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