PEA delayes opiate tolerance: a special characteristic of a natural painkiller

Many patients suffering from chronic pain states are prescribed opioids. It is well known that once started on opioids some patients need step by step more and more.Therefore the new findings that PEA can spare opioids is of great use. It was already a known fact for some patients en pain physicians that if one prescribes opioids together with PEA, doses of opioids can remain low and the painkilling effect of the combination is impressive.One needs more and more due to a phenomena called ‘tolerance to the antinociceptive effect.’ Antinociceptive effect stands for painkilling effect.

The biological mechanisms behind morphine tolerance are not yet fully understood.Most probably the activation of non-neuronal cells in the brain and the release by these cells of proinflammatory molecules might explain the problem.

The scientists daily administered PEA to morphine treated rats and found that PEA could significantly inhibit the development of tolerance. More important PEA could increase the the number of days of morphine’s painkilling effect, compared to a controle group.

PEA also could prevent the increase in pro inflammatory cells triggered by the opiate in the central nervous system and decreased the pro inflammatory molecule release from the glia cells.

The authors concluded:

PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid based therapies is suggested.

Use of PEA together with opiates

We prefer treatment with a special PEA formulation, containing micro-PEA, as those treatments are most probably the best. MicroPEA can be found either in the Italian PEA tablets, based on PEA-um or PEA-m, or by administrating the Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain any chemical excipients and are 100% pure in vegetarian capsules.

Only for these the Dutch and the Italian formulations long term safety and efficacy data gathered under the supervision of MDs are available. And only for these formulations (containing microPEA) there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for cheap me-too PEA formulations.


Di Cesare Mannelli L, Corti F, Micheli L, Zanardelli M, Ghelardini C. Delay of morphine tolerance by palmitoylethanolamide. Biomed Res Int. 2015;2015:894732. doi: 10.1155/2015/894732. Epub 2015 Mar 22.1.