Exercise, The Miracle Drug


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By E. Dylan Mayer

Levels of anxiety, stress and depression are at all-time highs during the COVID-19 pandemic, and there is little doubt that this compromised state of our mental wellness will continue into the next year. Many of us are in lockdowns, unable to gather with family & friends during the holidays and feeling claustrophobic from doing everything at home. While these negative emotional feelings are to be expected during a situation as unique as this one, my experience both as a neuroscience major and fitness enthusiast have taught me something about exercise and brain chemistry: physical exercise is not only good for your body, but it also has profound effects on your brain.

The Centers for Disease Control and Prevention recommend that adults get at least 150 minutes of moderate-intensity aerobic activity per week.1 Even though we have always known that regular exercise is good for your metabolic and cardiovascular health, a large body of scientific evidence demonstrates that it is equally important for our brain, mental health and overall well-being. While it is known that physically active people have lower rates of anxiety and depression than sedentary people,2 do we know how regular running or walking or working out in the gym can affect the brain? There are at least 4 major mechanisms which have been implicated.

Exercise helps stimulate parts of your brain that aren’t as responsive when you’re feeling depressed. More so, exercise promotes the release of endorphins – the “feel-good” neurotransmitter3 – which has a similar structure and acts on similar receptors as morphine does. Exercise-induced endorphin release is thought to be one of the mechanisms behind “runner’s high”, but unlike morphine, endorphin receptor activation does not lead to addiction or dependence.4

Exercise not only affects endorphin levels in the brain, but it also affects the release of other neurotransmitters such as dopamine, norepinephrine and serotonin, all of which are important chemicals involved in mood regulation.5 Similar to the effect of a certain class of antidepressants, like Prozac, exercise induced increases in brain levels of serotonin boosts your mood6 and overall sense of well-being. It can also help improve your appetite and sleep cycles, which are often negatively affected by depression.7

Several laboratory studies have demonstrated a beneficial effect of regular exercise on important brain chemicals. Researchers found that mice with free access to a running wheel versus those which did not, had significantly higher levels of brain-derived neurotrophic factor (BDNF) production.8 Not only does BDNF promote regional brain growth, it is also associated with cognitive improvement and the alleviation of depression and anxiety.9 The main target of BDNF is in the hippocampus which exerts an inhibitory influence on stress and emotion regulation systems – the limbic system – in the brain. The limbic system is made up of numerous structures including the amygdala, thalamus, hypothalamus, hippocampus, corpus callosum, as well as several other brain structures, and is responsible for managing psychological responses to emotional stimuli.

Another well know effect of regular aerobic exercise is on vagal tone. People with anxiety, depression and chronic stress all show a reduction in cardiovagal tone and a lower heart rate variability. Some studies have shown that reduced vagal tone is a risk factor for heart disease. Vagal tone is regulated by brain regions involved in emotion regulation and central autonomic control, and the effect of regular exercise on the responsiveness of these regions is reflected in an increase in vagal tone. Regular exercise, like abdominal breathing (addressed in Suzanne Smith, NP article) are simple ways to increase your vagal tone and influence emotion regulating brain networks.

Regular exercise also has a beneficial effect on the gut microbiome and on gut microbiome brain interactions. Scientists found that exercise training alters the composition and functional capacity of the gut microbiota, independent of diet. While extreme forms of exercise, such as ultramarathons and triathlons can have a negative effect on gut health and systemic immune activation, ultimately affecting the brain, regular moderate exercise may reduce neuroinflammation in the brain and associated symptoms of fatigue and negative mood.10

In summary, regular aerobic exercise has been shown to positively affect the brain, mood states and stress responsiveness. Over hundreds of thousands of years of evolution, humans have been optimized to run, and are rewarded for this physical activity by not only feeling good, but by receiving many unexpected benefits as well.


  1. www.cdc.gov/physicalactivity/basics/adults/
  2. www.ncbi.nlm.nih.gov/pmc/articles/PMC474733/
  3. www.healthline.com/health/depression/exercise#Developing-an-exercise-routine
  4. www.webmd.com/depression/guide/exercise-depression#1
  5. www.healthline.com/health/depression/exercise#Developing-an-exercise-routine
  6. www.apa.org/topics/exercise-stress
  7. www.healthline.com/health/depression/exercise#Developing-an-exercise-routine
  8. www.sciencedaily.com/releases/2016/06/160602083254
  9. elifesciences.org/articles/15092
  10. journals.lww.com/acsm-essr/Fulltext/2019/04000/Exercise_and_the_Gut_Microbiome__A_Review_of_the.4.aspx

E. Dylan Mayer is a graduate from the University of Colorado at Boulder, with a major in Neuroscience and minor in Business. He is currently completing his master’s degree in Human Nutrition from Columbia University. Dylan is fascinated by the close interactions between nutrition, exercise and human health, especially with regard to the brain-gut-microbiome system – and regularly posts his content on his Instagram (@mayerwellness).