Palmitoylethanolamide (PEA) is an evidence-based analgesic and anti-inflammatory nutraceutical that may be taken for a considerable array of chronic and acute pain conditions commonly encountered in clinical practice.

Based on research findings, practitioners may consider the following dosing recommendations as outlined below:

• Clinically effective dose: Clinical trials demonstrate that doses of 300 – 600 mg/day are effective. Depending on the condition, a loading dose of 600-1200mg may be required, followed by a maintenance dose of 300-600mg/day,^1,2 divided into two to four doses of 150 mg throughout the day for the best clinical results.
• Duration: PEA has been used for 10-180 days.³ However, supplementation should be restricted to no more than 21 consecutive days.
• Form: Absorption of the form PEA as Levagen+ with LipiSperse® technology provides enhanced bioavailability when compared to standard PEA forms.
• Drug interactions: No drug interactions have been reported in the literature to date.¹ PEA has demonstrated good tolerability and safety when used on its own or in conjunction with standard pain medications. ^5,6
• Safe Dosing: PEA is safe in adults at a dose-range of up to 50-100 mg/kg bodyweight, with no clinically relevant or dose limiting side effects.⁷
• Consider use in combination with anti-inflammatory nutrients such as Curcumin, EFAs, Ginger and Bromelains to create synergistic actions when pain is a symptom.

Clinical Research Update on PEA and Pain

In 2019, a qualitative systematic review of 47 clinical studies was published in order to support the pain-relieving effects of PEA across a broad range of conditions. It complements a smaller meta-analysis from 2017 which involved 10 studies on the use of PEA for the treatment of acute or chronic pain,⁸ and adds further compelling evidence for its efficacy across a broad range of conditions.⁴

Adding to this growing body of evidence is an Australian comparative, double-blind, randomized placebo controlled clinical trial in 111 adults aged 38-76 years with mild to moderate knee osteoarthritis. Published in 2019, the study assessed the efficacy of PEA at two different daily doses over an eight-week period. Participants received either 300 mg/day (A300) of PEA, or 600 mg/day (A600), or placebo. Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), while secondary outcomes included the Numerical Rating Scales (NRS) for pain, the Depression Anxiety Stress Scale (DASS), the Perceived Stress

Scale (PSS), the Pittsburg Sleep Quality Index (PSQI), the Short Form Health Survey (SF-36), the use of rescue pain medication and a clinical safety assessment. Compared to placebo, a significant reduction was observed in total WOMAC scores in the A300 (p=0.0372) and A600 group (p=0.0012) groups, the WOMAC pain score (A300, p=0.0074; A600, p≤0.001), the WOMAC stiffness score (A300, p<0.0490; A600, p=0.001) and in the WOMAC function score in the A600 group (p=0.033). Significant reductions also occurred in the NRS pain evaluations for “worst pain” and “least pain” in the A300 group (p<0.001, p=0.005) and the A600 group (p<0.001, p<0.001); as well as in anxiety (DASS) in both active treatment groups (A300, p=0.042; A600, p=0.043). Clinical markers remained unchanged and no serious adverse effects were reported.⁹

Background information on PEA

PEA is an endogenously produced cannabimimetic saturated fatty acid⁴ that was first identified in egg yolk, soybean and peanut oil in 1957. It has anti-inflammatory and analgesic properties^3,6 and is well-supported in the scientific literature, which supports its efficacy for a diverse range of conditions associated with pain and non-pain symptoms (see Table 1 below).^3,4

PEA is produced by the body in response to stress, inflammation, injury and pain. It was first thought to reduce the degranulation of mast cells, however, PEA has been shown to produce a variety of actions in the body. Most of its biological effects are thought to occur secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α).^5,6

PPARs are also found on both dorsal root ganglion sensory neurons and glial cells. As such, PEA may activate these receptors and modulate both the perception and transmission of peripheral pain signalling and spinal amplificatory pain mechanisms, thus exerting its activity in different types and phases of pain.¹

Despite sharing the same biosynthetic pathways as the endocannabinoid anandamide (AEA), PEA does not bind to classical cannabinoid receptors (CB1, CB2) to a significant degree. PEA’s pharmacological actions have been explained via an ‘entourage effect’, whereby “PEA enhances the anti-inflammatory and anti-nociceptive activity of other endogenous compounds by potentiating their affinity for a receptor, or by inhibiting their metabolic degradation”.¹⁰

Table 1 | Conditions for which human evidence supports the clinical use of PEA at specific dosages

References

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