The Real “Runners’s High”: Exercise, Cannabinoids, and Depression

About 3 in 10 people will suffer from major depressive disorder (MDD) throughout their lifetime. We don’t know why exactly (biologically, that is) and this results in a fairly poor treatment strategies that sometimes fail to work. Medications, cognitive behavior therapy, psychotherapy, counseling — we throw all of these at depression in hopes of helping individuals who suffer from this condition. Without knowing the underlying biological cause, however, we can’t for sure know which treatment will work best for certain individuals.

It is well known exercise can consistently improve mood and well being in adults and has a significant anti-depressant effect in people with MDD. Those who engage in physical activity display better health outcomes, quality of life, and mood. Chronic training and even an acute (single) bout of exercise improve mood for certain lengths of time.

I (and probably you) have experienced this personally. Depending on the workout, an aura of post-exercise good feelings can surround me for an entire day. This is commonly referred to as the “runners high” — a feeling of euphoria commonly felt during and or after exercise.

We don’t really even know the mechanisms as to how exercise improves mood. Some have claimed that endorphins are to blame (or rather, thank) for runners high, but studies show this theory has limited support.

If we do know the precise pathways that exercise is beneficial, it might be prescribed to certain people in certain waysto treat MDD or even to enhance mood in normal healthy people. In some cases, it already is. Studies have shown that exercise is just as effective as medication for the treatment of depression. Give them a pill…or give them a pair of Nikes.

Can we manipulate the runners high to boost human health?

Enter the popular (and controversial) area of cannabinoids. You’ve probably heard of cannabidiol (CBD) and all of the miracles it performs — the New York Times thinks it might just be a “fix for our anxious times.” Truth be told, this compound (a phytocannabinoid found in the cannabis plant) is in the early stages of investigation. It might hold promise, but it’s too early to tell.

However, the system that is targeted by CBD, the endocannabinoid system (eCB) is known to be involve in MDD. Two endocannabinoids: 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (anandamide; AEA) bind to CB1 and CB2 receptors throughout the brain and nervous system, exerting various effects.

Brain endocannabinoid System

Circulating eCBs are lower in people who are depressed vs. healthy adults. If you knock out the eCB system in mice or block it with certain drugs, this causes depressive-like behavior. This suggests the eCB system is involved in some of the mood-dampening effects associated with MDD and other cognitive disorders.

It is a fact that exercise boosts eCB concentrations in the body of humans (and dogs). For this reason, it can be theorized the improvements in mood after exercise might be related somehow to the eCB system. Could this be the secret to the “runner’s high” and the anti-depressant like effects of physical activity? Does exercise give us a neurobiological eCB “reward” that encourages us to continue? Does perhaps a lack of physical activity contribute to less reward and hence, less “good feelings”?

Multiple studies have reported exercise-induced increases in eCB are associated with improvements in mood in healthy adults. Exercise increases circulating eCBs which are associated with increases in positive affect and decreases in depression, tension, and mood disturbances. One study in adults with post-traumatic stress disorder (PTSD) observed that increased 2-AG (eCB) following exercise was related to a decrease in negative mood states and reduced pain.

The consistent positive associations of eCB and mood all point to a theory. In people with MDD, exercise might have the same mood-enhancing effects. A recent study titled “Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder” put this theory to the test.

Researchers compared the mood and eCB responses following two types of exercise — a moderate intensity and a “preferred intensity” in women (avg. age 40) with self-reported diagnosed MDD. Two questions were asked.

First, does acute exercise change levels of eCBs in the blood?

Second, are the changes in eCBs following exercise related to changes in mood states?

After filling out some baseline assessments (to measure mood), participants underwent one of the two exercise sessions in a random order. Each included 30 minutes of exercise at either a moderate intensity (perceived exertion of 13 on a scale of 6–20) or a preferred intensity (i.e. no prescription). After exercise (10 and 30 minutes later), more mood questionnaires were filled out and a blood sample was taken so that variables on interest could be analyzed later on.

Self-reported measures (to assess mood) included the Beck Depression Inventory-II, a 65-item Profile of Mood States (POMS) and a State-Trait Anxiety Invensity (STAI) which the women completed before and after each session (with the exception of the BDI, which was only done before). Using these , it’s possible to assess things like depression, tension, confusion, fatigue, vigor, and anger as well as mood disturbances in response to exercise.

The goal of the study was to relate the changes in these mood scores and questionnaires to the quantifiable changes in circulating compounds (eCBs and three relevant lipids referred to as PEA, OEA, and 2-OG).

What happened to mood? After both exercise sessions, mood states improved — tension, depression, anger, fatigue, confusion — each was lower after exercise compared to baseline. In contrast, vigor (a positive emotion) increased. The total mood disturbance and state-anxiety scores also improved (decreased) at 10 and 30 minutes post-exercise.

Results for changes in mood following exercise

Interestingly, it didn’t matter whether moderate or “preferred” intensity was performed — mood improved equally after both exercise conditions. It is also interesting that the intensity was virtually the same for both conditions. Heart rate, perceived exertion, and energy expenditure were the same in preferred vs. moderate exercise. This is likely important, since exercise intensity plays a key role in the robustness of the eCB, mood, and hormone response to exercise.

What about the endocannabinoids? Moderate intensity exercise led to an increase in the eCB AEA from pre- to post-exercise, along with the related lipid OEA. Other than that, no changes were seen in the other eCB (2-AG) or lipids.

Results infer that some of the positive changes in mood may be related to eCB concentrations. The magnitude of change in eCB for the moderate session was associated (negatively) with several of the mood variables.

10 minutes after exercise, a greater increase in AEA was associated with a greater decrease in depression, confusion, fatigue, mood disturbance, and state anxiety. An increase in 2-AG, the other eCB studied, was also associated with greater improvement in depression and confusion. 30 minutes after exercise, the same negative correlations were found between AEA and confusion, mood disturbance, and state-anxiety and for 2-AG, confusion and total mood disturbance.

Surprisingly to me (and perhaps the researchers), the preferred intensity session led to no significant changes in any eCBs or lipids, and no associations between the change in eCBs and changes in mood, despite the intensity and duration being nearly identical to the moderate session.

Effect size for changes in eCBs and lipids after exercise

The main takeaway of the current study is that in women with major depressive disorder, moderate aerobic exercise (but not preferred intensity) leads to increases in circulating endocannabinoids (AEA) and that increased eCBs are related to improvements in mood which last for up to 30 minutes post-exercise. Whether these effects are maintained for longer, we don’t know, since 30 minutes was the maximum time point studied. I’d imagine the positive mood would last at least a few hours.

Why didn’t eCBs change following preferred intensity exercise, despite positive changes in mood? The authors hypothesize that since participants could freely manipulate how hard they cycled (compared to maintaining “steady state” in the moderate group), this might have led to a wide variability of intensity among participants and within each session.

Even though intensity was the same for the moderate and preferred groups overall, some participants might have exercised harder, and some not as hard as others when they could choose their own speed. This might “mask” any significant changes that occurred. In research studies, the “average” of the data is just that, the average. If you have a lot of people increasing and a lot of people decreasing in something (say, eCBs), the average falls somewhere in between, appearing as “no change.” Maybe half of the group had increased eCBs while the other half had decreases? This we don’t know.

Despite this fact, mood still changed in both protocols. This means that eCBs might just be one piece of the puzzle explaining the mood-enhancing effects of exercise. In the words of Peter Attia, they’re likely “sufficient, but not necessary” for the exercise-induced mood boost.

This “sufficient but not necessary” concept is illustrated in a statement I came across when reading a paper questioning the role of endorphins in the runners high. We must remember that one neurotransmitter or even a single system is unlikely to explain states of consciousness (say, euphoria following exercise). Interactions among neural circuits and day-to-day changes in your own experience, external situations, and even relationships will converge and interact. This, in turn, will influence our emotional response to exercise.

Basically — exercise isn’t the ONLY variable involved in mood.

Sure, I feel good MOST days after I workout. But some days, I don’t. This is likely because other mechanisms in my body and the world around me dictate my overall mood, not just the internal release of brain chemicals. One factor — an important one at that — among many other important factors.

Nevertheless, this study provides more data on the ability of exercise to improve mood — improve life. Exercise is indeed medicine, and the more we learn about its powerful effects throughout the human body, the more we can harness its potential for our own good.

CBD has been shown to have some anti-anxiety properties and might be effective for pain management, but more research on this compound needs to be done in the future; the same goes with THC. But if going for a run, ride, or a swim can have the same effects on the endocannabinoid system along with hundreds of other physiological benefits, it seems like exercise is just what the doctor should order.

References

Meyer JD, Crombie KM, Cook DB, Hillard CJ, Koltyn KF. Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder. Med Sci Sports Exerc. 2019;

Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456–73.

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Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF. Psychobiological Responses to Aerobic Exercise in Individuals With Posttraumatic Stress Disorder. J Trauma Stress. 2018;31(1):134–145.

Brellenthin AG, Crombie KM, Hillard CJ, Koltyn KF. Endocannabinoid and Mood Responses to Exercise in Adults with Varying Activity Levels. Med Sci Sports Exerc. 2017;49(8):1688–1696.

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Blumenthal JA, Babyak MA, Doraiswamy PM, et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007;69(7):587–96.

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PhD candidate at the University of Florida — Science writing with a particular focus on exercise and nutrition interventions, aging, health, and disease.

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