Eid al-Fitr was recently celebrated on Friday, April 21st, where the Muslim community commemorated the end of the month-long dawn-to-sunset fasting of Ramadan. Fasting is when you do not eat or you consume limited amounts of food or drinks for a period of time. Typical periods of fasting last 12 hours a day to up to three weeks—however this does not mean an individual stopped eating altogether (that would be starvation) (Longo & Matson, 2014). While people undergo periods of fasting, such as for religious, spiritual, or medical reasons, changes occur to some of our body’s systems and natural molecules—one being the endocannabinoid system.

The endocannabinoid system (ECS) has a wide range of influence on many different neuronal and biological functions, with one being the eating system. Our ECS naturally produces cannabinoids—anandamide (AEA) and arachidonoyl glycerol (2-AG)—and contain CB1 and CB2 receptors where cannabinoids bind (Skaper & Di Marzo, 2012; Lu & Mackie, 2016). Endocannabinoids in the brain play a role in appetite, body weight, and food reward systems. In the hypothalamus, endocannabinoids regulate the levels of different chemicals that control feeding and body weight, such as melanocortin, a hormone that reduces feeding (Cristino and Di Marzo, 2015). Furthermore, endocannabinoid levels in the hypothalamus correlate inversely with leptin levels—a hormone that deals with regulating appetite, hunger, and metabolism (Kunos et al., 2001). However, what happens to the body’s natural endocannabinoid levels when someone is fasting?

In one study, Kirkham et al. (2002) explored feeding-related changes in the brain’s endocannabinoid levels, specifically focusing on AEA and 2-AG in the hypothalamus and limbic forebrain—brain areas related to feeding and food reward. Researchers measured AEA and 2-AG levels in rats after a 24-hr food deprivation period. Furthermore, they also examine the action on food intake when administering 2-AG directly into the rats nucleus accumbens (a part of the limbic forebrain) to identify its association with the reward value of food and stimulation of feeding. The study found a significant increase in AEA levels in the rats limbic forebrain following food deprivation, as well as increased 2-AG levels in both the limbic forebrain and hypothalamus (Kirkham et al., 2002). Additionally, the administration of 2-AG in the limbic forebrain caused a significant hyperphagic action in rats, meaning that the rats were excessively over-eating. These findings suggest that during a fasting period, our body’s endocannabinoids will increase, and this overactivation of the endocannabinoid system may play a role in enhancing our motivation to eat.

In addition to fasting over-activating the endocannabinoid system, it may also be involved in producing fasting-induced pain relieving effects. The endocannabinoid system also plays a role in pain modulation by suppressing pain signaling by acting on cannabinoid receptors (Guindon & Hohmann, 2009; Roques et al., 2012). In a study conducted by Lee et al. (2020), they found that mice undergoing a 24-hr fasting period were showcasing fewer behaviors associated with pain (i.e. foot-licking) when given an inflammatory-induced solution, and this fasting-induced analgesia was reversed when rats were injected with a CB1 receptor antagonist. These findings may suggest that food intake and pain are likely to interact with each other in the CB1 receptors, and undergoing a fasting period may produce pain-relieving effects on the body.

When going through a fasting period, your body’s endocannabinoid system will go through some change in order to compensate for the lack of food intake, which can then influence other systems in your body. During fasting and having a decreased amount of food consumption, such as doing Ramadan, your body will produce more endocannabinoids in your system, being AEA and 2-AG, which may play a role in one’s motivation to eat again. Furthermore, this overproduction of endocannabinoids may also influence one’s ability to go through fasting-induced analgesia, seen through the results of the previous study mentioned. Further research into how fasting impacts our motivation to eat again and its ability to create analgesic effects may be important to fully understanding how the endocannabinoid system works in eating and feeding behaviors. If you or someone you know experienced a time of fasting due to religious, medical, or any other circumstance, you now have some insight into how your body works during it, as well as to why it may be difficult to not eat something during your fast.

References: 

Cristino, L., and Di Marzo, V. 2015. Established and Emerging Concepts of Cannabinoid Action on Food Intake and their Potential Application to the Treatment of Anorexia and Cachexia. In Handbook of Cannabis, ed. R. G. Pertwee. Oxford University Press.

Guindon, J., & Hohmann, A. G. (2009). The endocannabinoid system and pain. CNS & Neurological Disorders Drug Targets, 8(6), 403-421. https://doi.org/10.2174/187152709789824660

Kirkham, T. C., Williams, C. M., Fezza, F., & Marzo, V. D. (2002). Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2‐arachidonoyl glycerol. British Journal of Pharmacology, 136(4), 550-557. https://doi.org/10.1038/sj.bjp.0704767

Kunos, G., Di Marzo, V., Goparaju, S. K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G. I., Palmiter, R. D., & Sugiura, T. (2001). Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature (London), 410(6830), 822-825. https://doi.org/10.1038/35071088

Lee, J., Lee, G. J., Nakamura, A., Lee, P. R., Kim, Y., Won, C. H., Furue, H., & Oh, S. B. (2020). Involvement of cannabinoid type 1 receptor in fasting-induced analgesia. Molecular Pain, 16, 174480692096947-1744806920969476. https://doi.org/10.1177/1744806920969476

Longo, V., & Mattson, M. (2014). Fasting: Molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181-192. https://doi.org/10.1016/j.cmet.2013.12.008

Lu, H., & Mackie, K. (2016). An introduction to the endogenous cannabinoid system. Biological Psychiatry (1969), 79(7), 516-525. https://doi.org/10.1016/j.biopsych.2015.07.028

Roques, B. P., Fournié-Zaluski, M., & Wurm, M. (2012). Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nature Reviews. Drug Discovery, 11(4), 292-310. https://doi.org/10.1038/nrd3673

Skaper, S. D., & Di Marzo, V. (2012). Endocannabinoids in nervous system health and disease: The big picture in a nutshell. Philosophical Transactions of the Royal Society B: Biological Sciences, 367(1607), 3193-3200. https://doi.org/10.1098/rstb.2012.0313