CSF Levels of the Endocannabinoid Anandamide are Reduced in Patients with Untreated Narcolepsy Type 1: A Pilot Study

CNS Neurol Disord Drug Targets. 2020;19(2):142-147. doi: 10.2174/1871527319666200309115602.


Background: Endocannabinoids (ECs) modulate both excitatory and inhibitory components in the CNS. There is a growing body of evidence that shows ECs influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology. Therefore, ECs may influence sleep and sleep-wake cycle.

Objective: To evaluate EC levels in the CSF of untreated narcoleptic patients to test whether ECs are dysregulated in Narcolepsy Type 1 (NT1) and Type 2 (NT2).

Methods: We compared CSF Anandamide (AEA), 2-Arachidonoylglycerol (2-AG) and orexin in narcoleptic drug-naïve patients and in a sample of healthy subjects.

Results: We compared NT1 (n=6), NT2 (n=6), and healthy controls (n=6). We found significantly reduced AEA levels in NT1 patients compared to both NT2 and controls. No differences were found between AEA levels in NT2 versus controls and between 2-AG levels in all groups, although a trend toward a decrease in NT1 was evident. Finally, the CSF AEA level was related to CSF orexin levels in all subjects.

Conclusion: We demonstrated that the EC system is dysregulated in NT1.

Keywords: 2-arachidonoylglycerol; Endocannabinoid; anandamide; cerebrospinal fluid; narcolepsy type 1; narcolepsy type 2..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arachidonic Acids / metabolism*
  • Case-Control Studies
  • Endocannabinoids / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Narcolepsy / metabolism*
  • Orexins / metabolism
  • Pilot Projects
  • Polyunsaturated Alkamides / metabolism*
  • Rome
  • Sleep / physiology
  • Young Adult


  • Arachidonic Acids
  • Endocannabinoids
  • Orexins
  • Polyunsaturated Alkamides
  • anandamide