It is quite wel known that palmitoylethanolamide (PEA) can be used together with other painkillers to enhance the efficacy, and create a better painkilling effect. Doctors from the university of Mexico could prove that PEA increases the painkilling effects of tramadol, a well known opiate, in a special model for pain treatment.

PEA and tramadol, given together leads to a so called synergistic interaction: 1 + 1 = 3. Together the compounds create more painkilling that separately.

The scientists further discovered that the painkilling effects of the combination between PEA and tramadol had positive effects on a number of receptors in our nerve system: the opioid receptor, the so called TRPV1 receptor, and the nuclear receptor known as the PPAR-α receptor.

Also quite important was the finding that the sedative effect of PEA together with tramadol was clearly less than that of tramadol alone!

The scientists concluded that their findings implied that PEA administered together with tramadol resulted in a stronger painkilling effect and at concentrations with very low side effects.

PEA natural painkiller

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Palmitoylethanolamide: useful to boost painkilling effects of tramadol

Palmitoylethanolamide may therefore be useful in the treatment of chronic severe pain, when doctors start prescribing opioids. We prefer to boost the painkilling effects of opioids either Italian PEA tablets, based on PEA-um or PEA-m, or Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain pharmaceutical fillers and are 100% pure.

“Only for these two formulations long term safety and efficacy data are available. And only for these formulations there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for me-too PEA formulations.”


Déciga-Campos M, Ramírez-Marín PM, López-Muñoz FJ.
Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test.
Eur J Pharmacol. 2015 Oct 15;765:68-74. doi: 10.1016/j.ejphar.2015.08.025. Epub 2015 Aug 19.