Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study

Overview

Journal Front Neurol

Specialty Neurology

Date 2018 Sep 5

PMID 30177906

Citations 15

Authors

Domenico Chirchiglia

Erika Cione

Maria C Caroleo

Minyan Wang

Giulio Di Mizio

Noemi Faedda

Teodosio Giacolini

Serena Siviglia

Vincenzo Guidetti

Luca Gallelli

Affiliations

Soon will be listed here.

Abstract

Palmitoyl ethanol amide (PEA) is an endogenously produced substance showing anti-nociceptive effect through both receptor and non-receptor mediated effects at the level of different cellular and tissue sites. This study showed the results of a single blind study that was conducted to evaluate both the safety and the efficacy of ultramicronized PEA (umPEA; 1,200 mg/day) for up 90 days in patients suffering of Migraine with Aura (MA) treated with NSAIDs. A total of 20 patients, 8 male (33-56-years, average 41.4 ± 7.8) and 12 female (19-61-years, average 38.5 ± 11.9) with MA were admitted to our observation and diagnosed according to ICHD-3 criteria, they received umPEA (1,200 mg/day) in combination with NSAIDs for up to 90 days. They were revaluated at 30, 60, and 90 days after treatment. umPEA administration induced a statistically significant and time dependent pain relief. In particular, these effects were evident at 60 days (male = 0.01189; female = <0.01) and they lasted until the end of the study (male = 0.0066; female = 0.01473). Although further studies are needed, our findings indicate that in patients suffering of MA treatment with umPEA had good efficacy and safety which candidate this compound as a therapeutic tool in pain migraine management.

Citing Articles

The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized-Palmitoylethanolamide Oral Supplementation in Clinical High-Risk State for Psychosis.

Bortoletto R, Garzitto M, Piscitelli F, Fornasaro S, Scipioni C, Sepulcri O Brain Sci. 2025; 14(12.

PMID: 39766429 PMC: 11727594. DOI: 10.3390/brainsci14121230.

Hallmarks of primary headache: part 1 - migraine.

Raggi A, Leonardi M, Arruda M, Caponnetto V, Castaldo M, Coppola G J Headache Pain. 2024; 25(1):189.

PMID: 39482575 PMC: 11529271. DOI: 10.1186/s10194-024-01889-x.

Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis.

Schweiger V, Schievano C, Martini A, Polati L, Del Balzo G, Simari S Nutrients. 2024; 16(11).

PMID: 38892586 PMC: 11174044. DOI: 10.3390/nu16111653.

Non-Pharmacological Treatments in Paediatric Migraine.

Baglioni V, Bozza F, Beatrice A, Cameli N, Cinnante E, Lentini G J Clin Med. 2024; 13(5).

PMID: 38592096 PMC: 10932388. DOI: 10.3390/jcm13051278.

Effectiveness of Palmitoylethanolamide (Levagen+) Compared to a Placebo for Reducing Pain, Duration, and Medication Use during Migraines in Otherwise Healthy Participants-A Double-Blind Randomised Controlled Study.

Briskey D, Skinner R, Smith C, Rao A Pharmaceuticals (Basel). 2024; 17(2).

PMID: 38399360 PMC: 10892859. DOI: 10.3390/ph17020145.

References

Gallelli L, Iannacchero R, De Caro E, Peltrone F, Colosimo M, De Sarro G . A questionnaire-based study on prevalence and treatment of headache in young children. J Headache Pain. 2005; 6(4):277-80. PMC: 3452000. DOI: 10.1007/s10194-005-0206-x. View

Mayans L, Walling A . Acute Migraine Headache: Treatment Strategies. Am Fam Physician. 2018; 97(4):243-251. View

Varrassi G, Fusco M, Coaccioli S, Paladini A . Chronic pain and neurodegenerative processes in elderly people. Pain Pract. 2014; 15(1):1-3. DOI: 10.1111/papr.12254. View

Cerrato S, Brazis P, Della Valle M, Miolo A, Puigdemont A . Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Vet Immunol Immunopathol. 2009; 133(1):9-15. DOI: 10.1016/j.vetimm.2009.06.011. View

Steiner T, Stovner L, Vos T . GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain. 2016; 17(1):104. PMC: 5108738. DOI: 10.1186/s10194-016-0699-5. View

Chirchiglia D, Della Torre A, Signorelli F, Volpentesta G, Guzzi G, Stroscio C . Administration of palmitoylethanolamide in combination with topiramate in the preventive treatment of nummular headache. Int Med Case Rep J. 2016; 9:193-5. PMC: 4957685. DOI: 10.2147/IMCRJ.S106323. View

Palleria C, Di Paolo A, Giofre C, Caglioti C, Leuzzi G, Siniscalchi A . Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci. 2014; 18(7):601-10. PMC: 3897029. View

Gallelli L, Staltari O, Palleria C, De Sarro G, Ferraro M . Hepatotoxicity induced by methimazole in a previously healthy patient. Curr Drug Saf. 2009; 4(3):204-6. DOI: 10.2174/157488609789006912. View

Keppel Hesselink J . Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. Int Med Case Rep J. 2013; 6:49-53. PMC: 3775671. DOI: 10.2147/IMCRJ.S51572. View

10.

Raggi A, Schiavolin S, Leonardi M, Giovannetti A, Bussone G, Curone M . Chronic migraine with medication overuse: association between disability and quality of life measures, and impact of disease on patients' lives. J Neurol Sci. 2014; 348(1-2):60-6. DOI: 10.1016/j.jns.2014.11.004. View

11.

Loria F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangomez M . Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci. 2008; 28(4):633-41. DOI: 10.1111/j.1460-9568.2008.06377.x. View

12.

. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053):1545-1602. PMC: 5055577. DOI: 10.1016/S0140-6736(16)31678-6. View

13.

Rice A, Farquhar-Smith W, Nagy I . Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostaglandins Leukot Essent Fatty Acids. 2002; 66(2-3):243-56. DOI: 10.1054/plef.2001.0362. View

14.

Luongo L, Guida F, Boccella S, Bellini G, Gatta L, Rossi F . Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targets. 2013; 12(1):45-54. DOI: 10.2174/1871527311312010009. View

15.

Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G . The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain. 2008; 139(3):541-550. DOI: 10.1016/j.pain.2008.06.003. View

16.

Chirchiglia D, Paventi S, Seminara P, Cione E, Gallelli L . N-Palmitoyl Ethanol Amide Pharmacological Treatment in Patients With Nonsurgical Lumbar Radiculopathy. J Clin Pharmacol. 2018; 58(6):733-739. DOI: 10.1002/jcph.1070. View

17.

Gabrielsson L, Mattsson S, Fowler C . Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016; 82(4):932-42. PMC: 5094513. DOI: 10.1111/bcp.13020. View

18.

Gallelli L, Gallelli G, Codamo G, Argentieri A, Michniewicz A, Siniscalchi A . Recognizing Severe Adverse Drug Reactions: Two Case Reports After Switching Therapies to the Same Generic Company. Curr Drug Saf. 2015; 11(1):104-8. DOI: 10.2174/1574886311207040309. View

19.

Skaper S, Facci L, Fusco M, Della Valle M, Zusso M, Costa B . Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology. 2013; 22(2):79-94. DOI: 10.1007/s10787-013-0191-7. View

20.

Gallelli L, Avenoso T, Falcone D, Palleria C, Peltrone F, Esposito M . Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium. Headache. 2013; 54(2):313-24. DOI: 10.1111/head.12162. View