CSF levels of the endocannabinoid anandamide are reduced in patients with untreated narcolepsy type 1: A pilot study

A. Romigi, M. Bari, C. Liguori, F. Izzi, C. Rapino, M. Nuccetelli, N. Battista, S. Bernardini, D. Centonze, N.B. Mercuri, F. Placidi, M. Maccarrone

Research output: Contribution to journalArticlepeer-review


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.

Original languageUndefined/Unknown
Pages (from-to)142-147
Number of pages6
JournalCNS and Neurological Disorders - Drug Targets
Issue number2
Publication statusPublished - 2020

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