Last summer was full of sports, starting with the UEFA Euro in France and carrying on with Olympics and Paralympics in Rio. It’s a lot of fun to watch sports, but it’s even more fun to do sports yourself.

Remember this amazing feeling when you’re finishing your run and you feel like you’re on top of the world? Most likely, what you experienced was ‘runner’s high’ – a euphoric feeling during physical activity, that often comes with a surge of energy. Many people also say they feel somewhat more relaxed and less anxious, and even forget about pain³. Although it’s called ‘runner’s high’, not only running can elicit this – any kind of intense aerobic exercise can result in it³.

So, why does it happen at all? What happens in your body when you experience runner’s high, and, in particular – what happens in your brain? Can this effect be even beneficial in the long run (pun intended)? All these are the questions were in the spotlight of many recent studies^1–3, ^6–7, and I will try to give an overview of the answers to them in today’s blog post.

Why does a runner’s high happen?

Evolutionarily, such a system makes sense: most likely it has developed as a way to keep archaic humans chasing their dinner – wounded prey, or, run away from becoming a dinner for predators². However, this is not unique to humans. Another reason why humans needed such an adaptation was for a social purpose: to spread the news². As known from the history, the first marathon runner was a Greek messenger Philippides, who ran from the Battle of Marathon to Athens to report the victory.

What happens in your body?

Opioids vs endocannabinoids

The main theories on the physiology of the runner’s high are based on the increase of two chemicals in the blood: beta-endorphin, which is an opioid, and anandamide – an endocannabinoid^1,3. One might have heard these names in a different context – and yes, they belong to the same groups of chemicals as some addictive drugs.

However, until recently, it was not quite clear what role each chemical plays in the runner’s high. In a recent study by Johannes Fuss and his colleagues³, scientists managed to disentangle the effects of opioids and endocannabinoids. To do so, they set up rat races (well, to be exact, they made mice run) – a nice insight into studying human phenomena in animal models. In this case, mice were needed because one can do genetic manipulations with them.

Researchers took two groups of mice: one group ran about 6.5 km in a wheel spread across six days (considering the size of the animals, it’s quite a lot!), and the other was a control group with no special running regimen. First, the researchers wanted to see if running made mice less anxious. How can you test anxiety in mice when you can’t ask them? Do they bite their nails? Actually, there is a special test: the so-called ‘dark-light box test’. Mice are nocturnal animals and don’t like spending time in bright light, but rather prefer staying in dark cozy corners. So if they spent more time in bright areas, they feel less anxious.  It turned out, that the runner mice spent more time in bright light than their less athletic brothers and sisters, an indicator that runner mice felt less anxious³.

Another effect of the runner’s high is reduction of pain¹. To test this, mice were placed onto a hot plate, and scientists counted how long they could stand the high temperature before they licked their paws or jumped (don’t worry, the temperature of the plate was just 53 °C). Again, runner mice could tolerate heat longer than their less sporty counterparts. Interestingly, runner mice were less active after the tests than the control group. Researchers interpreted this as a sign of sedation, which is also sometimes mentioned as a feature of a runner’s high¹. But if mice were just tired? It’s hard to tell just from the mice behavior (what a pity mice can’t talk!)³.

In the second part of the study, researchers measured the level of endocannabinoids in blood plasma and found elevated levels in the runners’ bunch. Okay, but maybe previously observed effects were due to opioids, while endocannabinoids just happened to increase simultaneously? To disentangle the effects of endocannabinoids and endorphins, researchers took advantage of pharmacological manipulations. Before running, mice were injected with chemicals that reduce the efficacy of either endocannabinoids or endorphins. After the run, only mice with blocked endocannabinoid receptors did not show reduction of anxiety. These mice also reacted slower in the hot plate test, unlike the mice with blocked endorphins. This shows that it’s actually endocannabinoids that are crucial for pain reduction.³

Back to the sedation question: researcher noticed that mice with endocannabinoids blocked did not run longer after the tests, so probably mice moved less in the first experiment just because they were exhausted.³

To double check how one of the endocannabinoid receptors is involved in the anxiety reduction, researchers used mice that lack receptor that is sensitive for endocannabinoids. As expected, mice that were genetically insensitive to endocannabinoids did not show any anxiety-reduced behaviour after running. This is another argument in favor of the role of endocannabinoids in runner’s high.³

Researchers, unfortunately, did not find a way to test euphoria in mice³ (there are disadvantages in animal models as well!), so the exact mechanism of this component of runner’s high is yet to be found. Perhaps, it’s the contribution of opioids.

Benefits of aerobic exercise for mental health

Okay, get back from mice to humans. So what are the benefits of running and initiating all these chemicals flowing around? We all know how exercise is important for our health, that’s no news. However, does this also translate to our mental functioning? Research clearly indicates that regular exercise is linked with better cognitive function. It has also been shown that it can slow down the cognitive decline observed in neurodegenerative disorder such as Alzheimer’s disease or dementia⁴. The following sections review possible neurophysiological mechanisms of underlying the positive effects of exercise on our mind.

Brain Derived Neurotrophic Factor

It looks like the increase of endocannabinoid anandamide triggers the increase in Brain Derived Neurotrophic Factor (BDNF). BDNF is a very important substance – it is involved in the generation of new neurons and synapses, which is in turn, important for memory and learning processes. In elderly, the neurogenesis is slowed down; one study showed that in 50-80 year-old people BDNF increased even after systematic moderate-pace walking. Although it didn’t lead to the improvement of cognitive skills, at least there was no decline, as in sedentary control group⁵.

In a recent study with mice, it has been shown that running promoted the development of dendrites (branches of neurons that collect information from other neurons) in neurons in the hippocampus⁶. Hippocampus is a brain area that is heavily involved in memory formation and other cognitive tasks, such as spatial navigation, but also in emotional regulation. A recent behavioural study⁷ also showed that after exercising people were better at regulating their emotions, and even more so after running (an aerobic exercise) as compared to stretching.

Dopamine

Exercise has a positive effect on mood in depressed people^3,10. It appears to be linked with one of the signalling chemicals of the nervous system, the neurotransmitter dopamine, which is also affected by exercise. Increase of endocannabinoids after exercise induces rise of the dopamine concentration in the nucleus accumbens, a part of the brain that is involved in reward signal processing⁸. Therefore, dopamine is also thought to contribute to the pleasant feeling of a runner’s high³.

Cortisol

Exercise can also be helpful for stress management. Psychological stress has a bad reputation as it can trigger anxiety or listlessness. Intense aerobic exercise can also be viewed as physical stress (more on stress read in Antje’s article), and it triggers a physiological stress response, such as the rise of ‘stress hormone’ cortisol. So why is it then that one stressor is good for us, and another – not so much?

The stress responses to both are quite similar – cortisol is also released after exercise, and the more you exercise, the more is released. However, after physical stress cortisol is pretty quickly converted into its harmless version, whereas it is not the case in chronic psychological stress. In the long run, cortisol is potentially harmful and even toxic for your neurons⁹. So it’s good to keep it down-regulated by exercising!

Take-home message

Long-term benefits of aerobic exercise for your body are obvious, unlike the benefits for your brain and mind. Summing up, here’s a brief list of the ones reviewed in this blog post:

• Less anxiety;
• Better cognitive function;
• Slowed down cognitive decline;
• Better emotional regulation;
• Better mood;
• Better down-regulation of stress hormone cortisol.

If this sounds appealing to you and after reading this blog post you feel a strong urge to go for a run, then my mission is achieved. To be honest, one of the reasons why I decided to write a blog post on this topic was to start running again myself. And finally, after a four-year break, I use my running shoes for their original purpose.

P.S. Please share your experience with us in the comments below if you actually did go for a run!

References:

1. Heijnen, S., Hommel, B., Kibele, A. & Colzato, L. S. Neuromodulation of aerobic exercise-A review. Frontiers in Psychology 6, 1–6 (2016).
2. Schulkin, J. Evolutionary Basis of Human Running and Its Impact on Neural Function. 10, 1–10 (2016).
3. Fuss, J. et al. A runner’s high depends on cannabinoid receptors in mice. 6–11 (2015). 
4. Brown, B. M., Peiffer, J. J. & Martins, R. N. Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer’s disease? Mol. Psychiatry 18, 864–74 (2013).
5. Leckie, R. L. et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front. Hum. Neurosci. 8, 1–12 (2014).
6. Dostes, S. et al. Running per se stimulates the dendritic arbor of newborn dentate granule cells in mouse hippocampus in a duration-dependent manner. Hippocampus 26, 282–288 (2016).
7. Bernstein, E. E. & McNally, R. J. Acute aerobic exercise helps overcome emotion regulation deficits. Cogn. Emot. 9931, 1–10 (2016).
8. Cheer, J. F. et al. Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation. J. Neurosci. 27, 791–795 (2007).
9. Kaminska, M., Harris, J., Gijsbers, K. & Dubrovsky, B. Dehydroepiandrosterone sulfate (DHEAS) counteracts decremental effects of corticosterone on dentate gyrus LTP. implications for depression. Brain Res. Bull. 52, 229–234 (2000).
10. Gardner, E.L. Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol. Biochem. Behav., 81, 263-284 (2005).