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

Background The endocannabinoid system (ECs) is involved in excitatory/inhibitory balance mechanisms within the CNS. Growing evidence shows that endocannabinois may influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology, thus indicating that endocannabinoids may play an intrinsic role modulating sleep and wake. Objective To measure endocannabinoids levels in the CSF of drug-naive narcoleptic patients to test whether ECs is dysregulated in narcolepsy type 1 (NT1) and type 2 (NT2). Methods We analyzed narcoleptic drug-naïve patients compared to a sample of healthy controls. Patients and controls underwent lumbar puncture for CSF endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), levels assessment. Laboratory assessment of cerebrospinal fluid levels of ECs (AEA, 2-AG), orexin was perfomed. 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, AEA CSF level was related to CSF orexin levels in all subjects. Conclusion We hypothesize that the endocannabinoid system is dysregulated in NT1.