Inflammation is another key pathway connecting exercise to mental health. While chronic inflammation is known to play a causative role in depression, the transient inflammation induced by exercise has beneficial effects. Every exercise session triggers a "myokine pulse," releasing hundreds of muscle-derived signaling molecules—known as myokines—into circulation. One especially important myokine in this context is interleukin-6 (IL-6).
Acute increases in IL-6 following exercise initiate a robust anti-inflammatory response in the subsequent hours, lowering chronic inflammation with training and shifting baseline physiology toward conditions less detrimental to mood-regulating brain circuits. Additionally, IL-6 and other myokines actively promote microglia in the brain toward a restorative, anti-inflammatory state rather than the harmful pro-inflammatory phenotype often observed in depression. Reduced inflammation driven by IL-6 also positively impacts the kynurenine pathway by limiting the diversion of tryptophan away from serotonin production.
Lower levels of BDNF are frequently observed in depression, with depressed individuals often displaying BDNF concentrations 10–20% lower than healthy counterparts. Successful antidepressant treatment commonly normalizes BDNF levels, highlighting its central role in mood regulation through neuroplasticity. Disruptions in neural plasticity—often driven by stress and adverse environmental stimuli—contribute significantly to the onset and progression of depressive symptoms. By stimulating neuroplasticity, elevated BDNF can reverse or mitigate these detrimental changes. Notably, no intervention has proven more effective at increasing BDNF levels than strenuous aerobic exercise.
Finally, there are endocannabinoids and endorphins. Endocannabinoids are naturally produced compounds that bind to receptors throughout the brain and immune system—the same receptors activated by cannabinoids like THC and CBD. These molecules play a significant role in generating the euphoric sensations often felt during moderate- to vigorous-intensity aerobic exercise.
Additionally, exercise triggers the release of beta-endorphins, the body’s own opioids that help reduce pain and enhance mood, famously associated with the "runner's high." Together, the endocannabinoid and endorphin systems contribute significantly to the mood-boosting effects of exercise, although they likely play a more supportive role when it comes to reducing depressive symptoms—a distinction likely reserved for kynurenine, BDNF, and inflammatory signaling.
Final Thoughts
The mood-elevating effects of a hard workout are what initially drew me to exercise, and I still find that high-intensity exercise is one of the best ways to sharpen my thinking and raise my spirits for several hours. I like to think of it as my "brain pill."
Of course, simple mood elevation is not the same as resolving symptoms of clinically diagnosed depression or anxiety, but they do share similar pathways.
It's clear based on the evidence that exercise should become a standard treatment for depression and anxiety. However, it remains underused and undervalued. Hopefully that will change as medical professionals, therapists, and other mental health experts become increasingly aware of exercise's powerful effects on its own or when combined with other pharmacological or behavioral therapies.
The biggest question often on people's minds is: "Ok then, how much do I need to exercise?"
The answer to this question might be less than you think.
I am an advocate of moving as much (and as vigorously) as possible—at least 150 minutes and up to 300 minutes or more per week. But for depression, the benefits might start at an even lower dose. In fact, the authors of the study noted that "Despite the findings from this review favoring the use of exercise to reduce symptoms of depression and anxiety, only three studies met the WHO weekly physical activity guidelines (volume and intensity) for both aerobic and resistance exercise."
For people with depression—or even those just seeking mood elevation—movement is the best medicine.
Warm regards
— Rhonda and the FoundMyFitness team
