Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data

Abstract

Background: Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD. Objective: Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model. Methods: To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase. Results: Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats. Conclusion: Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.