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Can cannabis help with eating disorders?

What causes the munchies?
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There has never been a time in human history with as much abundance as we have today. We can choose what foods we eat, when we eat, and how we eat. Even so, we humans also suffer from a variety of eating disorders that are both physiological and psychological. The growing list of disorders has, in turn, led to an increasing list of pharmaceutical solutions. Anecdotally, cannabis has been attributed to appetite-enhancing effects, or as the experts like to call it, "The Munchies." Thus the question presents itself: can we make use of this cliche for medical purposes? Can cannabis help with eating disorders?—The answer: Probably.

Appetite

Maintaining our body's energy balance is critical to our survival. It is a delicate dance involving many cell types that dictate the biochemical processes responsible for digestion and energy storage. To that end, our central nervous system (CNS) is in constant communication with our gastrointestinal tract to shape our food-seeking behavior. Depending on our current nutritional status, energy expenditure, and circadian rhythm (daily internal clock), our brain will tell us whether it is time to order that extra-large meat lover's pizza or not. Antagonistic pathways that either stimulate or suppress appetite maintain the balance. For example, the sensation of hunger is encouraged by releasing the hormone "ghrelin" via cells of the gastrointestinal tract (mainly the stomach). Circulating ghrelin levels promote the production of neuropeptides in the brain (NPY, AgRP) that act as appetite-stimulating, or "orexigenic" signals.

Conversely, fat cells (adipocytes) can release a hormone called "leptin." Leptin blocks the production of neuropeptides in the brain that create the sensation of hunger. Instead, it promotes the production of "proopiomelanocortin" (POMC), which is a precursor for a variety of molecules that are involved in the "an-orexigenic system" that decreases appetite and food intake. 

The body's endocannabinoid system (ECS) also regulates eating behavior on multiple levels throughout the body. From the brain (hypothalamus, hindbrain, limbic systemto the intestinal system and fat (adipose) tissue. The ECS interacts with several peptides directly involved in appetite regulation, such as leptin, ghrelin, and melanocortins mentioned above. Beyond the direct actions on appetite, indirect actions must also be considered; the endocannabinoid system is expressed ubiquitously throughout the body. For example, endocannabinoids slow the transit of food through the stomach and colon by modulating the muscle movement that pushes the food through the intestines (peristalsis and contractility). The ECS also affects the permeability of the gut barrier, interacts with the microbiota (symbiotic gut bacteria commonly referred to as “probiotic”), reduces nausea, and influences the perception of taste. 

Using cannabis to combat loss of appetite (Anorexia).

Loss of appetite and associated weight loss is a common and disruptive side effect of some medical conditions and treatments. The best way to combat anorexia is to treat the underlying condition,so, if you are suffering from anorexia in response to a gastrointestinal infection, then clearing the disease will also eliminate the loss of appetite. FDA-approved drugs exist that can provide short-term relief against anorexia. Gut mobility stimulators like "metoclopramide" or steroids like "prednisone" and "megestrol acetate." They are effective, but can have significant adverse side-effects after prolonged use, making them less attractive for chronic anorexia or weight loss. Cannabinoid-based treatment approaches are conceptually appealing, as the long-term adverse effects are more manageable. The most reliable clinical data that exists today on the subject of cannabis and appetite has been accrued from clinical trials on HIV+ patients who often suffer from anorexia and weight loss. HIV+ patients who smoke cannabis or consume synthetic THC like dronabinol have significantly higher caloric intake and weight gain. This is likely a combination of the direct appetite-stimulating effect of cannabinoids, the secondary benefits of alleviating chronic pain, and the associated psychological discomfort. 

Cancer-related or chemotherapy-induced loss of appetite is another promising target for cannabinoid therapy. Anorexia (loss of appetite) is common among cancer patients and can either be due to the location of the cancer itself, the psychological impact of chronic pain, chemotherapy-induced nausea, or even loss of taste and salivary gland function after radiation therapy of the head and neck. Up to 90% of patients with advanced cancer suffer from some degree of anorexia. Along with that, cancer patients often have an increased metabolism, complicating things even further. This increase is called "cachexia" and manifests as wasting skeletal muscle and adipose (fat) tissue. 

Unfortunately, the available clinical trial data on cancer related anorexia-cachexia is much less conclusive. While there has been some success with dronabinol, there is trial data where cannabinoids showed no significant advantage over the control placebo. There is a need for better designed, larger scale, clinical trials that determine dose/concentration/effect relationships with different sources of cannabinoids and modes of administration.  With increasingly widespread cannabis use among cancer patients, there is also a clear need to evaluate drug interactions with chemotherapy agents and the toxicity of the various cannabinoids and terpenes contained in the full cannabis plant. Lastly, elderly cancer patients might not tolerate the secondary adverse effects of prolonged cannabis use, such as dysphoria, anxiety, or cognitive dysfunction, especially those with cancer. 

In conclusion, does cannabis provide a meaningful approach to treat chronic loss of appetite? The answer is still "probably yes," but we simply need more scientific data to be certain, especially in the context of cancer-related chronic anorexia. The real question is, does it matter? Treating pain and nausea are far bigger motivators to self-medicate with cannabis. So, suppose you are a cancer or HIV patient with such severe loss of appetite that you are considering cannabis: in that case you are likely already consuming cannabis to combat the chronic pain and nausea you are experiencing.  For short-term mitigation of anorexia, existing FDA-approved appetite stimulating drugs provide a more robust, more controlled solution.

References

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