Putting the “high” in runner’s high

October 16, 2018

Written by: Sarah Reitz

 

By now we’ve all heard of the seemingly endless benefits of exercise: things like cardiovascular improvements, boosts in energy and mood, and disease prevention, to name a few. But some people experience an extra benefit, a phenomenon commonly known as “runner’s high”. While runner’s high has been discussed for decades, an exact definition was difficult to formalize since it often relied on subjective reports from the runner’s themselves and isn’t even felt by all runners. The lack of an agreed-upon definition made scientifically studying runner’s high a nearly impossible task. After all, how can you experimentally study something when you don’t know what it is? However, this changed in 2004 when a pair of researchers defined runner’s high as a decrease in anxiety (anxiolysis), a decrease in pain (analgesia), an increased sense of relaxation (sedation), and a feeling of euphoria induced by aerobic exercise1.

Wait. Anxiety- and pain-relief, a sense of euphoria, and mild sedation? Is this really from exercise, or were you just hanging out in Eric Foreman’s basement in That 70’s Show (…if you know what I mean)? In fact, research over the past two decades has revealed that the shared symptoms between runner’s high and the use of certain classes of drugs is not coincidence; it’s neuroscience.

 

The Endorphin Hypothesis

When you think of pain-relief, you probably think of drugs like morphine or heroin. These drugs work by binding to and activating opioid receptors in the body, ultimately reducing our sensation of pain. It turns out our bodies can make their own natural (though less powerful) versions of these drugs, referred to as endorphins. When researchers first began examining the biology of runner’s high, they noticed that levels of one specific class of endorphins, called β-endorphins, were increased in the bloodstream following long-distance running2. This made sense: exercising for long periods of time is often uncomfortable or even painful, so our body produces endorphins— literally our body’s own version of morphine — for pain-relief. However, there was one glaring problem with this endorphin hypothesis of runner’s high. Endorphins are very large molecules (Figure 1) and are unable to cross the blood-brain barrier, the tightly packed network of cells surrounding the blood vessels in the brain that acts as a filter between the bloodstream and the brain.

beta
Figure 1: The molecular structure of β-endorphin, a molecule known to increase in the blood after aerobic exercise. The extremely large size of this molecule prevents it from crossing from the bloodstream into the brain. Image via Wikimedia Commons

Therefore, the fact that endorphin levels increased in the blood following a long run in no way means that endorphin levels also increase in the brain. Another strike against the endorphin hypothesis came from a study showing that runners still experienced a runner’s high even after they were given drugs that prevented β-endorphins from activating their opioid receptors3. Luckily for scientists, β-endorphins aren’t the only molecule that is increased in the bloodstream after prolonged exercise

 

The Endocannabinoid Hypothesis

A 2003 study found that levels of anandamide, an endocannabinoid, were increased in the blood following 50 minutes of moderately intense running or biking4. But what are endocannabinoids? Endocannabinoids are a class of molecules that activate the same receptors as THC, the psychoactive molecule in marijuana (their name quite literally comes from the term “endogenous cannabis”). Like endorphins, endocannabinoids also reduce pain in both the brain and body. However, pain relief is not the only sensation that occurs when these molecules activate their receptors. In addition to analgesia, activation of endocannabinoid receptors also produces sedation, reductions in anxiety, and a sense of well-being. Sounds a lot like runner’s high, right?

Since that 2003 study, research continues to support the idea that runner’s high is caused by the same system responsible for marijuana high. First, unlike endorphins, anandamide is a small, fat-soluble molecule that can cross the blood-brain barrier (Figure 2).

anadamide
Figure 2: The molecular structure of anandamide, an endocannabinoid known to increase after aerobic exercise. Unlike the β-endorphin in Figure 1, anandamide is small enough to cross the blood-brain barrier. Image via Wikimedia Commons

Therefore, it is possible for the increased levels of anandamide in the blood to also affect the brain. To test the endocannabinoid hypothesis of runner’s high more robustly, scientists turned to mouse models of runner’s high. In the lab, mice will run on running wheels even when there is no obvious reward for doing so, leading to the belief that they find running inherently rewarding. Additionally, after running, mice show an increased pain tolerance, decreased anxiety, and are less active — 3 of the hallmarks of a runner’s high.

In a series of studies conducted by a group at the University of Heidelberg, increased levels of anandamide and endorphins were seen in the blood of mice who had been running, but not in the blood of control mice who were inactive3. When researchers blocked endorphin signaling prior to running, the mice still showed all of the hallmarks of a runner’s high, suggesting again that endorphins are not the main cause of this phenomenon. However, when researchers blocked endocannabinoid signaling in the mice before running, the runner’s high never came. The mice were just as anxious as they were before their runs, and were equally sensitive to pain, providing strong evidence to support the idea that endocannabinoid signaling is responsible for runner’s high.

 

How Can I Get a Runner’s High?

As mentioned earlier, one of the reasons it’s so difficult to study runner’s high is because it is not an easy state to reach. In both humans and animals who have been studied, the characteristics of a runner’s high only develop after long-distance aerobic exercise. Mice who developed runner’s high in the previous study ran almost 3 miles a day on their wheels — no small feat for such a tiny animal! It’s not only distance that matters; overall exertion is key to developing runner’s high as well. Both humans and dogs show increases in blood levels of anandamide after 45-50 minutes of running (at around 70-80% of maximum heart rate), but not after low-intensity walking for the same amount of time5.

Finally, if you still want to try and achieve a runner’s high it’s important to look at the type of aerobic exercise you are doing. In humans, runner’s high has been reported after running and cycling, but not after activities that involve short, intense bouts of exercise like sprinting or weightlifting. Even activities that involve prolonged periods of aerobic exercise, such as soccer or basketball, don’t produce a runner’s high. This could be due to the fact that these activities involve constantly changing the pace and intensity of the workload, rather than the constant intensity of running or cycling. So, if you want that rush of euphoria and pain-relief: run (or cycle) fast and far! Maybe one day I’ll be able to experience a runner’s high for myself, but until then I’ll just live vicariously through the lucky people who have reached that point.

 

Image References:

Cover Image via Pixabay, CC0 Creative Commons. https://pixabay.com/en/running-runner-long-distance-573762/

Figure 1 via Wikimedia Commons, CC0 Creative Commons. https://commons.wikimedia.org/wiki/File:Beta-endorphin.png

Figure 2 via Wikimedia Commons, CC0 Creative Commons.  https://commons.wikimedia.org/wiki/File:Anandamid.svg

 

References:

  1. Dietrich A & McDaniel WF (2004) Endocannabinoids and exercise. Br J Sports Med 38(5):536-41
  2. Farrel pa, Gates WK, Maksud MG, Morgan WP (1982) Increases in plasma beta-endorphin/beta-lipotropin immunoreactivity after treadmill running in humans. J Appl Physiol 53:1245-49
  3. Fuss J, Steinle J, Bindila L, Auer MK, Kirchherr H, Lutz B, Gass P. (2015) A runner’s high depends on cannabinoid receptors in mice. Proc. Natl. Acad. Sci. U.S.A. 112, 13105–13108
  4. Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A (2003) Exercise activates the endocannabinoid system. Neuroreport 14(17):2209-11.
  5. Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A (2012) Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’. J Exp Biol 215(Pt 8):1331-6. doi: 10.1242/jeb.063677.

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