Narcolepsy is a life-limiting disorder and new research points to the involvement of the endocannabinoid system.
Imagine not being able to control when or where you fell asleep. Seems implausible, right? Well, that’s a reality for those with narcolepsy. Fortunately, cannabis might be able to help.
We’ve all heard about the myriad potential health benefits of cannabis. From helping you sleep, to easing your pain, to reducing your anxiety, it seems like there is nothing that cannabis can’t do. Certainly, the anecdotal evidence is strong and verified research is quickly catching up.
However, thanks to prohibition, science has fallen short when it comes to understanding exactly how cannabis works and what it does. Up to this point it has been nearly impossible to provide the scientific evidence to back up these anecdotes.
But thanks to the recent groundswell of support for cannabis reform, cannabis is now medically legal in 33 states. One interesting revelation to come from recent research is that cannabis might play an important role in fighting narcolepsy, a disorder that can cause people to instantly fall asleep.
Sleep and the Endocannabinoid System
The endocannabinoid system is a cell signaling system that induces a range of bodily responses through the involvement of cannabinoids. Cannabis contains active cannabinoids, which interact and bind to cannabinoid receptors, such as the G-protein coupled receptors CB1 and CB2. Yet, these compounds also act on receptor pathways and other non-cannabinoid receptors.
What is Narcolepsy?
Narcolepsy is a nervous system disorder that causes:
- Excessive daytime fatigue
- Sleep paralysis
- Cataplexy
Narcolepsy patients can fall asleep suddenly and instantly right in front of you. Narcolepsy patients also lose muscle control during sleep attacks. This makes daily activities, like driving, potentially very dangerous.
Orexin has been shown to play an important role in narcolepsy. After all, this condition is “caused by a deficiency of orexin-producing neurons in the lateral hypothalamus.” Moreover, one study on dogs showed that disruption to the orexin receptor gene, HCRTR2, causes narcolepsy. Orexin is a neuropeptide that the brain synthesizes. It regulates sleep, arousal, and appetite.
Orexin and Cannabis: Possible Partners
Research suggests that there may be a strong connection between the orexin and endocannabinoid systems. Both cannabinoid and orexin receptors have been found in the same area of the brain and form heterodimers (a protein complex, such as a receptor) in these areas. Cannabinoid and orexin receptors also activate the same intracellular signaling pathways.
According to Biochemical Pharmacology, another factor that shows interactions between the orexin and endocannabinoid systems is that the “activation of orexin receptors induces the synthesis of the endocannabinoid 2-arachidonoyl glycerol suggesting that the endocannabinoid system participates in some physiological functions of orexins”.
Orexins and endocannabinoid systems have also been found to interact through signaling at both structural and functional levels. These receptors co-express in the same regions of the body.
A Possible Joint Response To Fight Narcolepsy
Much like orexin, research has shown that cannabinoids regulate and induce sleep. One study found that signaling in the endocannabinoid system resulted in the hyperpolarization of orexin neurons. This suggests that cannabinoids may interact with orexin neurons.
One theory for how the endocannabinoid and orexin systems could work together to stop narcolepsy involves dorsal raphe nucleus (DRN) serotonergic neurons. DRN serotonergic neurons affect sleep cycles. These fire at high rates when you’re awake, at a lesser rate when you’re in non-REM sleep, and don’t fire at all during REM sleep. It’s possible that narcolepsy occurs when these DRN serotonergic neurons over fire. This throws off sleep patterns and leads to the fragmented wakefulness of narcolepsy.
One rat model study showed that orexin stops the activation of DRN serotonergic neurons through retrograde endocannabinoid messengers. This could control the excessive activation of DRN serotonergic neurons that may lead to narcolepsy.
Other Combined Orexin-Cannabis Responses
The orexin and endocannabinoid systems induce results in a range of other bodily functions.
Both orexin and cannabinoids may play an important role in fighting painful gut disorders, such as irritable bowel disease. One study found that with the introduction of a CB1 or CB2 receptor blocker, orexin-induced antinociception in the colon was also blocked. Antinociception refers to the blocking of pain in sensory neurons, which would be incredibly helpful to those who suffer from painful IBD.
Orexin is also able to control appetite. Cannabinoid signaling may also play a role here as cannabinoid receptors appear in the area of the hypothalamus associating with feeding regulation. One study showed that neutralized cannabinoid receptors seem to decrease orexin activity levels. This led to a significant reduction in food intake of the animal subjects.
We don’t fully understand the interaction between orexin and cannabinoids, but these systems seem to have an important relationship. This link will hopefully lead to positive results for those suffering from chronic, debilitating conditions like narcolepsy and IBD.
