this trial. The average age of patients was 42.5 ±10.5 years old. Participants in this trial were patients with low frequency episodic migraines [i.e. less than 8 migraine days per month] 27% of which experienced aura with their migraine episodes. No adverse events were reported during the clinical trial. Results from this trial showed the 27% of participants treated with PEATONIDE experienced >50% reduction in monthly migraine days [baseline: 3.4 ±0.5 v. T3: 2.2 ±0.4, P<0.001]. Also, patients in the treatment group experienced a significant decrease in migraine duration (P<0.01), intensity (P<0.001), disability (P<0.001), nausea and vomiting (P<0.001), and light/ sound sensitivity (P<0.05). No significant changes were observed in the placebo group. Furthermore, patients who originally experienced aura with migraine attacks after treatment with PEATONIDE no longer experienced aura after three months (P<0.001).

In all, data from this trial suggests that PEATONIDE could significantly decrease disability, frequency, and intensity of migraine attacks in individuals with low frequency episodic migraine. Additional studies will be needed to verify these findings.

Source: Piccolo, Vincenzo, Adua Marzocchi, Maria Maisto, Vincenzo Summa, Gian Carlo Tenore, and Angela Amoresano. “Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial.” Frontiers in Nutrition 12 (2025): 1560654.

© 2025 Piccolo, Marzocchi, Maisto, Summa, Tenore and Amoresano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 

Click here to read the full text study.

Posted August 12, 2025.

Chrystal is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Chicago.

References:

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2. Piccolo V, Marzocchi A, Maisto M, Summa V, Tenore GC, Amoresano A. Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial. Front Nutr. 2025;12:1560654. doi:10.3389/fnut.2025.1560654
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7. Ferrara P, Dell’Aquila L, Perrone G, et al. A Possible Pathogenic Linkage Among Headache, Migraine, and Nocturnal Enuresis in Children. Int Neurourol J. Dec 2016;20(4):311-315. doi:10.5213/inj.1632566.283