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Runner's high, the calm, euphoric feeling some people get during or after long exercise, was long credited mainly to endorphins. Experiments in mice and studies in people now suggest that endocannabinoids, signalling molecules the body makes that act on the same receptors as cannabis, play an important part in easing anxiety and pain after exercise.

Fuss et al., PNAS (2015) and subsequent research

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Endorphins are the body's own opioids, chemicals that act like morphine. A 2008 brain-scan study in runners found opioid activity rising after a two-hour run, which supported the old explanation. But endorphins in the blood barely reach the brain, and in 2015 a German team showed that blocking cannabinoid receptors in mice took away the calming and pain-relieving effects of running, while blocking opioid receptors did not. A 2021 study in people found a similar pattern: runners still felt the high when their opioid receptors were blocked, and their endocannabinoid levels rose. Many researchers now think endocannabinoids do much of the work, though opioids may also play a part.

Türkçe oku
Koşucu sarhoşluğu, uzun süre egzersiz yapan bazı insanların yaşadığı dingin ve coşkulu hâldir; bu his uzun zaman başlıca endorfinlere bağlandı. Fare deneyleri ve insanlarla yapılan çalışmalar ise vücudun ürettiği ve esrarla aynı reseptörlere etki eden endokannabinoid adlı sinyal moleküllerinin, egzersizden sonra kaygının ve ağrının azalmasında önemli rol oynadığını gösteriyor.

Endorfinler vücudun kendi ürettiği opioidlerdir, yani morfin gibi etki eden kimyasallardır. 2008'de koşucularla yapılan bir beyin görüntüleme çalışması, iki saatlik bir koşudan sonra beyinde opioid etkinliğinin arttığını gösterdi ve eski açıklamayı destekledi. Ama kandaki endorfin beyne neredeyse hiç geçemez. 2015'te bir Alman ekibi, farelerde kannabinoid reseptörleri engellendiğinde koşunun sakinleştirici ve ağrı kesici etkisinin kaybolduğunu, opioid reseptörleri engellendiğinde ise kaybolmadığını gösterdi. 2021'de insanlarla yapılan bir çalışma da benzer bir tablo buldu: opioid reseptörleri engellenen koşucular bu coşkuyu yine yaşadı ve kanlarındaki endokannabinoid düzeyi yükseldi. Bugün pek çok araştırmacı işin büyük kısmını endokannabinoidlerin yaptığını, opioidlerin de payı olabileceğini düşünüyor.

Sources and further reading

Background reading: Runner's high
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Deliberately smiling can make people feel slightly happier. In 2022 a study of nearly 4,000 people in 19 countries found that posing a smile, or copying a smiling face, raised reported happiness a little; a subtler method, holding a pen between the teeth, gave less clear results.

The idea that the face can feed back into feelings, called the facial feedback hypothesis, goes back to Charles Darwin and William James. In a famous 1988 experiment, Fritz Strack and colleagues had people hold a pen in their teeth, which forces a smile, or between their lips, which prevents one, and those in the first group rated cartoons as funnier. In 2016, seventeen laboratories repeated that experiment exactly and found no effect. A 2019 review of 138 studies concluded that the effect is real but small and varies from study to study. The 2022 Many Smiles Collaboration, led by Nicholas Coles and designed jointly by supporters and sceptics of the idea, found that deliberate smiling could both strengthen and start feelings of happiness, while the pen method remained inconclusive.

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A 2016 estimate found that a typical adult man weighing 70 kg has about 30 trillion human cells and 38 trillion bacteria. That overturned the old claim that bacteria outnumber our own cells ten to one: the two numbers are roughly equal.

The estimate comes from Ron Sender, Shai Fuchs and Ron Milo of the Weizmann Institute of Science in Israel. Their reference man is 20 to 30 years old, 170 cm tall and weighs 70 kg. The ten-to-one figure, they found, went back to a single rough calculation from 1972 that had been repeated for decades. Almost all the bacteria live in the colon, the last part of the gut, and together they weigh only about 0.2 kg. Among human cells, red blood cells dominate the count, making up about 84 per cent, while fat and muscle cells, far fewer but much larger, make up most of the body's cell mass. The balance also shifts through the day: a single trip to the toilet empties a quarter to a third of the colon's contents.

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An adult body replaces about 330 billion cells every day, around 80 grams of cells, according to a 2021 estimate by scientists at the Weizmann Institute of Science. Close to nine in ten of those cells are blood cells.

Ron Sender and Ron Milo combined the number, mass and lifespan of every major cell type in the body. Short-lived cells dominate the count. Red blood cells live about four months, and neutrophils, the most common white blood cells, only days, so the bone marrow must make vast numbers of them every day. By mass, the largest shares come from blood cells and from the cells lining the gut, which are shed and replaced within days. At this pace, a number of cells equal to all the roughly 30 trillion human cells in the body is replaced in about three months. That does not mean the whole body is renewed: most nerve cells in the brain last a lifetime, and heart muscle cells are replaced only very slowly.

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Your gut and brain communicate through nerves, hormones, immune signals and microbes, which is why stress and digestion can affect each other.

Scientists call this link the gut–brain axis. The gut has its own network of about 500 million nerve cells, the enteric nervous system, sometimes called the “second brain”, which can run digestion largely by itself. It is connected to the brain mainly through the vagus nerve, a long nerve running from the brainstem down to the abdomen, and most of its fibres carry messages upwards, from the gut to the brain. More than 90 per cent of the body's serotonin, a chemical messenger, is found in the gut. Gut bacteria play a part too: in a 2004 Japanese study, mice raised entirely free of germs overreacted to stress. Stress can speed up or slow down the gut, one reason it often worsens irritable bowel syndrome, a common gut disorder. Most research on the microbes' role has been in animals, and human evidence is still limited.

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A placebo is a dummy treatment, such as a sugar pill. In pain studies, placebos can reduce the pain people report and also dampen activity in the brain areas that process pain, even though they contain no active drug.

The word placebo is Latin for “I shall please”. One of the first clues that the effect is physical came in 1978, when Jon Levine and colleagues studied patients recovering from wisdom tooth removal. They gave them a placebo and naloxone, a drug that blocks the effect of endorphins, the body's own painkilling chemicals. In patients who had responded to the placebo, naloxone increased the pain, which suggested that the placebo relief came from endorphins. In 2004 Tor Wager and colleagues used brain scans to show that a placebo painkiller reduced activity in pain-processing regions during a painful stimulus. Expectation works the other way too: in the nocebo effect, from the Latin for “I shall harm”, expecting harm makes symptoms worse. None of this means the pain was imaginary, or that placebos can replace effective treatment.

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