The “runner's high” is a rare case of a folk explanation that survived half a century and turned out to be wrong. Ask anyone on a start line where that state comes from and you will hear about endorphins. Meanwhile the data of the past ten years point to a different system — the endocannabinoid one, the very system cannabis acts on. In September 2026 BMC Medicine published a study that for the first time followed this biochemistry across a whole race distance rather than in a 45-minute laboratory run.

Why endorphins do not work as an explanation

Endorphins are large peptides. The problem with the classic hypothesis is that they barely cross the blood–brain barrier: what is measured in the blood never reaches the brain. Direct evidence about the brain did exist: Boecker and colleagues (Cerebral Cortex, 2008) used PET to show that after a two-hour run the binding of opioid ligands in the brain changes, and the more so the greater the euphoria reported.

The decisive experiment came later. Fuss and colleagues (PNAS, 2015) showed in mice that the key features of the runner's high — reduced anxiety and analgesia — disappear when cannabinoid receptors are blocked and survive when opioid receptors are. Then it was tested in humans: Siebers and colleagues (Psychoneuroendocrinology, 2021) gave 63 participants naltrexone — an opioid receptor blocker — or placebo and sent them off for 45 minutes of running or walking. Blocking opioids did not prevent the euphoria, the drop in anxiety or the rise in plasma endocannabinoids. The proportion of people who subjectively reported a “high” was the same in both groups.

One gap remained: the whole picture was built on efforts shorter than an hour. And people run for hours and for days.

What was done at the marathon and the ultra

The group led by Siebers and Fuss ran two field studies.

Study 1. 19 trained runners ran a marathon and, on a separate day, walked for the same length of time. Blood was drawn every 14 km during the race and once more after 45 minutes of rest. They measured anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid and palmitoylethanolamide by liquid chromatography–mass spectrometry. Alongside this, visual analogue scales of euphoria, anxiety and pain.

Study 2. 36 ultramarathoners racing 100, 160 and 230 km gave blood before and after the race.

What came out

Anandamide rose all the way. During the marathon AEA climbed progressively from one sampling point to the next and was still elevated 45 minutes after the finish. Walking for the same length of time produced only moderate shifts. After the ultramarathons, at all three distances, AEA was also above baseline.

2-AG behaved differently. In the marathon it rose only in the late stages of the run and in early recovery. In the ultrarunners a rise in 2-AG was recorded after the race at every distance — that is, a delayed response tied to recovery rather than a reaction to the work itself.

The sensations matched the biochemistry only in part. Compared with walking, the marathon produced more euphoria and less anxiety; pain started to rise after the 28th kilometre. After the ultramarathon the picture was different: pain rose, anxiety fell — and euphoria did not change significantly.

That last point is the most interesting thing in the study. The molecules considered the substrate of the “high” are elevated after 230 km, and the high itself is absent.

How to read this

This is an association, not a mechanism. Endocannabinoids were measured in plasma, and they act in the brain. The study does not establish — and cannot establish — a direct “this much anandamide in the blood means this much euphoria” link.

The samples are small. 19 and 36 people, with no randomisation across distances: those who chose 230 km differ from those who chose 100.

Walking raised AEA too — gradually. So it is not about a “threshold of intensity beyond which the reward switches on”, as the story is usually told.

Reported euphoria is a subjective scale filled in after a race lasting many hours, when a person is exhausted, dehydrated and wants to sit down. The absence of a rise at the ultra may reflect physical state rather than the absence of a neurochemical response.

How to apply this

Do not expect the “high” as a reward for volume. The highest euphoria ratings in these data belong to the marathon, not to the longest distances. After 100+ km the typical response is less anxiety, but not a lift in mood.
If you run for the state rather than the result, a long steady run at moderate intensity is the working recipe: it is in exactly this mode that anandamide rises gradually and stays elevated for at least another 45 minutes after you stop.
Walking works too, just more slowly and more weakly. For recovery days that is a decent argument for not staying at home.
Pain in a marathon switches on at around the 28th kilometre — that is a group average, but a useful landmark when planning your pacing: the fact that things get psychologically harder after 30 km is not a failure of character. Build it into your race plan.
Do not take other people's stories about a “second wind” personally: individual variation in these studies is large, and some runners report no pronounced high at all.

The bottom line

The runner's high most likely rests on endocannabinoids rather than endorphins: blocking opioid receptors with naltrexone in 63 people prevented neither the euphoria nor the drop in anxiety.
In a marathon anandamide rises progressively every 14 km and stays elevated for another 45 minutes after the finish; walking of the same duration produces a weak response.
2-AG rises later — at the end of the run and in early recovery — and in ultrarunners only after the race.
After ultramarathons of 100–230 km anxiety falls and pain rises, but euphoria does not change significantly: the biochemistry and the sensations diverge, and that is the study's main honest result.

Sources: Siebers M., Huvermann D., Siebers C. et al. “Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies”. BMC Medicine, 2026. DOI: 10.1186/s12916-026-05186-z · Siebers M., Biedermann S.V., Bindila L., Lutz B., Fuss J. “Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans”. Psychoneuroendocrinology, 2021;126:105173. DOI: 10.1016/j.psyneuen.2021.105173 · Fuss J., Steinle J., Bindila L. et al. “A runner's high depends on cannabinoid receptors in mice”. Proceedings of the National Academy of Sciences, 2015;112(42):13105-13108. DOI: 10.1073/pnas.1514996112 · Boecker H., Sprenger T., Spilker M.E. et al. “The Runner's High: Opioidergic Mechanisms in the Human Brain”. Cerebral Cortex, 2008;18(11):2523-2531. DOI: 10.1093/cercor/bhn013