Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy

Abstract

Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta‐analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49 days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60 days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head‐to‐head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head‐to‐head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.

Short-term efficacy of a fixed association of Palmitoylethanolamide and other phytochemicals as add-on therapy in the management of chronic pain in elderly patients: a real-world retrospective study

“…PEA (N-2-hydroxyethyl) hexadecamide, palmidrol belongs to the family of N-acylethanolamines and is an active anti-inflammatory agent. 15 There is evidence that PEA has analgesic proprieties without side effects in humans. 15 In an animal study, PEA was administered in combination with tramadol showing its enhanced analgesic efficacy also at lowdoses.…”

“…15 There is evidence that PEA has analgesic proprieties without side effects in humans. 15 In an animal study, PEA was administered in combination with tramadol showing its enhanced analgesic efficacy also at lowdoses. 16 Rosemary, Rosmarinus (R.) officinalis L. has analgesic, anti-inflammatory and anti-neurodegenerative properties.…”

“…14 In particular, four phytochemicals have received growing attention as adjuvant agents for the treatment of pain: Palmitoylethanolamide (PEA), Rosemary, Commiphora molmol (myrrh), β-Caryophyllene. [15][16][17][18] In particular, the role of PEA on endocannabinoid system activation and its anti-inflammatory properties are well known. 19,20 These agents are currently marketed in EU as nutraceuticals in humans.…”

N‐Palmitoyl Ethanol Amide Pharmacological Treatment in Patients With Nonsurgical Lumbar Radiculopathy

“…PEA is a member of the fatty‐acid ethanolamide family described in 1957, which is synthetized from the common phospholipid precursor of anandamide (endocannabinoid acting on CB 2 receptors) and therefore is thought to potentiate the action of endocannabinoids to reduce pain and inflammation . Its evaluation in the treatment of neuropathic pain had already begun in 1975, and preclinical studies point out how PEA can be effective in several models of pain including sciatic nerve ligature of neuropathic pain, although it has no action in acute thermal pain . PEA does not display a unique biochemical mechanism, and many biological targets are able to evocate its pharmacological response .…”

Endocannabinoids and Related Lipids in Chronic Pain: Analytical and Clinical Aspects

“…In addition to drugs interacting with the EC system, PEA has been widely investigated as an additive during various chronic pain conditions such as FM. Currently, PEA is marketed as a nutraceutical (Normast™, Pelvilen™, and PeaPure™ ) in some European countries (e.g., Italy and Spain) and is used as a food supplement in other countries (e.g., Netherlands) [143]. A meta-analysis of twelve studies showed that PEA elicits a progressive reduction of pain intensity significantly higher than controls and the PEA effects were independent of patient age or gender and not related to the type of chronic pain [144].…”