Have you ever felt a sense of relaxation, happiness, and even a certain euphoria after engaging in physical activity?

This feeling has a name: runner's high. It is a fleeting experience that some people undergo during and after endurance exercises, characterized by reduced pain sensitivity, sedation, euphoria, and decreased anxiety. Some also report a loss of time perception and a sense of effortlessness. Recent evidence in mice suggests that this euphoria is related to the release of endocannabinoids (eCBs) during exercise.
 

Historically, studies from the 1980s attributed runner's high to the release of endorphins — hydrophilic molecules that bind to opioid receptors. However, this hypothesis lacks robust evidence. For example, due to being hydrophilic, endorphins cannot penetrate the blood-brain barrier and therefore have little effect on the brain. Additionally, no consistent correlation has been found between peripheral levels of endorphins during endurance exercises and mood elevation.

Studies have also shown that blocking the opioid system does not alter the subjective experience of exercise. In the 1990s, the two main endogenous endocannabinoids (eCBs) were discovered: anandamide (AEA), also known as arachidonoylethanolamide, in 1992, and 2-arachidonoylglycerol (2-AG) in 1995. Unlike endorphins, eCBs are lipophilic, being able to easily cross the blood-brain barrier, making them more likely candidates to explain runner's high.

The endocannabinoid system is a potent endogenous system involved in various physiological functions in the nervous system, including synaptic transmission, mood, reward, anxiety, appetite, memory processing, neuroprotection, and neuroinflammation. It also plays important roles in neural development, such as proliferation, neuronal migration, and axonal growth. The two main eCBs, AEA and 2-AG, bind to G protein-coupled cannabinoid receptors, CB1 and CB2.

Studies in animal models have shown that two criteria of runner's high — hypoalgesia and anxiolysis — are indeed related to increased eCB levels after exercise.

Acute exercise and AEA levels

The increase in AEA is a consistent finding after a workout session. In a review of 17 studies, 14 (82%) detected an increase in AEA after acute exercises. Four samples found no difference (15%) and one observed a decrease (4%). Most studies used moderate-intensity exercises, between 70% and 85% of the maximum heart rate adjusted for age (HRmax), compared to less intense conditions such as walking or sitting. All studies with a control group described an increase in AEA compared to the control condition.

In 2012, a study with 11 young, well-trained male cyclists used a standardized protocol, without exercise, alcohol, or coffee in the previous 24 hours, and provided a uniform breakfast. The participants cycled for 60 minutes at 55% of maximum power output (W max.), followed by 30 minutes at 75% of W max. AEA levels increased after intense exercise and continued to rise during recovery, while 2-AG levels remained stable. Other eCB-like lipids, such as PEA and OEA, also gradually increased. However, 60 minutes of cycling at 55% of W max. did not significantly increase AEA levels.

Tomorrow is Monday, World Changing Life Day. How about starting a physical activity and helping your body regulate the endocannabinoid system, producing more 'happiness molecules'? Shall we?