Exercise, endocannabinoids and natural highs

The benefits of exercise on the mind and the body are widely pronounced, with even moderate amounts decreasing the risk for heart disease, stroke, diabetes, dementia, depression, aggression and Alzheimer's, to name a few. Those of us who exercise regularly may also know first hand of the almost immediate mood enhancing benefits of exercise, often touted as "runner's high". However, the exact mechanisms for this emotional boost are still unknown. Once believed to be the result of endorphins, natural opioid peptides released in the body that resemble synthetic opiates, working as analgesics and creating feelings of euphoria, this idea has recently come under scrutiny. The molecules creating these opioid peptides are too large to pass through the blood-brain barrier, meaning that endorphins released in the blood stream during exercise would be unable to make their way into the brain. However, a different endogenous drug system has begun to garner attention, and some researchers are instead now focusing on endocannabinoids, the organic derivative of cannabis, or marijuana, found in the body. Endocannabinoids are made up of lipids, which are small enough to pass through the blood-brain barrier when released in the blood stream, and have similar effects of reducing pain and anxiety and fostering feelings of well-being. A number of studies published in recent years (and succinctly summarized here by the New York Times), have looked at the endocannabinoid system and exercise in mice and have found strong links between the two. Neuroscientists in Rome using single cell recordings in the striatum (the region touted as the pleasure center of the brain) discovered that both running and sucrose consumption increased the sensitivity of cannabinoid receptors in the striatum, indicating a greater activation of the pleasure system. This upregulation in cannabinoid transmission also helped to serve as a protective factor for the mice when stressors were introduced into the environment, providing neurological support for the claims that exercise can have strong emotional benefits, preventing stress, anxiety and depression.

Another study investigating the pleasurable effects of running researched mice specifically bred without cannabinoid receptors in the brain. Researchers in France discovered that mice deficient in cannabinoid receptors ran 30-40% less over the course of a week than normal mice. Taken with the other mood-enhancing benefits of running, this further suggests that endocannabinoids are involved in the pleasure derived from exercise.

A seemingly paradoxical alternative effect of endocannabinoids is their role in eating as well as exercise. Endocannabinoids are responsible for some of the pleasure derived from food, and in addition to the analgesic and anxiolytic effects, medicinal marijuana is also used to stimulate patients’ appetite, which can be affected by terminal illnesses or treatment. Recently, a team of scientists at the University of California, Irvine discovered that endocannabinoids not only provoke hunger and provide pleasure when we eat, but also increase desire and urges for fatty foods in particular. In a study published this month in PNAS, researchers fed rats a sham liquid diet high in fat content (sham diets work by draining the contents of the stomach before the meal is digested, meaning that only the taste and act of consumption are registered, not the actual nutritional value or satiety signals). The diet high in fat, but not ones of primarily sugar or protein, selectively increased levels of endocannabinoids in the intestines. However, when the vagus nerve (responsible for taste) was cut, this increase of endocannabinoids in the stomach did not occur. This suggests that it is the taste sensation of the fat and communication from the brain to the GI tract that elicits this release. This elevation of endocannabinoids also affected metabolic processes in the stomach, creating a feedback loop where signals were sent back to the brain creating a greater demand for more high fat foods. Conversely, when endocannabinoid antagonists (drugs that decrease the amount of endocannabinoids in the body) were given to the rats, they selectively consumed less high fat solution, but did not alter intake of their normal food chow. This study provides strong evidence for the fat-specific effect endocannabinoids have on appetite and craving, potentially creating a perpetuating cycle of demand and consumption of high fat foods.

The paradoxical effects of endocannabinoids on the brain suggest that they have much to do with pleasure, and while they may encourage a binge on potato chips, at least they will also help you enjoy burning them off afterwards.