Efficacy of Palmitoylethanolamide (Levagen+<sup>TM</sup>) Compared to Ibuprofen for Reducing Headache Pain Severity and Duration in Healthy Adults: A Double-Blind, Parallel, Randomized Clinical Trial

Abstract

Background: Palmitoylethanolamide (PEA) has shown promise as an analgesic for those with chronic pain pathologies. With recently increased bioavailability, PEA may also be a treatment for acute pain presentations such as tension-type headaches. Aim: To assess the efficacy of a bioavailable PEA formulation (Levagen+ TM ) for reducing the severity and duration of acute episodes of tension-type headaches when compared to a standard treatment, nonsteroidal anti-inflammatory drug (NSAID) (the comparator). Methods:The study was a double-blind, randomized, single site, comparator controlled clinical study, with the cohort consisting of otherwise healthy adults, aged between 18 and 71, who experienced regular tension-type headaches. 94 adults experiencing headaches were randomised to receive either PEA (n = 47) or Ibuprofen comparator (n = 47). Upon headache onset, participants consumed their allocated product, recorded pain levels using a visual analogue scale (VAS) and continued to log their pain scores at 30-minute intervals for up to 4-hours. Results: Eighty-six participants (44 active treatment and 42 comparator) recorded at least one headache with a total of 271 tension-type headaches recorded (120 active treatment and 151 comparator). Most headaches were reduced in both treatment arms by 2 hours and almost all by 4 hours; 90% in the PEA group, and 97% in comparator group, p > 0.5. For moderate at onset headaches, the comparator group had a greater percentage of pain-free

Can Chronic Pain be considered a Disease of Civilization?

“…I revert to the body's endogenous analgesic, PEA. With excellent safety data [88,89] and efficacy in numerous models of pain [43,[45][46][47][48][89][90][91], it has recently been found to reduce inflammatory markers and stress in athletes [50] and in Covid patients [92]. Non-addictive and free from withdrawal effects, it attenuates cocaine cravings in pre-clinical models [93] and is currently being trailed for opioid reduction in below knee fracture fixation [94].…”

The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial

“…Unlike OTC medications such as ibuprofen and acetaminophen which inhibit the COX pathway, PEA's pleiotropic effects are likely due to its ability to affect multiple pathways at different receptor sites e.g., proliferator-activated receptor alpha (PPARα) and G protein-coupled receptor 55 (GPR55) receptors and indirectly on cannabinoid receptor type 1 and 2 (CB 1 and CB 2 ); amongst others [21]. Multiple intervention studies have found that PEA doses of between 300 and 1200 mg are effective in the management of pain associated with osteoarthritis and similar dosing relieves headache pain to a similar degree as ibuprofen [22][23][24][25]. Additionally, PEA has shown to improve sleep quality and duration, which may be of benefit to athletes as sleep deprivation has shown to negatively impact skeletal muscle hypertrophy and strength performance [26][27][28][29].…”

Efficacy of Topical Palmitoylethanolamide (Levagen+) for the Management of Eczema Symptoms: A Double-Blind, Comparator-Controlled, Randomized Clinical Trial

“…PEA is often used to treat both acute and chronic disease stages and has been recognised for its ability to regulate numerous systems involved in inflammation, pruritus, and pain with no documented side effects [17,18]. In eczemalesioned skin, PEA is naturally recruited in high levels, and this is hypothesised to be a direct response to enable the down regulation of mast cell activity and function [19,20].…”