DATE: October 25, 2026 at 06:00AM
SOURCE: PSYPOST.ORG
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TITLE: Your body makes its own cannabis-like chemicals as you run, and neuroscience research finds they keep rising all the way to the marathon finish line, a possible clue to the runner’s high
A long run appears to keep the body’s own cannabis-like chemical messengers active for hours. New research published in BMC Medicine indicates that one of these compounds, anandamide, climbs steadily during a marathon and stays elevated 45 minutes after the finish, and that levels are also higher after ultramarathons of up to 230 kilometers. These chemical changes occurred alongside shifts in mood, such as reduced anxiety after running, although the study did not test whether one caused the other.
The runner’s high is a state some people report during or after endurance exercise, marked by euphoria, reduced anxiety, less pain, and a sense of calm afterward. Early explanations credited endorphins, the body’s natural opioid painkillers, but endorphins are large, water-soluble molecules, and there is no convincing evidence that they cross the blood-brain barrier, the protective filter between the bloodstream and the brain, in meaningful amounts.
Endocannabinoids offer an alternative: they are small, fat-soluble molecules made on demand from cell membranes, they can cross that barrier, and they act on the same cannabinoid receptors targeted by THC, the main psychoactive compound in cannabis. The two best studied are anandamide and 2-arachidonoylglycerol, often shortened to 2-AG.
Laboratory experiments began supporting this shift in thinking when a 2015 animal experiment led by Johannes Fuss, the senior author of the new study, showed that wheel-running mice relied on cannabinoid receptors, rather than opioid receptors, to experience reduced anxiety and lower pain sensitivity. Human research soon followed, including a 2021 clinical trial by the same group where researchers gave participants a medication that blocked opioid receptors. The runners still reported the typical calm and euphoric sensations of a runner’s high, suggesting that endorphins were not required for those effects.
In a 2022 systematic review, the same group found that 14 of 17 studies detected a rise in endocannabinoids after a single bout of exercise. But as the authors of the new study note, nearly all of that human research involved workouts lasting under an hour, leaving open what happens during true long-distance events.
“Humans are capable of running for many hours, sometimes even days, and we wanted to understand what happens to the endocannabinoid system during such extraordinary endurance efforts,” lead author Michael Siebers, a psychiatrist at LVR University Hospital Essen, told PsyPost.
“I believe that our ability to run long distances cannot be explained by anatomy alone,” Siebers explained. “We probably also need an entire orchestra of neuromodulators that reward us for sustained physical activity and help us continue running despite fatigue and discomfort. Thanks to a wonderful collaboration with researchers from Ulm and the German Sport University Cologne, we were able to investigate these processes during marathon and ultramarathon running, including distances of up to 230 kilometers.”
To investigate these biochemical and emotional shifts under real-world conditions, Siebers and his colleagues, including senior author Johannes Fuss of the University of Duisburg-Essen and collaborators at University Hospital Ulm and the German Sport University Cologne, designed two field studies of trained endurance athletes.
The first investigation examined 19 experienced runners, including seven women and 12 men, who completed a marathon course consisting of three 14-kilometer loops around Lake Baldeney in Essen, Germany. To establish a realistic comparison, each runner returned one to two months later to complete an identical-duration walking session along the same route at their preferred pace. Blood samples were drawn at the start, at the 14-kilometer and 28-kilometer marks, immediately after the full course (about 43 kilometers), and after a 45-minute rest period. Alongside blood draws, participants completed visual rating scales to score their current levels of euphoria, anxiety, and physical pain.
The second investigation followed 36 athletes (16 ran 100 kilometers, 7 ran 160, and 13 ran 230) taking part in the TorTour de Ruhr, a non-stop ultramarathon in central Germany. These athletes, comprising 13 women and 23 men, provided blood samples and mood ratings before the race and shortly after crossing the finish line. In both studies, laboratory technicians measured several key lipids, including anandamide and 2-AG.
In the marathon study, levels of anandamide rose progressively across the entire run. By the mid-race mark, anandamide was higher during running than during walking, which produced only modest changes, and it remained higher 45 minutes after the marathon ended. Running was also far more intense, with runners averaging about 83 percent of their estimated maximum heart rate, compared with about 58 percent while walking. The compound 2-AG displayed a different trajectory, showing lower levels early in the run compared to walking, but climbing during the final kilometers and staying elevated during early recovery.
The ultramarathon runners exhibited similar biochemical patterns upon completing their races. Anandamide and 2-AG concentrations were both higher after the race across all three ultramarathon distances compared to pre-race baselines. In an exploratory comparison, post-race anandamide levels after the marathon were nearly double those seen after the ultramarathons (32.4 versus 17.1 in the study’s measurements), which the authors suggest may reflect the higher running intensity of the shorter race.
Mood ratings also shifted during running. Marathon participants reported higher euphoria while running than while walking at several points, although at the 28-kilometer mark, a stage where runners often describe “hitting the wall,” euphoria was no longer different from walking. Anxiety ratings started slightly higher before the marathon than before the walk, then fell toward the end of the run, and pain ratings showed little change after 14 kilometers but rose markedly from 28 kilometers on. In the ultramarathon group, anxiety decreased after the race, more so at 100 and 160 kilometers than at 230, while pain rose and euphoria did not change in a statistically significant way.
When asked afterward, only 3 of the 19 marathoners said they had experienced a runner’s high during the marathon, while 8 said they had not and 8 were unsure; among the ultramarathoners, 12 said they had and 19 said they had not.
The findings are in line with research covered by PsyPost in 2022, which found that acute exercise consistently increased endocannabinoid levels, especially anandamide, with moderate intensity yielding stronger boosts than low intensity.
“This is an interesting study, particularly because it’s not easy to investigate physiological responses to exercise over marathon and ultramarathon distances,” said Danielle McCartney, a research affiliate at the University of Sydney who was not involved in the study. “The key finding is that circulating concentrations of anandamide (AEA), an endocannabinoid, increased progressively throughout the marathon and were also elevated following ultramarathons of 100, 160 and 230 km.”
“Previous studies have consistently shown that moderate-intensity running increases blood concentrations of AEA,” McCartney told PsyPost. “However, most of this research has focused on relatively short bouts of exercise (less than 60 minutes). This study fills an important gap by examining much longer running distances, and shows that increases in AEA also occur during marathon and ultramarathon running.”
The researchers see the sustained activity as a possible clue to how humans manage hours of running.
“One of our most important findings is that the body’s own cannabinoid system remains active even during extremely prolonged exercise,” Siebers noted. “We observed substantial increases in endocannabinoids, particularly anandamide, not only during marathon running but also after ultramarathons lasting many hours.”
“These molecules are sometimes described as the body’s own cannabis-like substances because they act on the same cannabinoid receptor system targeted by THC,” he said. “They may contribute to the rewarding, calming, and potentially pain-modulating effects of running. From an evolutionary perspective, I find this particularly fascinating. Humans have an extraordinary capacity for endurance running, and the endocannabinoid system may be one of the biological mechanisms that make prolonged running not only physically possible but also psychologically rewarding.”
Siebers described the shift many runners report over the course of a run.
“At the beginning of a run, everything may feel uncomfortable,” he observed. “Your calves are aching, your back feels stiff, and every step requires some effort.”
“But after a while, something can change,” he noted. “Your movements become smoother, running feels increasingly effortless, and you may enter a state of flow. Sometimes this develops into euphoria, while everyday worries and stress seem to fade into the background.”
Siebers also sees potential relevance for mental health.
“As a psychiatrist, I find this especially interesting because running can become a valuable tool for coping with stress, improving mood, and supporting mental well-being,” he added. “Of course, exercise is not a replacement for professional treatment when it is needed, but for some people, it can be an important part of their recovery and everyday life.”
The study did not test whether runners whose anandamide rose the most felt the most euphoric or calm.
McCartney cautioned, however, against assuming that these chemical increases directly generate the emotional sensations reported by participants. “It’s important to recognize that this study doesn’t establish that increases in AEA are responsible for the ‘runner’s high,'” she explained. “It shows that prolonged running increases blood AEA concentrations and is associated with changes in mood, including increased euphoria and reduced anxiety. While these findings are consistent with the idea that AEA contributes to the runner’s high, they don’t establish a causal relationship.”
The TorTour de Ruhr presented extreme physical demands, requiring runners to navigate unfamiliar routes for up to 230 kilometers, often through the night and in isolation.
“What impressed me most was witnessing what humans are capable of achieving,” Siebers recounted. “Some of our participants ran distances of up to 230 kilometers, maintaining their effort for many hours, sometimes running alone through the night on unfamiliar trails. Equally fascinating was the atmosphere among the ultramarathon runners. Despite the enormous physical demands, there was a remarkable sense of community and positivity.”
“I was particularly struck by participants who reported very little anxiety after these extraordinary distances, even after spending hours alone in unfamiliar surroundings,” he said. “Some runners also reported surprisingly little pain despite covering distances that would seem almost unimaginable to most people. These observations make me wonder how strongly our internal neuromodulatory systems can influence the way we experience physical effort, pain, and fear.”
Pain was still common: 29 of the 36 ultramarathoners reported pain during the race, only five reported none, and eight said they used pain medication, particularly in the longest race.
As with all research, there are some caveats to consider. The marathon study used walking as a comparison rather than having participants sit quietly, meaning the control condition still involved mild physical exertion. Participants also selected their own running and walking speeds, which preserved a realistic race environment but introduced variation in how hard each individual was working.
“I have reasonable confidence in the main findings, particularly because the increases in AEA were consistent across the marathon and ultramarathon studies and align with previous research,” McCartney told PsyPost. “However, there are some limitations worth considering. Measuring endocannabinoids in blood can be technically challenging, and although the authors used established analytical methods, they don’t explicitly report whether these methods were validated.”
“I’d also have liked more information about what participants ate during and after exercise,” McCartney added. “We know that nutrient intake can influence blood AEA concentrations, so it’s possible that dietary behavior affected the measures.”
The authors describe their laboratory analysis as following established, standardized protocols, including adding chemically labeled reference versions of each compound to every sample to allow exact measurement. They also acknowledge that participants’ nutrition, rest, and time of day were not fully controlled.
Every participant also ran the marathon before doing the walking session, which the authors note may have raised anxiety at the start of the running day. The samples were also small, with 19 marathoners and between 7 and 16 runners at each ultramarathon distance, and no blood was drawn during the ultramarathons themselves.
The emotional measures relied on brief, single-item rating scales, which capture only a snapshot of complex mental states like flow or emotional relief. Logistics during the ultramarathon also meant that pre-race samples for the 230-kilometer group had to be collected the previous evening rather than right at the starting line.
“One important distinction is that we measured endocannabinoids in the blood, not directly in the brain,” Siebers pointed out. “Although our findings show substantial changes in circulating endocannabinoid concentrations, we cannot yet determine precisely what happens in the brain during prolonged running.”
“Another important point is that the runner’s high is not simply caused by one molecule,” he added. “Endocannabinoids are probably part of a much larger and highly complex orchestra of neuromodulators, including dopamine, serotonin, endogenous opioids, and other signaling systems. Furthermore, not everyone experiences a runner’s high, and running does not necessarily become more enjoyable the longer someone continues.”
When considering future research, McCartney highlighted both pharmacological and nutritional avenues for follow-up testing. “Ideally, I’d like to see whether blocking cannabinoid receptors prevents the runner’s high,” she said. “Unfortunately, the safety concerns associated with drugs like rimonabant make that a difficult experiment to conduct in humans!”
Rimonabant, a drug that blocks the main cannabinoid receptor, was pulled from the European market in 2008 after it was linked to depression and suicidal thoughts.
“More realistically, I’d be interested in seeing whether nutrition influences the endocannabinoid response to prolonged exercise,” McCartney told PsyPost, “particularly given that runners typically consume substantial amounts of carbohydrate during marathon and ultramarathon events.”
Looking ahead, the authors hope to examine how these chemical messengers operate directly within the central nervous system during physical exertion.
“One of my main interests is understanding how running influences mood changes and the brain itself,” Siebers said. “So far, our research has primarily focused on measuring endocannabinoids in peripheral blood. However, the runner’s high ultimately involves processes within the central nervous system, and we still know surprisingly little about what actually happens in the human brain during running. I would therefore like to investigate these central mechanisms more directly, potentially through neuroimaging and other methods that allow us to study neuromodulation in the brain.”
“In addition, I am particularly interested in how the endocannabinoid system interacts with pain regulation during prolonged exercise,” he continued. “Why can some individuals continue running for hours despite considerable physical stress, while others experience increasing discomfort? Understanding these mechanisms could provide valuable insights not only into endurance exercise but also into pain regulation and mental health.”
Beyond laboratory measurements, the researchers also reflected on the broader personal and evolutionary dimensions of sustained running.
Siebers emphasized that the effect requires no outside substance. “What fascinates me is that our bodies can produce their own cannabis-like substances simply through physical activity,” he told PsyPost. “Under the right circumstances, this can contribute to a completely natural high, without consuming any external substance.”
“For me, the most exciting message is that running is much more than moving our legs,” Siebers said. “It is a fascinating interaction between our body and brain, and understanding this interaction may help us discover why humans have developed such an extraordinary relationship with endurance running.”
The study, “Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies,” was authored by Michael Siebers, Dana Huvermann, Christoph Siebers, Deborah Canales-Romero, Alexandra Florea-Ghile, Lina Keite, Lucas John, Moritz Munk, Roman Bizjak, Jens Witzel, Sebastian Schulz, Johannes Kirsten, Laura Bindila, Anke Hinney, Marijke Grau, Daniel A. Bizjak, Harald Engler, and Johannes Fuss.
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