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Palmitoylethanolamide, a natural painkiller with no side effects

Palmitoylethanolamide, a substance that the body makes itself and is also available as a supplement, may work as an anti-depressant. Human studies have shown that the same substance is also an effective pain killer, write Dutch researchers in the Journal of Pain.

Sciatica and carpal tunnel syndrome
The Dutch did not do experiments themselves with palmitoylethanolamide; instead they trawled up some obscure studies. They confined themselves to studies of subjects that suffered from pain caused by trapped nerves: they had sciatica or carpal tunnel syndrome.


In the trials that the Dutch researchers gathered, a total of 1366 subjects were given palmitoylethanolamide. In those studies, the lowest dose that the subjects got was 300 mg per day; the highest dose was 1200 mg per day.

Palmitoylethanolamide, a natural painkiller with no side effects

The Dutch focused on a study published by Spanish researchers in 2010, but which had never been translated into English and had therefore received little international attention. [Dolor. 2010;25(4):227-234.] In that study, a daily dose of 600 mg palmitoylethanolamide reduced the subjects' pain by seventy percent after 21 days.

Palmitoylethanolamide, a natural painkiller with no side effects

Palmitoylethanolamide, a natural painkiller with no side effects

In the Italian study they looked at, the number needed to treat to halve the pain at a dose of 600 mg per day went down to 1.5 after three weeks. That means that the Italians had to treat 1.5 people to halve the pain in one subject. The figure above shows that palmitoylethanolamide works better the longer it is administered for.

Side effects
In all the studies, palmitoylethanolamide reduced pain in most of the people who took it. No noticeable side effects were observed. So palmitoylethanolamide does not cause drowsiness or headache.

The Dutch researchers summarised the positive aspects of palmitoylethanolamide once again at the end of their review.

"Palmitoylethanolamide acts as a safe analgesic compound in nerve compression", they wrote. "Its safety and efficacy profile supports the clinical use of palmitoylethanolamide in compression syndromes such as sciatic pain and carpal tunnel syndrome."

"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 a stand-alone analgesic as well as part of a multimodal therapy regime."

J Pain Res. 2015 Oct 23;8:729-34.

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