Quick Study Analysis: What Causes the Runner's High?
tl;dr: Getting to the bottom of food addiction and obesity.
One of the best reasons to run, and there are many, is the runner’s high. It’s that feeling of euphoria that one feels after running for a short time. (I should add that it helps to run regularly, as if you are out of shape you are likely to feel pretty dreadful at first.)
Virtually all runners, if you ask them, will tell you that this high is due to endorphins, and perhaps make the comment that this is why running can be so addictive: it’s like heroin, but with out the negative side effects.
Another Medical Myth
It turns out that this is another medical myth.
Much research, in animals and humans, has made it clear that endorphins, which are opioids produced by your body (endogenously) are not responsible for this effect. These are substances similar in effect to morphine and other opiate drugs derived from the opium poppy. Instead, it is the endocannabinoid system (ECS) that controls the desire for exercise and the experience of the runner’s high. Endocannabinoids are chemicals with similar effects to the THC contained in marijuana.
The endorphin hypothesis was poorly supported by evidence, although it was widely perpetrated by the media. (Siebers, 2023)
That sounds familiar.
The Real Driver
“Do Endocannabinoids Cause the Runner’s High? Evidence and Open Questions” (Siebers, 2023)
This is a review article, but it covers a variety of experiments that have been performed over the last few decades. It deserves a close reading, but this is supposed to be quick, so I’m just going to hit some highlights. But first, here’s a basic difference between the ECS and endorphin systems.
This is an over-simplification of these two areas. However it makes clear a signature effect of drugs that block the ECS: they prevent appetite for things, including opiate drugs.
“Additionally, AM6527 dose-dependently inhibited heroin self-administration under both fixed-ratio and progressive-ratio reinforcement schedules and oral sucrose self-administration under a fixed-ratio reinforcement schedule, as well as cocaine- or heroin-triggered reinstatement of drug-seeking behavior in rats.” (Soler-Cedeño, 2024)
Note the effect on sugar (sucrose) intake. Regarding the runner’s high, it was demonstrated in humans in 2021 that the effect is not derived from endorphins.
The right-hand graph shows that the Ω-6 fat arachidonic acid (ADD or AA) is increased in blood. This is notable as AA is a precursor for both AEA and 2-AG (the two left-hand graphs), which are the two primary endocannabinoids for the promotion of appetite, and also for inflammatory mediators of the sort that are essential for healing and growth after acute exercise.
Naltrexone (which blocks the opioid receptors, thus preventing the endorphins from having an effect), had no effect on the runner’s high: “Opioid blockade did not inhibit anxiolytic effects or euphoria after running. Also, the release of eCBs [endocannabinoids] was not prevented by opioid blockage after running and walking. In conclusion, this study suggests that the runner’s high does not depend on endorphins” (Siebers, 2023). (“Anxiolytic” refers to a decrease in anxiety.)
By 2021, there was no human-approved drug that could be used to block the ECS, as Rimonabant had been erroneously withdrawn, and nothing had taken its place. Earlier work in animals had compared the effects of ECS and endorphin blockade, and had determined that, “both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse.” (Rasmussen, 2011)
A later study confirmed this result, “We thus show for the first time to our knowledge that cannabinoid receptors are crucial for main aspects of a runner’s high.” (Fuss, 2015)
“In a series of experiments, we were able to show that the reduction in anxiety-like behavior after acute long-distance running depends on CB1 receptors on forebrain GABAergic neurons. Pain reduction, in contrast, depends on peripheral CB1 and CB2 receptors. Our data demonstrate that an intact eCB system is crucial for a runner’s high in mice.” (Fuss, 2015)
The Bliss Hormone
Siebers and co-authors in 2023 note that of the two Ω-6 endocannabinoids they examined, it was AEA that seemed to have the notable effects (with the significant caveat that they were only looking at blood levels, and this may not be sufficient). AEA is the acronym for anandamide, which “…was coined from the Sanskrit word "ananda," meaning bliss, and from the chemical nature of the compound” (Devane, 1992).
“Thus, this study suggests that the experience of positive emotions may somehow be necessary to release eCBs. Furthermore, the study indicates that other activities than endurance sports can activate the eCB system.” (Siebers, 2023)
They’re referring to the fact that women in a choir showed an increase in these hormones when singing, but not when forced to run for the experiment. Evidence for my claim that you may not enjoy the runner’s high until you start to enjoy running!
Anandamide is one of the best examples of naming I’ve encountered in biology.
Exercise Addicts Aren’t Getting Their Fix
Interestingly, people who are addicted to running may have a defective ECS.
“Strikingly, lower AEA levels at all time points in the exercise-addicted group compared with the control group were found. Running did elevate AEA levels in the control group, only. Within the exercise-addicted group, withdrawal of exercise increased depressive mood symptoms, fatigue, confusion, anger, and a loss of vigor. Because of these results, Antunes and colleagues hypothesized that individuals with exercise addiction might have a dysfunctional eCB system.” (Siebers, 2023)
Or they may just be acclimated to it. But it does begin to give us a better understanding of what determines addiction.
Conclusion
This is a follow-up of sorts to my obesity post:
“Overall, the present experiments indicate that administration of both exogenous [THC from marijuana] and endogenous cannabinoids [AEA] selectively induces overeating by stimulating those systems which normally control feeding.” (Williams & Kirkham, 2002)
I read many accounts of people claiming that “food addiction” doesn’t exist, and that people are only eating themselves to obesity because they are gluttons.
I don’t think we can solve the obesity epidemic until we start to address the root causes, and understanding that obesity is the result of an addictive process, and acknowledging what is causing the addiction is a necessary first step.
References
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992). Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor. Science, 258(5090), 1946–1949. https://doi.org/10.1126/science.1470919
Rasmussen, E. B., & Hillman, C. (2011). Naloxone and Rimonabant Reduce the Reinforcing Properties of Exercise in Rats. Experimental and Clinical Psychopharmacology, 19(6), 389–400. https://doi.org/10.1037/a0024142
Siebers, M., Biedermann, S. V., & Fuss, J. (2023). Do Endocannabinoids Cause the Runner’s High? Evidence and Open Questions. The Neuroscientist, 29(3), 352–369. https://doi.org/10.1177/10738584211069981
Soler-Cedeño, O., Alton, H., Bi, G.-H., Linz, E., Ji, L., Makriyannis, A., & Xi, Z.-X. (2024). AM6527, a Neutral CB1 Receptor Antagonist, Suppresses Opioid Taking and Seeking, as Well as Cocaine Seeking in Rodents Without Aversive Effects. Neuropsychopharmacology, 49(11), 1678–1688. https://doi.org/10.1038/s41386-024-01861-y
I guess David Brown has beat the arachidonic acid drum and it's endocannabinoid pathways regarding overeating and obesity. Do runners head for the smorgasbord?