Runner's high
Aerobic Physical Exercise

Author: mirko furnari
Date: 12/12/2013


What is the runner’s high?

With the term runner's high we refer to the feeling of euphoria that runners (and many other athletes) feel during or after a strenuous and long physic exercise.
Before there were performed researches about it, this condition was mainly ascribed to psychological causes instead to neurochemical ones.
The runner's high was defined as an intense impetus of euphoria, often compared to the ”trip” induced by some drugs.

For others it’s only a legend. It’s true that run evokes feelings of fulfillment, but maybe the only feeling of that runners is limited to the relief of crossing the finish line.
For years, there has been an attempt to throw light on this phenomenon, with the hope to find a biochemical explanation for this sensation.

In the 2008 some researches proved the link of this feeling with the release of endorphins by the anterior lobe of hypophysis during a long physical exercise.

Endorphins ("endogenous morphine") are endogenous opioid peptides that function as neurotransmitters. They are produced by the pituitary gland and the hypothalamus in vertebrates during:

  • exercise
  • excitement
  • pain
  • spicy food consumption
  • love
  • sexual activity

Endorphins are polipeptids of variable length. Are known three types of endorphins:

  • the α-e., formed by 11 amino acids;
  • the β-e., formed by 31 amino acids and
  • the γ-e., formed by 16 amino acids

They resemble the opiates in their abilities to produce analgesia and a feeling of well-being.
The term implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation.
It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean "a morphine-like substance originating from within the body."

Runner’s high: endorphins, or not endorphins, this is the question

The 80’s

Previous research on the role of endorphins, in producing a runner's high, included trying to understand the mechanisms at work; that data seemed to demonstrate that the "high" comes from completing a physical challenge rather than as a result of exertion. Studies in the early 1980s cast doubt on the relationship between endorphins and the runner's high because when an endorphin (μ-opioid) receptor antagonist was infused (e.g., naloxone) or ingested (naltrexone), the same changes in mood state occurred as when the person exercised with no blocker.


A 2003 study found that a runner's high might be caused by the endocannabinoid, anandamide.
The authors suggest that the body produces anandamide to deal with prolonged stress and pain from strenuous exercise, similar to the original theory involving endorphins.
However, this study did not report the cognitive effects of a runner's high; which seems to suggest that anandamide release may not be significantly related to runner's high. Neurotransmitter, Anandamide which has a structure very similar to that of tetrahydrocannabinol [THC], is the active constituent of cannabis.
This is the "morphine-like" brain molecule.
Morphine mimics the brain's molecule, and therefore has a similar effect. Anandamide is a short-lived, fragile molecule, and does not produce a dramatic natural high, unlike a surge of endorphins, or dopamine. The presence of Anandamide is detected in chocolate. Levels of Anandamide are found to be elevated in schizophrenics. During the sports, (running or physical activity) CB1 receptors are activated by Anandamide.


But it was in 2008 that researchers did the more important discovery.
Few years ago, the only way to check the presence of endorphins in the brain was to do a spinal tap, but it was impossible to put athletes through this test before and after physical exercise.
This problem was overcome, when, in the 2008, a group of German researchers published a document in the magazine Cerebral Cortex, declaring to have found a method for measuring endorphins’ level before and after physical exercise.

To show this, they used a technique called positron emission tomography (PET). For those who don’t know, PET works by injecting a radioactive tracer molecule into the blood. When this tracer undergoes radioactive decay it releases a positron that shoots out and can be detected. By putting the person’s head in a special detector, the direction of the emitted positrons can be used to triangulate their origin in the brain. This allows the scientists to determine the relative concentration of the tracer at different points inside the brain.

At this point the selection of the tracer becomes very important.
It could be used a tracer that just equilibrates throughout the brain, but it would be found nothing important. Instead it is used a tracer whose relative concentrations are modified by brain activity or metabolism.

Examples include radioactive glucose molecules that can become concentrated in brain areas that are metabolically active.
The tracer used in this experiment is a drug that binds non-specifically to opioid receptors. (There are actually three different types of opioid receptors, and this drug does not attempt to distinguish them.)
The ligand is called 6-O-(2-[18F]fluoroethyl)-6-O-desmethyldiprenorphine ([18F]FDPN).
The radioactive isotope for this tracer is an atom of 18F which will decay and release the positron. (This is a pretty common isotope to use in PET because fluorine can be substituted for a hydrogen in whatever molecule you would like to use.)

The theory for how this works is that the tracer binds to opioid receptors in the brain.
Then as endogenous opioids like endorphins are released, they displace the tracer from those receptors leading to a relative reduction of the concentration of tracer — and hence positrons emitted — from that part of the brain.

Key point here: endorphin release in this experiment are measured as reductions in the tracer signal.

The authors measured the resting endorphin activity in the brains of 10 athletes using this system. They then sent the runners out on a 2 hr run. After they returned they put them back in the scanner and looked at endorphin activity again. They compared the images before and after the run to look for what areas of the brain had greater endorphin activity (less signal from the tracer). This produced a list of several brain regions that had increased endorphin activity

Then they asked the subjects to rate how euphoric they felt. They correlated the feelings of euphoria with the changes in the regional activity to find which regions correlated best with euphoria.
They found that several regions increased endorphin activity during exercise and correlated with reported feelings of euphoria:
Changes in central opioid receptor binding after 2 h of long-distance running were identified preferentially in prefrontal and limbic/paralimbic brain regions. Specifically, the perceived levels of euphoria were inversely correlated with opioid binding in prefrontal/orbitofrontal cortices, the anterior cingulate cortex, bilateral insula, and parainsular cortex, along with temporoparietal regions. (Emphasis mine.)x
These results are depicted below for (starting from the top) the anterior cingulate (ACC), the orbitofrontal cortex (OFC), and the insular cortex (INS).

On the right shows the changes in activity.
On the left shows the correlation between changes in signal among the subjects and reported euphoria; see how the two are inversely correlated.

The regions that they found activated during the runner’s high are not all that surprising. Many of these regions, particularly the OFC, have been implicated in perception of reward in many other contexts.
Boecker, H., Sprenger, T., Spilker, M.E., Henriksen, G., Koppenhoefer, M., Wagner, K.J., Valet, M., Berthele, A., Tolle, T.R. (2008). The Runner’s High: Opioidergic Mechanisms in the Human Brain. Cerebral Cortex


Despite the 2008 results published in Cerebral Cortex, in the 2012 a study argued implicitly that endocannabinoids are, most likely, the causative agent in a runner's high, while also arguing this to be a result of the evolutionary advantage endocannabinoids provide to endurance-based cursorial species. This largely refers to quadruped mammals, but also to biped hominids, such as humans. The study shows that both humans and dogs show significantly increased endocannabinoid signaling following high intensity running, but not low-intensity walking. The study does not, however, ever address the potential contribution of endorphins to a runner's high. However, in other research that has focused on the blood–brain barrier, it has been shown that endorphin molecules are too large to pass freely, very unlikely to be the cause of the runner's high feeling of euphoria.

Other theories:

  • It has been suggested that apart from endorphins, other neurotransmitters can contribute to a runner's high; candidates include epinephrine, serotonin, and dopamine.

Hinton E, Taylor S (1986). "Does placebo response mediate runner's high?". Percept Mot Skill
^ Jump up to:a b P. B. Sparling, A. Giu¡rida, D. Piomelli, L. Rosskopf and A. Dietrich (2003). "Exercise activates the endocannabinoid system". NeuroReport 14 (15). doi:10.1097/01.
Jump up^ Raichlen, David A.; et al. (April 15, 2012). "Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’".Journal of Experimental Biology (215): 1331–1336. doi:10.1242/jeb.063677.
Jump up^ Burfoot, Amby (June 1, 2004). "Runner’s high". Runner's World.

Endorphin rush

The term "endorphin rush" has been adopted in popular speech to refer to a feeling of exhilaration that can be brought on by pain, danger, or other forms of stress, supposedly due to the influence of endorphins.
"The Reality of the "Runner's High"". UPMC Sports Medicine. University of Pittsburgh Schools of the Health Sciences. Retrieved 2008-10-15
When a nerve impulse reaches the spinal cord, endorphins that prevent nerve cells from releasing more pain signals, are released.

Endorphins are released during long, continuous workouts of moderate to high intensity, corresponding to prolonged physical stress. This also corresponds with the time that the muscles use up their stored glycogen.
The presence of endorphins would presumably mitigate pain sensation by negatively regulating pain-carrying signals from nociceptive neurons in the spinal cord. Notably, such analgesic effects of endorphins could potentially increase the likelihood of injury, as pain sensation could be more easily ignored.

A runner's high has been suggested to have evolutionary roots based on the theory that it helped with the survival of early humans.
Current African tribes make use of a runner's high when they are conducting persistence hunting. This is a method in which tribesman hunt an animal and track it for miles, eventually killing it due to its greatly increased vulnerability because it became completely physically exhausted


This result provides further evidence that the runner’s high is caused by endogenous opioid release in the brain.
What is interesting is that similar brain activation is seen for a variety of different types of rewarding events, whether they be drugs or video games or anything. This similarity of reward activation in a variety of behavioral contexts implies two things: a common system for analyzing rewards and a wide variety of things that humans have found to activate this system.
It would appear that it really is “whatever floats your boat” that you find rewarding.

”Sometimes I feel so happy sometimes I feel so sad” (Velvet Underground)

Finally, it’s useful introducing the opposite of the runner’s high, that is called hitting the wall or the bonk.
While the runner’s high occurs when muscles use up the stored glycogen, the bonk describes a condition caused by the depletion of glycogen stores, which manifests itself by sudden fatigue and loss of energy.
Milder instances can be remedied by brief rest and the ingestion of food or drinks containing carbohydrates.
The condition can usually be avoided by ensuring that glycogen levels are high when the exercise begins, maintaining glucose levels during exercise by eating or drinking carbohydrate-rich substances, or by reducing exercise intensity.

2014-01-14T12:51:07 - mirko furnari
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