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Understanding Runner's High
Runner's high, a physical and psychological phenomenon that manifests for many during endurance exercise, has for years been attributed to the endogenous opioid endorphin. Turns out that's completely wrong. Read on for the true science of this common—and, until now, misunderstood—experience of those who engage in intense and prolonged exercise.
The phenomenon of "runner's high" has been touted in the popular press for decades. The sometimes bliss-like euphoria experienced by people engaging in endurance exercise has, since the 1980s, been attributed to endorphin. This is the pain-killing hormone produced in the central nervous system, by the pituitary gland, that is, technically, an endogenous opioid.
"Endorphin can't cross the blood-brain barrier to bind with CB1 receptors."
Endorphin, however, can't cross the blood-brain barrier to bind with CB1 receptors in the brain (part of the body's endocannabinoid system, or ECS) to create euphoria. This is for several reasons, one of which is that the endorphin molecule is simply physically too large to permeate this critical barrier.
It turns out that the endocannabinoid anandamide—not endorphin—is the mystery molecule responsible for runner’s high (it binds with CB1 receptors). Like its mimetic molecular cousin tetrahydrocannabinol, or THC, anandamide causes the euphoria, joy, and sometimes pronounced mood shift associated with the runner's high mechanism that is experienced by many during intense endurance exercise.
2021 Study: Runner's High Study
Understanding Runner's High. A 2021 study entitled "Exercise-induced Euphoria and Anxiolysis Do Not Depend on Endogenous Opioids in Humans" that was published in the journal Psychoneuroendocrinology explored the phenomenon of exercise euphoria commonly called runner's high that has traditionally been attributed to the endogenous (internally produced) pain killer endorphin.
Defining Runner's High
The study described the runner's high phenomenon as "a sense of well-being during endurance exercise characterized by euphoria and anxiolysis [anxiety reduction]. It has been a widespread belief that the release of endogenous opioids, such as endorphin, underlie a runner's high."
However, the study noted that exercise leads to the release of two classes of "rewarding molecules," endocannabinoids (such as 2-AG and anandamide) and opioids (such as endorphin).
The study noted that exercise leads to the release of two classes of "rewarding molecules," endocannabinoids (such as 2-AG and anandamide) and opioids (such as endorphin).
In preclinical studies involving rodents, "we have shown that core features of a runner's high depend on cannabinoid receptors, not opioid receptors." The researchers behind this study had the goal of revealing the source and underlying mechanism of runner's high with human study subjects.
Exercise Produces Endocannabinoids
The study gathered data on 63 participants who "exhibited increased euphoria and decreased anxiety after 45 minutes of running on a treadmill in a moderate-intensity range." The study's authors described how running resulted in higher levels of the endocannabinoids 2-AG and anandamide.
It should be noted that the popular commercial cannabinoids cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC) are considered mimetic molecules because they produce similar efficacy to their endocannabinoid chemical cousins 2-AG and ananadamide. Generally speaking, CBD mimics 2-AG and THC imitates anandamide.
The study revealed that this opioid blockage did not prevent the development of euphoria, including "elevation of endocannabinoid levels following exercise."
To test the effect of the endocannabinoids on euphoria and anxiety levels, opioid blockers were employed. The study revealed that this opioid blockers did not prevent the development of euphoria and reduced anxiety in study participants, nor did it prevent "elevation of endocannabinoid levels following exercise."
Runner's High Study Conclusions
This study indicates that the development of a runner's high does not depend on opioid signaling in humans, but instead results from the production of endocannabinoids such as 2-AG and anandamide. While this dynamic had been revealed previously in rodent models, this study was the first to validate endocannabinoids as the source of runner's high via a controlled study of humans.
View the original study.
Anandamide Research
Understanding Runner's High. Interestingly, anandamide is produced outside of the human body by multiple plants, including truffles (the winter black variety) and cacao.
2019 Anandamide Study
A 2019 study explored the ability of anandamide to reduce anxiety. "Our data suggest that...elevated [anandamide]...reduces stress, anxiety, and fear." The research uncovered "new insights on the mechanisms by which...endocannabinoid signaling regulates emotional behavior."
"Our data suggest that...elevated [anandamide]...reduces stress, anxiety, and fear."
The study found a direct relationship between anandamide levels and emotional behavior and identified the areas of the brain in which this mechanism occurs. "Our results indicate that the ability of anandamide signaling to regulate emotional behavior is nonlinear and may involve actions at distinct neuronal populations, which could be influenced by the basal level of anandamide."
2015 Anandamide Study
According to a 2015 study, "truffles contain the major metabolic enzymes of the ECS, [but] do not express the most relevant endocannabinoid-binding receptors [CB1 and CB2]."
The levels of anandamide produced by cacao and found in dark chocolate are believed to be too low to affect a consumer's psychological state via an improvement of mood. Reported the 2015 book Chocolate and Health: Chemistry, Nutrition, and Therapy, "It is unlikely that chocolate’s anandamide level could actively trigger a psychological response."
"The levels of anandamide produced by cacao and found in dark chocolate are believed to be too low to affect a consumer's psychological state via an improvement of mood."
However, cacao produces two chemicals that are similar to anandamide that synergistically interact with the ECS to prevent the metabolic breakdown of anandamide. This results in increased bioavailability and greater potency than would be achieved by anandamide acting in isolation. The potency amplification and mood improvement resulting from the synergistic interplay of these three molecules manufactured by cacao may result in true mood improvement—and help explain the craving that some humans experience for dark chocolate.
2015 Anandamide Study
A 2015 study investigated the ability of anandamide to diminish or erase fear-based memories, making it of potential therapeutic value in the treatment of trauma-related conditions such as Post-traumatic Stress Disorder and social anxiety. "Our results demonstrated enhanced fear extinction in human and mouse carriers," reported the study, including "reduced levels of...anxiety."
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