Your brain on exercise: rewarded with dopamine by cannabinoid receptors.

Lack of enough physical activity is a huge problem in the obesity-plagued modern world. With much of physical activity removed from work and daily life, to be fit and not obese, we have to exercise for extended periods of time, in activities like jogging, fast walking, bike riding and other aerobic exercise. Our willingness to exercise in this way is really a cornerstone of our health, and our society’s health. Probably more than anything single factor, our health care system would benefit from people getting more exercise. New research now reports the crucial role of cannabinoid receptors and our endocannabinoid regulatory system in our motivation to keep moving.

Research out of France, reported in Biological Psychiatry shows how small protein cannabinoid receptors operating in the walls of nerve cells in the  brain reward exercise. This unlocks a key to voluntary exercise, and perhaps ways to promote it.  Also reported in ScienceDaily, the research reported that the endocannabinoid system, especially CB1 receptors in certain parts of the brain, reward our bodies and minds with pleasurable sensations. This research was with mice, not humans, but the physiology and responses are very similar. Lack (or blockage) of these receptors caused a sharp drop in the amount of exercise control mice were willing to do.

For us to continue to exercise, rather than stopping, depends a lot on how we feel. If tired and uncomfortable we might well stop; if exhilarated and “in the zone,” we continue. How we feel during exercise, it turns out, depends much on how much of the feel-good substance, dopamine, our brains produce and receive.  Our dopamine levels, this research shows, are controlled in part by our endocannabinoid systems and CB1 receptors in certain parts of the brain. CB1 receptors are activated by our natural endocannabinoids such as anandamide. They also fit like lock and key and are activated by plant cannabinoids, especially THC, from cannabis.

Dopamine is an organic chemical produced in several areas of the brain. Many brain functions involve dopamine, especially learning, voluntary movement, reward and motivation. We feel higher dopamine levels as enjoyment and are rewarded by the experience, making us want to continue or repeat. Drugs like cocaine increase and prolong dopamine levels. The Bordeaux, France researchers studied dopamine producing nerve cells in the brain’s ventral tegmental area (VTA) known to play an important role in motivation. By working with mice with CB1 receptors present or absent or blocked, they found marked difference in how much running wheel time the rodents would spend.

The researchers had previously found “that the endogenous stimulation of cannabinoid type-1 (CB1) receptors is a prerequisite for voluntary running in mice,” but did not understand the mechanisms. In experiments involving “in vivo electrophysiology, the consequences of wheel running on VTA dopamine (DA) neuronal activity” on mice with combinations of CB1 blockage and GABA blockage. GABA is an inhibitory neurotransmitter that reduces levels of dopamine produced by other neurons. Cannabinoid receptor activation in GABA neurons inhibits this inhibitory effect on dopamine. This “inhibition of inhibition” results in an increased level of dopamine produced in this motivation area of the brain.

Exercise promotes endocannabinoid activation of CB1 receptors and this activation encourages continued exercise. If we exercise enough to allow them, our bodies reward us for the physical activities that are so good for us.

Not mentioned in this research, the “runner’s high” is likely a function of endocannabinoids, along with the endorphins. For earlier evidence of the runner’s high association with the endocannabinoid system check Runner’s high – your body rewarding exercise.

Runner’s high – your body rewarding exercise.

Runners have long noted that euphoria and sense of well-being are often felt during and after a hard run. Indeed, this mental and physical reward is the reason many runners exercise. The ability to run quickly and for long distance is obviously an important evolutionary advantage, as in the capability  to catch food or not.

The “high” experienced by runners and others exercising vigorously has long been explained by endorphins and the opioid receptor system. But since this explanation came the discovery of the endocannabinoid (eCB) regulatory system consisting of receptors on nerve and other cells and natural cannabinoids (CBs) that activate these receptors,. For nearly a decade many have thought that this system better explains the mental lift and euphoria people often feel during and after robust exercise.

Now a study in the Journal of Experimental Biology, “Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high“,  expands on the evolutionary importance of this pleasurable signalling.  The term “cursorial” means well adapted to running. Human being and dogs are cursorial, ferrets, not so much. In this research, intense exercise dramatically raised the levels of endocannabinoids in humans and dogs, in ferrets, not so much. The researchers concluded, “Thus, a neurobiological reward for endurance exercise may explain why humans and other cursorial mammals habitually engage in aerobic exercise despite the higher associated energy costs and injury risks, and why non-cursorial mammals avoid such locomotor behaviors.

This “neurobiological reward” occurs when your body’s own eCB, anandamide, activates cannabinoid receptors CB1 on nerve cells in brain and body.  Anandamide (AEA) and similar 2-AG, activate these nerve receptors in much the same way as does the plant cannabinoid THC, from the plant cannabis sativa. Activation of CB1 receptors by any of these cannabinoids provides a euphoric effect. As the release of anandamide is stimulated by intensive exercise such as running, your body provides a rewarding euphoria for a hard run or workout.

Regrettably perhaps, achieving this runner’s high requires fairly robust levels of exercise. Seemingly we must “pay for” the experience with quite hard physical labor; walking did not increase CB levels in this study. But don’t let that discourage you from walking; it offers dozens of other rewards, even health itself.

Running speed and prevention of cardiovascular disease.

Running speed a great indicator of health.

Running speed a great indicator of health.

The key role of cardiovascular exercise in keeping healthy and hearty has been confirmed in a couple of important studies. They point out the amount of time it takes you to run a mile is a great indicator of cardiovascular health and your danger of heart attack and stroke.

Reported in Red Orbit and elsewhere, two studies of this behavioral indicator of cardiovascular health, showed that for middle-aged men, the length of time required to run one mile (1,609 meters) predicted heart attack and stroke better than did blood pressure or cholesterol levels.

Faster times predict fewer heart and brain attacks. A 55 year old male who requires 15 minutes to walk/run a mile (only 4 miles per hour) faces a 30% chance of suffering cardiovascular disease. A man of the same age who can run a mile in just 8 minutes (7.5 miles per hour) faces far lower danger of cardiovascular disease, less than 10 percent.

One way to increase running speed is with interval training, brief bursts at higher speed. After warm up jogging, a common interval is one minute slow jogging speed followed by one minute high intensity running, then repeating the sequence up to 10 times. This writer has been experimenting with slow jog/fast walk for 90 seconds, interspersed with 30 seconds high speed. This rhythm seems well suited for a non-punishing work-out made plenty intense with the periods at high speed. These high speed intervals quickly boost heart rate and sweating, both goals of a good conditioning, fat-burning workout.

High levels of physical activity such as running seem to correspond with activation of the endocannabinoid regulatory system, the receptor based system also activated by the THC in cannabis. Indeed, the fabled “runner’s high” might be the result of this system, rather than (or in addition to) to endorphins. More about this in a future post.

Caution: For those poorly conditioned, increasing activity and especially trying to push up maximum speed can present some dangers. A consultation with your (fit) medical practitioner and taking a stress EKG test is a good precaution.

Caution: Being poorly conditioned and not participating in physical activity presents an enormous risk of cardiovascular disease, along with obesity, diabetes and a host of other diseases.

Bliss out (and pump up) your brain with exercise.

Just as doing push-ups pumps up the size of your triceps, so does aerobic exercise appear to increase the volume of your brain! American researchers reporting in the British Journal of Sports Medicine show that physical exercise, especially aerobic activity, improves the functioning and structure of the brains of older people.

Improvements in brain size, with increased volumes of grey and white matter, and better brain function were found in both those with and without dementia. The so called functions of “executive control,” that help us carry on our lives planning, remembering and changing tasks are those first attacked by dementia. But study co-author Art Kramer of the University of Illinois notes that these functions are those most helped with exercise. Dementia is not only forestalled, but in some ways actually reversed with 6 months of aerobic activity. Brains benefiting from the exercise exertions of their owners maintained plasticity, essentially the capabilities to continue growing, developing and learning.

Although huge rewards accrue to both brain and body from simply walking, these researchers point out the increased benefit from more rigorous aerobic activities, such as jogging, that cause increases in heart rate and rate of breathing. So by all means walk your 10,000 steps a day, at least 5 miles, but also pick up the pace for some of those steps.  Jogging one of those five miles and moving your heart rate up into your age-appropriate training zone will yield great benefits, toning your body and growing your brain. Professor Kramer summarized, “We can safely argue that an active lifestyle with moderate amounts of aerobic activity will likely improve cognitive and brain function, and reverse the neural decay frequently observed in older adults.”

If you bliss out your brain with exercise, there is now good evidence your brain will return the favor. “Runner’s high,” is a flowing, blissful, pain-free experience associated with aerobic exercise. Formerly, the enjoyable mental and physical state was associated solely with endorphins, the body’s natural opiates. With the discovery of the endocannabinoid receptor system and endogenous cannabinoids produced by our own bodies, such as anandamide and 2-AG, this explanation is taking a new turn. After you begin exercising, your level of natural bliss cannabinoid anandamide elevates, and more of these bliss molecules float in your bloodstream, ready to jump the blood-brain barrier and activate CB1receptors on your nerve cells. The result is pain reduction and mood elevation.  So, in addition to endorphins, endocannabinoids such as anandamide reward you for your exercise efforts.

Better adaptive functioning and increased brain volumes are, at least in part, due to neurogenesis, the birth of new brain cells. Both exercise and cannabinoids promote neurogenesis. So, to gain huge health rewards, second-by-second, year-by-year, for your entire life, bliss out your brain with exercise. Walk every day, run some too, lift some weights, and every cell in your brain and body benefits.