A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis
The aim of the study was to assess the safety, tolerability and efficacy of palmitoylethanolamide (PEA) when dosed at 300 mg and 600 mg per day on symptoms of knee osteoarthritis.
This was a single site, comparative, double-blind placebo controlled study in adults with mild to moderate knee osteoarthritis with 111 participants randomized to receive 300 mg PEA, 600 mg PEA or placebo each day, in divided doses b.i.d, for 8 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The secondary outcomes were 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 clinical safety assessment.
There was a significant reduction in the total WOMAC score in the 300 mg PEA (p = 0.0372) and the 600 mg PEA (p = 0.0012) groups, the WOMAC pain score (300 mg PEA, p = 0.0074; 600 mg PEA, p = < 0.001), the WOMAC stiffness score (PEA 300 mg, p < 0.0490; 600 mg PEA, p = 0.001) and in the WOMAC function score in the 600 mg PEA group (p = 0.033) compared to placebo. The NRS pain evaluations for "worst pain" and "least pain" were significantly reduced in the 300 mg PEA group (p < 0.001, p = 0.005) and the 600 mg PEA group (p < 0.001, p < 0.001) compared to placebo. There was a significant reduction in anxiety (DASS) in both active treatment groups (300 mg PEA, p = 0.042; 600 mg PEA group (p = 0.043) compared to placebo. There were no changes in the clinical markers and the product was well tolerated.
The study demonstrated that palmitoylethanolamide may be a novel treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis. Further studies on the pharmacological basis of this anti-inflammatory effect are now required.
KeywordsInflammation Osteoarthritis Pain Palmitoylethanolamide N-acylethanolamines
Compliance with ethical standards
Conflict of interest
Luis Vitetta has received National Institute of Complementary Medicine and National Health and Medical Research Council of Australia competitive funding and Industry support for research into nutraceuticals and herbal medicines. This research project was industry funded. None of the authors have a commercial interest in the investigative product. None of the authors have declared any conflict of interest.
- Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M et al (2010) P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide. Eur J Neurol. 17(S3):295Google Scholar
- Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 15:1833–1840Google Scholar
- Canteri L, Petrosino S, Guida G (2010) Reduction in consumption of anti-inflammatory and analgesic medication in the treatment of chronic neuropathic pain in patients affected by compression lumbosciatic pain, due to treatment with Normast 300 mg. Dolor 25:227–234Google Scholar
- Cobellis L, Castaldi MA, Giordano V, Trabucco E, De Franciscis P, Torella M et al (2011) Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study. Eur J Obstet Gynecol Reprod Biol. 158:82–86CrossRefGoogle Scholar
- Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V (2011) Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med. 102:141–147Google Scholar
- Costa B, Comelli F, Bettoni I, Colleoni M,Giagnoni G (2008) The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors. Pain. 139 541–550.CrossRefGoogle Scholar
- Desio P (2011) Combination of oxycodone and palmitoylethanolamide for low back pain treatment. AMC. 1:62–71Google Scholar
- Esposito E, Cuzzocrea S (2013) Palmitoylethanolamide is a new possible pharmacological treatment for the inflammation associated with trauma. Mini Rev Med Chem. 13:237–255Google Scholar
- Evangelista M, Cilli V, De Vitis RE, Militerno A, Fanfani F (2018) Ultramicronized palmitoylethanolamide effects on sleep-wake rhythm and neuropathic pain phenotypes in patients with carpal tunnel syndrome: an open-label, randomized controlled study. CNS Neurol DIsord Drug Targets. 17:291–298CrossRefGoogle Scholar
- Hawker GA, Mian S, Kendzerska T, Fench M (2011) Measures of adult pain: visual analog scale for pain (VAS Pain), numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), short-form McGill pain questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res. 63:S240–S252 (UP1 11).CrossRefGoogle Scholar
- Man GS, Mologhianu G (2014) Osteoarthritis pathogenesis - a complex process that involves the entire joint. J Med Life. 7:37–41Google Scholar
- Marini I, Bartolucci ML, Bortolotti F, Gatto MR, Bonetti GA (2012) Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. J Orofac Pain. 26:99–104Google Scholar
- Paladini A, Fusco M, Cenacchi T, Schlevano C, Piroll A, Varrassi G (2016) Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician. 19:11–24Google Scholar
- Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G (2016) Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician. 19:11–24Google Scholar
- Schifilliti C, Cucinotta L, Fedele V, Ingegnosi C, Luca S, Leotta C (2014) Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients. Pain Res Treat. 2014:849623Google Scholar
- Stensson N, Ghafouri N, Emberg M, Mannerkorpi K, Kosek E, Gerdie B et al (2018) The relationship of endocannabinoidome lipid mediators with pain and psychological stress in women with fibromyalgia: a case-control study. J. Pain. S1526–5900(18):30197–30204Google Scholar