Secondary Logo

Share this article on:

What Accounts for ‘Runner's High’ in Humans and Dogs?The Innate Cannabinoid Receptor System Offer Clues

Samson, Kurt

doi: 10.1097/01.NT.0000432685.78299.96
Back to Top | Article Outline


A small study showed an increase in circulating levels of two endocannabinoids in dogs and humans after intense aerobic exercise. Human subjects experienced an increase in well-being afterwards that correlated with differences between pre- and post-exercise levels of the endocannabinoids.

The “runner's high” phenomenon may be caused, at least in part, by activation of the same neurotransmitter system triggered by the primary active component in marijuana, according to a new study.

Researchers confirmed earlier data showing an increase in circulating levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) — key components of the endocannabinoid (eCB) signaling system — in a group of ten subjects after intense running sessions, but not in a matched group of subjects who walked at about half the pace.

Interestingly, similar increases occurred in dogs that were similarly tested but not in ferrets, suggesting that such physical exertion may have an evolutionary component, the researchers said. Reported in a recent issue of the Journal of Experimental Biology, it is the first study to observe differences in this phenomenon between different mammals.

Endocannabinoids are ligands — molecules or ions that help to coordinate or form more complex molecular connections — for cannabinoid receptors. They are densely expressed in neurobiological reward networks. Because they originate in the human body they are referred to as being endogenous, hence the term endocannabinoid. The primary psychoactive ingredient in marijuana, delta-9-tetrahydrocannabinol (THC), activates the same neurobiological pathways in the brain.

In the study led by David A. Raichlen, PhD, associate professor in the School of Anthropology at the University of Arizona in Tucson, ten healthy individuals engaged in 30 minutes of high-intensity treadmill running at an average of 72 percent of maximal heart rate, while another eight walked 44 percent of maximal heart rate. AEA and 2-AG levels were tested in blood samples collected before and after exercise sessions, as was a standard psychological well-being assessment.

All of the endurance runners experienced an increase in well-being afterwards that correlated with differences between pre- and post-exercise levels of AEA.

The study was limited by the small number of runners involved and the fact that eCBs were only measured in the bloodstream, Dr. Raichlen told Neurology Today in a telephone interview; however, the robust correlation between eCB changes and positive affect indicate similar increases in the central nervous system, and the fact that eCBs easily cross the blood–brain barrier,

In addition to increased well-being, higher eCBs levels also appear to have an analgesic effect in trained runners, helping them with endurance, Dr. Raichlen said.

Back to Top | Article Outline


Although levels of the two ligands rose in runners, the researchers did not test for a specific mechanical trigger of eCB signaling. However there appears to be a threshold intensity level for eCB signaling and the resultant rewards, he noted.

In the current study, participants exercised at 70 percent aerobic capacity, while another study found similar increases in levels of AEA and 2-AG and positive affect at up to 80 percent capacity. Signaling is not triggered at intensities above or below those levels, said Dr. Raichlen.

“What we seem to have is this unique sweet spot for achieving eCB signaling.”

For years, the runner's high phenomenon has been attributed to the release of endorphins, but the role of eCBs has come under increased scrutiny as also contributing to the effect.

“Endorphins and eCBs work together in high-intensity exercise, but unlike endorphins, eCBs can be produced peripherally. Nonetheless, both pathways are being triggered at this level of exercise.”

“This line of research is still in its infancy,” he noted, adding that eCB signaling needs to be studied in larger groups with a more varied athletic history, and in individuals who do not seem to experience significant eCB signaling regardless of exercise intensity.

“We call this the ‘push-pull’ effect, and believe that training might be involved. Couch potatoes cannot seem to reach this sweet spot, so it may take some gradual aerobic training before they can start getting the eCB effect.”

Another explanation may be that eCB receptor density varies among individuals, he said, or that inactive individuals may react differently to eCBs while others may not like the effect.

“One thing we do not see is people who feel worse after endurance exercise, but this variation in psychological improvement is another area that needs more investigation.”

Back to Top | Article Outline


In 2003, researchers at the Georgia Institute of Technology in Atlanta first reported that even moderate exercise activated AEA, but not 2-AG, with similar mood elevation, and that eCB activation appeared to be intensity-dependent.

The link between endorphins and intense exercise has been more clearly established. In 2008, German researchers put the endorphin hypothesis to the test, using positron emission tomography (PET) to track the activity of a radioactive endorphin competitor in individuals after a two-hour distance run. They discovered that opioid receptors in the brain became increasingly blocked as more endorphins were released, and that these were predominantly in the prefrontal and limbic brain regions that play a key role in emotional processing. Moreover, they observed a significant increase in euphoria and happiness ratings after running.

This led them to posit that endorphins facilitate the body's own pain suppression, acting as a painkiller, by influencing the way the body processes pain in the nervous system and brain.

Back to Top | Article Outline


Raphael Mechoulam, PhD, professor of chemistry at Hebrew University of Jerusalem in Ein Kerem, Israel, said that he is “somewhat skeptical” about the findings, which he said were “relatively limited.”

In 1964, Dr. Mechoulam and his colleague, Dr. Yechiel Gaoni, were the first to identify and synthesize THC. In 1992, he and his colleagues identified AEA as the brain's first endogenous cannabinoid, and later 2-AG.

He told Neurology Today that while the authors confirmed earlier observations on the role of AEA and 2-AG in strenuous exercise, other explanations are possible. For example, he cited two recent studies by researchers in Europe, led by Elsa Heyman, PhD, at the University Lille Nord de France, that implicated brain-derived neurotrophic factor (BDNF) in the reward mechanism of intense exercise.

“They should have taken the opportunity to look at changes in the levels of other relevant endogenous molecules,” he said.

The novel aspects are the observations on dogs, Dr. Mechoulam said, which parallel observations in humans, and the lack of effect on ferrets, and that dogs may not have any specific affective response under these experimental conditions.

“This is an unexpected observation because dogs certainly require some walking every day — otherwise they are quite unhappy. I wonder whether their BDNF goes up.”

Back to Top | Article Outline


•. Raichlen DA, Foster AD, Gerdman GL, et al. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner's high.’ J Exp Biol 2013;215:1331–1336.
    •. Boecker H, Sprenger T, Spilker ME, et al. The runner's high: Opioidergic mechanisms in the human brain. Cereb Cortex 2008;11:2523–2531.
      •. Raichlen DA, Foster AD, Seillier A, et al. Exercise-induced endocannabinoid signaling is modulatedby intensity. Eur J Appl Physiol 2013;113:869–875.
        •. Straiker A, Mackie K. Cannabinoid signaling in inhibitory autaptic hippocampal neurons. Neurosci 2009:163:190–201.
          •. Sparling PB, Giuffrida A, Piomelli D, et al. Exercise activates the endocannabinoid system. Neuroreport 2003;14:2209–2211.
            •. Heyman E, Gamelin FX, Goekint M, et al. Intense exercise increases circulating endocannabinoid and BDNF levels in humans — Possible implications for reward and depression. Psychoneuroendocrinology 2012; 37:844–85.
              •. Heyman E, Gamelin FX, Acouturier J, Di Marzo V., et al. The role of the endocannabinoid system in skeletal muscle and metabolic adaptations to exercise: potential implications for the treatment of obesity. Obes Rev 2012;13:1110–1124.
                © 2013 American Academy of Neurology