Every so often a new potential drug or supplement treatment bobs up in the literature and is worth looking into. The latest one to pique my interest is palmitoylethanolamide (PEA to its friends).

The article I saw was this one in my monthly edition of the Faculty of Pain Medicine’s professional journal. Here is a link to a full-text, free article which summarizes the state of play with PEA.

I thought it might be fun to go through with the help of my dedicated, thoughtful, intelligent and engaged readership a process of deciding whether I should start recommending it to my patients. For starters I’ll set out my thoughts which can then be critiqued and added to in the comments. Further evidence can be sought and discussed. We can also have a discussion about the threshold for deciding when to drop the objections and start using it in practice.

Are you along for the ride?

So here’s what I’ve done so far.

The above full-text article seems to me to do a fairly good job of setting out the rationale for thinking that PEA could be helpful for neuropathic pain. The first step I use in assessing a potential treatment that I haven’t heard about before is to check out the claimed mechanism of action to see if it’s plausible. So I go to PubMed and chuck in a fairly general search item, which returns a page like this. Scrolling down the linked articles, I am able to access several which give an account of the proposed mechanism by which PEA might have analgesic effects. The findings about PEA and its role in regulating proteins involved in signalling pathways of both pain and inflammation are part of wider research within a fairly mature field of inquiry. So the first step is achieved. Accepting that PEA might work as an analgesic compound does not seem to require any new science, and is completely compatible with what is already known about endogenous lipids. In fact, given its structural similarity to anandamide, which is one of the main endocannabinoid system regulators, it not only seems plausible but no surprise that it might be useful. Knowing how it is proposed to work can also enable us to make predictions about the sorts of pain that it might treat.

Having decided that it is indeed worth looking more closely, the next step is to look at the reported observations that form the basis of the deduction that PEA may be an analgesic. The initial study that prompted my interest was an observational case series involving several different types of neuropathic pain. I also can find case series with objective outcome data (not just patient self-reported outcomes) in Carpal Tunnel Syndrome, and chemotherapy-induced neuropathy,. Importantly, there is not just a single researcher’s name which keeps cropping up in all these papers. They are mostly from Italy, but there are some papers from other parts of Europe and the US as well. The presence of multiple sites of reporting helps to defuse the suspicion that this novel treatment is just a crank idea pushed by a couple of individuals with monomania.

What about randomized controlled trials of PEA? We have the supportive basic science and observational studies. The next step is high-quality RCTs to confirm efficacy versus placebo, and also head-to-head trials against other accepted analgesics.

Here we begin to stumble.

While the case reports and observational studies look good, there still remains a paucity of RCT data. Not surprising given that the ink is barely dry on most of the basic science and observational studies. I can find a small RCT of PEA vs ibuprofen for temperomandibular pain which has good methodology but a very small sample size (24 patients) which favours PEA. Another Italian pilot study used it for postoperative pelvic pain with some benefit. In this study PEA though better than placebo was not superior to celecoxib, which is the standard anti-inflammatory of choice for postoperative pain.

Does anyone think it’s time to head out and buy shares in PEA farms yet? Let’s discuss it!