Depression is one of the most common mental health disorders worldwide—and one of the most debilitating.

While conventional treatments like medication and cognitive behavioral therapy (CBT) can be effective, a growing body of research shows that physical activity deserves a seat at the table as a first-line treatment. A new meta-analysis examining 26 randomized controlled trials found that both aerobic and resistance training significantly reduced depressive symptoms—often to a degree comparable with more traditional interventions. Importantly, this effect was consistent across different exercise modalities, suggesting that the type of movement may be less critical than the act of moving itself. Though aerobic exercise is more commonly studied, resistance training is emerging as a potentially underappreciated tool for managing both depression and anxiety. Mechanistically, the antidepressant effects of exercise are rooted in biology: movement rewires mood-regulating circuits through multiple pathways. It helps correct imbalances in the kynurenine pathway—diverting harmful neurotoxic compounds toward neuroprotective ones—while also triggering anti-inflammatory responses and boosting brain-derived neurotrophic factor (BDNF), a key player in neuroplasticity. These molecular changes aren't just theoretical, they're observable in both human and animal studies, and they mirror the changes seen with successful antidepressant use.

Exercise–In All Forms—Reduces Depression and Anxiety

For the latest study on exercise for depression and anxiety, researchers meta-analyzed a total of 26 randomized controlled trials that compared either aerobic exercise, resistance exercise, or combined training to a control intervention—usually a standard of care such as medication, CBT, counseling, or health education.

While both resistance and aerobic exercise were included, a majority of the studies (21) used an aerobic exercise-only intervention, while a measly 3 of them used resistance training and 6 used combined aerobic and resistance exercise…illustrating that we have much more to learn (and more studies to conduct) on resistance exercise as it relates to depression.

Exercise had a large benefit for reducing depressive symptoms, and importantly, this didn't depend on the mode of exercise—both aerobic and resistance exercise reduced depressive symptoms. While aerobic exercise did have a numerically greater effect (a 1.6-point reduction in standardized depression scores) than resistance exercise (a 0.89-point reduction), the difference wasn't statistically significant.

Exercise also helped moderately reduce anxiety symptoms, again with both aerobic (a 0.56-point reduction in standardized depression scores) and resistance exercise (a 0.83-point reduction) showing benefits. This time, resistance exercise had a numerically (but not statistically significant) advantage compared to aerobic exercise, hinting at its potentially greater effectiveness for anxiety outcomes.

Why Exercise Helps with Depression

The claim that "exercise cures depression" is a bold and controversial one.

That's because—despite observational studies showing a link between higher levels of physical activity and lower levels of depression—some argue that this is a classic case of reverse causality. Maybe it's not that physical activity fights depression per se, but rather, that more depressed people just exercise less.

We have to acknowledge that this is a possibility. Adults with major depressive disorder are less active and more sedentary than adults without depression, and nearly 70% of them don't meet the recommended physical activity guidelines, putting them at a much higher risk of cardiovascular disease, metabolic syndrome, and overall mortality. People with depression live an average of 10 years less than people without depression.

Exercising less isn't a matter of laziness or willpower. Depression creates several barriers to participating in physical activity including depressive symptoms themselves which hamper motivation, a higher body mass index and other physical comorbidities that make physical activity challenging, and reduced self-efficacy.

However, two things can be true. Yes, depression creates a landscape less conducive to physical activity, but physical activity per se has also been causally linked to depression. Mendelian randomization studies show that people genetically inclined to be less active tend to have higher rates of depression, suggesting that physical inactivity isn't just associated with—but actually contributes to—depressive symptoms.^[1]

There is also robust mechanistic evidence supporting a link between exercise and depression.

Mechanisms Linking Exercise to Depression

Kynurenine

One biological pathway linking exercise and mental health involves kynurenine—a metabolite produced from the amino acid tryptophan. Under stress and inflammatory conditions, tryptophan metabolism is diverted away from serotonin production toward the kynurenine pathway, resulting in increased formation of quinolinic acid, a neurotoxic compound linked to depression and neurological disorders.

×

Exercise positively modulates this pathway, shifting it toward neuroprotection. Specifically, endurance exercise stimulates muscles to produce higher levels of kynurenine aminotransferase (KAT), an enzyme that converts kynurenine into kynurenic acid rather than quinolinic acid.^[2] Kynurenic acid is neuroprotective and, importantly, cannot cross the blood-brain barrier. This enzymatic shift significantly reduces the availability of kynurenine to form quinolinic acid in the brain, thereby lowering the neurotoxic burden. This "kynurenine hypothesis" has substantial scientific backing. Individuals experiencing depression typically show an unfavorable shift—characterized by elevated ratios of kynurenine to tryptophan and increased quinolinic acid levels. Conversely, experimental studies in animal models demonstrate that enhancing KAT enzyme activity offers protection against stress-induced depression. Furthermore, endurance athletes consistently exhibit higher concentrations of KAT in muscle tissue, supporting exercise's role in promoting mental resilience through this biochemical mechanism.

Inflammation

​​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 vigorous aerobic exercise.

Endocannabinoids and Endorphins

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.

Conclusion

Exercise—particularly when it's high-intensity—is one of the best ways to sharpen thinking and raise one's spirits for several hours.

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.

Most health organizations recommend at least 150 minutes and up to 300 minutes of exercise 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.