PEA shown to relieve severe headache faster than ibuprofen – Australia RCT

By Tingmin Koe

- Last updated on GMT

A man experiencing headache.  ©Getty Images
A man experiencing headache. ©Getty Images

Related tags palmitoylethanolamide headache RCT

The use of palmitoylethanolamide (PEA) has been shown to relieve severe headache faster than the pharmaceutical drug ibuprofen, according to a RCT conducted in Australia.

However, when it comes to mild and moderate headaches, ibuprofen – known to reduce tension headaches – was a better option for mild and moderate headaches.

Findings of the study were published in Food and Nutrition Sciences.

Said to be the first study to compare PEA to ibuprofen for headache, the trial aims to compare both in terms of reducing pain/severity and the duration of tension-type headaches.

The study was conducted by researchers from University of Queensland, RDC Clinical, Evidence Sciences, and Gencor Pacific Limited.

PEA is an endogenous fatty acid derivative expressed in body tissues, including the brain. It is produced on-demand from cell membranes as a protective response to noxious stimuli.

Research has shown that PEA is safe and well-tolerated when taken daily – from 300mg up to 1,200mg per day – for the management of chronic pain conditions. 

On the other hand, prolonged use of ibuprofen and aspirin, which are primarily treatment for headaches, has been shown to lead to adverse health outcomes, such as gastrointestinal upset and cardiovascular, renal, and hepatic effects.

Moreover, tolerance to some medications can also occur, which can in turn increase the incidence of medication overuse for headaches.

Study design

Conducted in Australia, the trial is a double-blind, randomised, single site, comparator controlled clinical study, involving 94 subjects between 18 and 71 who experienced at least two headache episodes per month.

The subjects were randomised to receive either PEA trademarked Levagen+ or ibuprofen.

Each 525mg dose of Levagen+ contained 450mg of PEA and about 75mg of LipiSperse – a bioavailability enhancement technology. The comparator used was 400mg of ibuprofen.

Upon headache onset, the subjects consumed the allocated product, recorded pain levels using a visual analogue scale (VAS) and recorded their pain scores at 30-minute intervals for up to four hours.


One of the key findings is that PEA acted faster than ibuprofen for resolving severe headaches.

Specifically, the mean amount of time taken for PEA to resolve severe headaches was 95.5 minutes and 116.9 minutes for ibuprofen.

“This result suggests PEA may be more effective against more severe headaches rather than mild or moderate headaches. It may therefore be that PEA may be a suitable for treating severe headaches and migraines rather than mild headache.

“Rescue medication use was significantly lower in the comparator group for total and moderate headache episodes. Therefore, the comparator, known to reduce tension headaches, may be a better option for mild and moderate headaches, while PEA may be better suited to more severe headaches,”​ said the researchers. 

Other than that, a comparable number of participants from the PEA and ibuprofen group recorded at least one headache, with 44 of them from the PEA group and 42 from the ibuprofen group.

In both groups, most headaches were reduced by two hours and almost all by four hours – 90 per cent in the PEA group and 97 per cent in the ibuprofen group.

The study, however, is without its shortcomings, as researchers pointed out that it relied on the subjects’ perception of headache severity. Therefore, the data collected could be influenced by the environmental and psychological factors that impact the individual’s pain threshold.


Source: Food and Nutrition Sciences

Efficacy of Palmitoylethanolamide (Levagen+) Compared to Ibuprofen for Reducing Headache Pain Severity and Duration in Healthy Adults: A Double-Blind, Parallel, Randomised Clinical Trial

DOI: 10.4236/fns.2022.137050​ 

Authors: Briskey, D. et al

Related news

Show more

Follow us


View more


Nutra Champions Podcast

Nutra Champions Podcast