Cannabis Receptors and the Runner’s High

[First published August 4 2010]

Maybe it isn't endorphins after all.

What do long-distance running and marijuana smoking have in common? Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined.

The nature of the runner’s high is inconsistent and ephemeral, involving several key neurotransmitters and hormones, and therefore difficult to measure. Much of the evidence comes in the form of animal models. Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

A Canadian neuroscientist who blogs as NeuroKuz suggests that “a reduction in CB1 levels could lead to less binding of endocannabinoids to receptors in brain circuits that drive motivation to exercise.” NeuroKuz speculates on why this might be the case. Physical activity and obtaining rewards are clearly linked. The fittest and fleetest obtain the most food. “A possible explanation for the runner’s high, or ‘second wind,’ a feeling of intense euphoria associated with going on a long run, is that our brains are stuck thinking that lots of exercise should be accompanied by a reward.”

In 2004, the British Journal of Sports Medicine ran a research review, “Endocannabinoids and exercise,” which seriously disputed the “endorphin hypothesis” assumed to be behind the runner’s high. To begin with, other studies have shown that exercise activates the endocannabinoid system.

“In recent years,” according to the authors, “several prominent endorphin researchers—for example, Dr Huda Akil and Dr. Solomon Snyder—have publicly criticised the hypothesis as being ‘overly simplistic,’ being ‘poorly supported by scientific evidence’, and a ‘myth perpetrated by pop culture.’” The primary problem is that the opioid system is responsible for respiratory depression, pinpoint pupils, and other effects distinctly unhelpful to runners.

The investigators wired up college students and put them to work in the gym, and found that “exercise of moderate intensity dramatically increased concentrations of anandamide in blood plasma.” The researchers break the runner’s high into four major components. Exercise, they say, “suppresses pain, induces sedation, reduces stress, and elevates mood.” Some of the parallels with the cannabis high are not hard to tease out: “Analgesia, sedation (post-exercise calm or glow), a reduction in anxiety, euphoria, and difficulties in estimating the passage of time.”

There are cannabinoid receptors in muscles, skin and the lungs. Intriguingly, the authors suggest that unlike “other rhythmic endurance activities such as swimming, running is a weight bearing sport in which the feet must absorb the ‘pounding of the pavement.’” Swimming, the authors speculate, “may not stimulate endocannabinoid release to as great an extent as running.” Moreover, “cannabinoids produce neither the respiratory depression, meiosis, or strong inhibition of gastrointestinal motility associated with opiates and opioids. This is because there are few CB1 receptors in the brainstem and, apparently, the large intestine.”

A big question remains: What about running and the “motor inhibition” characteristic of high-dose cannabis? (An inhibition that may make cannabis useful in the treatment of movement disorders like tremors or tics.) Running a marathon is not the first thing on the minds of most people after getting high on marijuana.  The paper maintains, however, that at low doses, “cannabinoids tend to produce hyperactivity,” at least in animal models. The CB1 knockout mice were abnormally inactive, due to the effect of cannabinoids on the basal ganglia. Practiced, automatic motor skills like running are controlled in part by the basal ganglia. The authors predict that “low level skills such as running, which are controlled to a higher degree by the basal ganglia than high level skills, such as basketball, hockey, or tennis, may more readily activate the endocannabinoid system.”

The authors offer other intriguing bits of evidence. Anandamide, one of the brain’s own cannabinoids, “acts as a vasodilator and products hypotension, and may thus facilitate blood flow during exercise.” In addition, “endocannabinoids and exogenous cannabinoids act as bronchodilators” and could conceivably facilitate breathing during steady exercise. The authors conclude: “Compared with the opioid analgesics, the analgesia produced by the endocannabinoid system is more consistent with exercise induced analgesia.”

Photo Credit: http://www.madetorun.com/

Treadmill Rehab

The curious connection between exercise and getting high.

A Vanderbilt study published in the journal PLoS ONE has confirmed what readers of Addiction Inbox have known for some time: Exercise often helps to curb cravings for addictive drugs. The Vanderbilt paper is noteworthy for focusing on heavy marijuana smokers (6 joints per day) who had not expressed any interest in quitting. Yet, at the end of a modest two-week exercise regimen, the participants reported less cannabis use.

Last August, I wrote about a growing body of research suggesting that the runner’s high and the cannabis high were more similar than previously imagined. Investigators wired up college students, put them to work in a gym, and found that “exercise of moderate intensity dramatically increased concentrations of anandamide in blood plasma.”

The British Journal of Sports Medicine ran a research review, “Endocannabinoids and exercise,” which seriously disputed the “endorphin hypothesis” assumed to be behind the runner’s high. The primary problem is that the opioid system is responsible for respiratory depression, pinpoint pupils, and other effects distinctly unhelpful to runners and other strenuous exercisers.

Compared to endorphins, the analgesia produced by the endocannabinoid system is much more consistent with the demands of exercise. Very high doses of marijuana tend to have a sedating effect, but low doses tend to induce activity or hyperactivity. There are cannabinoid receptors in muscles, skin, and the lungs. Moreover, “cannabinoids produce neither the respiratory depression, meiosis, or strong inhibition of gastrointestinal motility associated with opiates and opioids,” according to the research review. "This is because there are few CB1 receptors in the brainstem and, apparently, the large intestine.”

In addition, in my 2008 post entitled “Battling Addiction with Exercise,” I highlighted director Nora Volkow’s remarks at a NIDA-sponsored conference on addiction treatment and research. "Exercise has been shown to be beneficial in so many areas of physical and mental health," Volkow said. "This cross-disciplinary meeting is designed to get scientists thinking creatively about its potential role in substance abuse prevention."

At the same conference, Dr. Bess Marcus of Brown University, working on a NIDA-funded study of exercise for smoking cessation, presented the scientific evidence for the addiction/exercise connection. Similarities in the effects on the reward pathways of the brain's limbic system--dopamine activity in particular--may tie the two behaviors together more directly than previously thought. Among the findings:

--Rats in cages with running wheels show less interest in amphetamine infusions than rats without exercise options.

--Baby monkeys who don't roughhouse with their peers have higher levels of impulse control problems and alcohol use when they get older.

--In humans, exercise is known to reduce stress and tension--and anxiety is a well-known side effect of withdrawal, from alcohol and cigarettes to heroin and speed.

--Physical activity may enhance cellular growth in key areas of the brain involved in addiction, thereby aiding the neural changes that take place during detoxification and withdrawal from addictive drugs.

Photo Credit: http://www.livestrong.com/