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The Mood-Boosting Power of Exercise: Why Aerobic Exercise is an Effective Antidepressant

Antidepressant Effects of Aerobic Exercise

Do you ever feel like you need a mood boost? If so, you’re not alone. According to the National Institute of Mental Health, one in six Americans takes antidepressants. While antidepressants are an effective option for 40 to 60 percent of individuals in treating depression, they are often associated with adverse side effects. The lack of uniformed effectiveness in combination with unfavorable side effects warrants novel therapies to effectively manage symptoms of depression.


Depression is clinically characterized by a low mood, fatigue, anhedonia, and impairments in cognition. It has a relatively heavy burden on individuals, families, and society. The World Health Organization once showed that ~350 million people were currently suffering from depression, and the disease may last for years.

Aerobic exercise has recently emerged as a promising first line therapeutic to efficaciously treat depression. A 2021 Review posted in Frontiers in Psychiatry found that moderate intensity-aerobic exercise as the primary treatment or adjuvant therapy conferred clinically significant effects depressive symptoms.

Mechanism of Action:

The neuromodular underpinnings of aerobic exercise can be partitioned into 4 neurophysiological components.

  • Normalization of HPA feedback
  • Enhanced BDNF synthesis
  • Endogenous Endocannabinoid’s
  • Bioavailability of Serotonin/Dopamine

HPA Axis:

The hypothalamic-pituitary-adrenal (HPA) axis is the key physiological system that governs the stress response. Impairments in HPA axis homeostasis has been implicated as a major pathophysiological factor in depression. Moderate-Intensity Aerobic exercise has demonstrated its ability to paradoxically increase the stress hormone cortisol, which occurs secondary to increased activation of the HPA axis. However, research has also shown that exercise has the unique ability to simultaneously augment the inactivation of cortisol. What makes physical stress different from psychological stress is this increased inactivation of cortisol into cortisone, this inactivation is not seen with psychological stress.

Aerobic exercises ability to normalize this axis and feedback inhibition can have significant impacts on depressive symptoms.


Brain Derived Neurotrophic Factor (BDNF) exerts beneficial effects on cognition and overall mood through its ability to enhance neurogenesis, synaptic plasticity and long-term potentiation, which is the basis of learning and cognition. Impairments in neuroplasticity have been implicated in Major Depressive Disorder leading to instability of the Default Mode Network. Aerobic based exercise has the ability to enhance BDNF synthesis. A recent review found that a single session of aerobic based exercise lead to BDNF amplification and that this was dose-dependent response, meaning that frequent aerobic training has the ability to magnify this increase.

Endogenous Endocannabinoids:

The positive affect that occurs following aerobic exercise has traditionally been attributed to enhanced beta-endorphin production. However, recent publications have demonstrated that increased endocannabinoid production plays a causal role in the mood enhancing effects of aerobic exercise. More specifically, the increase of the endogenous endocannabinoid anandamide seems to confer these beneficial effects on mood.


Serotonin and Dopamine are two neurotransmitters that have been implicated in depression. Moderate and High-Intensity aerobic exercise has been shown to inhibit competitive inhibition of serotonergic/dopaminergic precursors while concurrently enhancing enzymatic activity leading to increased concentration of these neurotransmitters.

Final Thoughts:

Aerobic exercise in my opinion is an underutilized, efficacious therapy for the treatment of Depressive disorders.

Dr. Tanner Wilson, DC, IFMCP is the founder of EvoHealth Kansas Functional Medicine. His practice focuses on implementing lifestyle, dietary, and evidence-based supplementation interventions to effectively manage chronic disease conditions.

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