New link between endocannabinoids and exercise may help in treatment of depression

Summary: Moderate intensity exercise significantly boosts endocannabinoids and improves mood for those with major depressive disorder.

Source: Iowa State University

Researchers know exercise improves mood for people with depression, but there are still questions about exactly how it makes people feel better.

The answers may be found in the endocannabinoid system. The system is made up of the body’s own naturally occurring cannabinoid molecules and their receptors, said Jacob Meyer, an assistant professor of kinesiology at Iowa State University. Activation of these receptors appears to strengthen connections in the brain and may influence pain and depression.

In a new study, Meyer and researchers at the University of Wisconsin-Madison, Medical College of Wisconsin and William S. Middleton Memorial Veterans Hospital, measured endocannabinoid levels and changes in mood before and after exercise sessions with varying levels of intensity. They found a significant boost in endocannabinoids and improvements in mood following prescribed moderate-intensity exercise.

The findings are published in Medicine & Science in Sports & Exercise. Meyer says understanding the link between endocannabinoid levels, mood and exercise could lead to better treatment options.

“Finding alternatives to medication is important for the treatment of depression,” Meyer said. “If we can figure out how exercise works with the endocannabinoid system, we could then design optimal exercise interventions.”

Preferred vs. prescribed exercise

The researchers analyzed data from 17 women with depression. Each woman completed two, 30-minute exercise sessions on a stationary bike—one at a prescribed moderate intensity and a second of the participants’ own preferred intensity. Both sessions improved mood, but the researchers only noted an increase in endocannabinoid levels for moderate intensity exercise. There was no difference for preferred intensity.

This shows a person walking in the sun
According to the Institute of Medicine, people with less than 20 nanograms of vitamin D per milliliter of blood are deficient. The Endocrine Society set a higher threshold of 30 nanograms. Neither guideline is more definitive than the other at this time. The image is credited to Iowa State University.

Meyer says this was surprising, but the differences may stem from variation in the preferred session. For example, some women stayed consistently at a lighter intensity, while others completed intervals. With a small sample, the variation may have obscured the relationship between the preferred intensity and change in endocannabinoids, Meyer said.

The findings are consistent with a 2016 study, in which Meyer and his colleagues looked at the effect of exercise on brain-derived neurotrophic factor or BDNF, a protein that regulates neuron growth and survival. People with depression typically have lower levels of BDNF. The 2016 study found that when women with depression were prescribed an exercise session similar in intensity to one they selected, their BDNF levels were significantly higher following the prescribed session.

“Having someone else prescribe the exercise could be involved in both the psychological and biological response to exercise,” Meyer said.

Effects appear to be long-lasting

For each exercise session, researchers collected blood samples immediately after exercise and also measured mood and anxiety at 10 minutes and 30 minutes post-workout. Changes in endocannabinoids were significantly related to the improvement in mood up to 30 minutes after the moderate exercise, suggesting that the system contributes to the mood-enhancing effects of prescribed exercise, Meyer said.

“These results show us that the effect of prescribed moderate-intensity exercise on mood is generally pretty quick and lasts for a while at a relatively sustained rate,” Meyer said. “However, given that people felt better after the preferred exercise session, even though it didn’t change endocannabinoid levels, multiple factors are likely involved in how exercise makes people feel better.”

That is the focus of Meyer’s ongoing Exercise and Brain Health Study. The goal is to develop new treatments for mental health conditions that include exercise. Meyer is currently recruiting 20-to-60-year-old men and women to participate in the study.

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About this neuroscience research article

Iowa State University
Media Contacts:
Angie Hunt – Iowa State University
Image Source:
The image is credited to Iowa State University.

Original Research: Open access
“Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder”. JACOB MEYER; KEVIN CROMBIE; DANE COOK; CECILIA HILLARD; KELLI KOLTYN;.
Medicine & Science in Sports & Exercise. doi:10.1249/MSS.0000000000002006


Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder

The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults.

We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states.

Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise.

Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen’s d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB–mood relationships were not found for PREF.

Given the broad, moderate–strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.

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