Palmitoylethanolamide-based nutraceutical Calmux® in preventive treatment of migraine

Clin Neurol Neurosurg. 2022 Jul:218:107282. doi: 10.1016/j.clineuro.2022.107282. Epub 2022 May 8.


Background: The aim of this study was to determine the efficacy and tolerability of treatment with a Palmitoylethanolamide (PEA)-based nutraceutical in patients with episodic migraine.

Methods: A pilot, prospective, open-label experimental study was designed in which patients with episodic migraine with and without aura seen in the general practice office of a tertiary centre during a period of 6 month were offered the possibility to participate. No control group was included. All included patients were treated with nutraceutical Calmux® taken every 12 h for 3 months. Monthly attack frequency, attack intensity, impact of migraine (HIT-6 and MIDAS scales) and quality of sleep at baseline and after 3 months of treatment were compared.

Results: Twenty-five patients (22 women and 3 men) were included, with a mean age of 36.3 ± 12 years. Headache days per month decreased from 10 ± 2.1 days to 6.6 ± 3.6 days (p < 0.00001). Days of analgesic use decreased from 9.2 ± 2.6 days to 4.1 ± 2.1 (p < 0.0001). None of the patients included suffered from adverse events attributable to treatment. Pain intensity showed a mean reduction of 3.1 points, from 8.1 at baseline to 5 at 3 months of treatment (p < 0.005).

Conclusions: PEA nutraceuticals could be useful in migraine prevention. Further studies are necessary, but we consider that PEA-based nutraceutical could be a new approach in the treatment of migraine patients.

Keywords: Migraine; PEA; Palmitoylethanolamide; Preventive treatment.

Publication types

  • Clinical Study

MeSH terms

  • Adult
  • Amides
  • Dietary Supplements
  • Double-Blind Method
  • Ethanolamines
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders* / drug therapy
  • Migraine Disorders* / prevention & control
  • Palmitic Acids
  • Pilot Projects
  • Prospective Studies
  • Treatment Outcome
  • Young Adult


  • Amides
  • Ethanolamines
  • Palmitic Acids
  • palmidrol