What may be the earliest known evidence of human drug use suggests that it occurred 25,000 years ago, according to findings by archaeologists that push back on earlier estimates by over 10,000 years.

In a recent paper published in Science Advances, an international team of researchers led by Professor Adam Brumm from Griffith University’s Australian Research Center for Human Evolution (ARCHE) discovered betel nut residue on ancient teeth in Indonesia. 

Betel nuts are an addictive stimulant popular throughout the Asia-Pacific region, which researchers previously believed only came into use about 3,500 years ago. Globally, archaeologists had believed psychoactive drugs had been tied to the rise of agriculture.

Betel Nuts: the First Drugs

Archaeologists typically point to Israel’s brewing of fermented alcoholic drinks, such as those made of barley, as the earliest use of psychoactive drugs, roughly 13,000 years ago.

“However, this theory fails to account for the possibility that very ancient drug-taking lies at the roots of our most commonly used psychoactive substances,” Professor Brumm said.

Betel nuts are only regionally popular in India and the South Pacific, but their use is almost ubiquitous among the 10% of the world’s population that lives there. The psychoactive effects of the stimulant include enhanced alertness and mild euphoria.

The betel nut is the seed of the Areca catechu palm. Locals burn its shell, then grind it into a fine powder and mix it with slaked lime, another powder made from quicklime and water. They mix these powders with other minor ingredients, wrap them in a betel leaf, and chew them to produce a mild altered state.

Research on the drug suggests that this processing releases Arecoline, the neuroactive alkaloid present in the betel nut, in a more bioavailable form. Modern usage is linked to cancer, gum disease, and tooth decay, making it a significant public health problem in regions where it is used.

A Prehistory of Betel Nut Usage Uncovered

The seeds were rarely preserved in archeological sites, creating a great deal of uncertainty about the drug’s early history.

Human remains used in the study came from Sulawesi, one of the islands that make up Indonesia. There, archeologists uncovered two hunter-gatherer skeletons: one dating to 7,600 to 6,300 years old and the other 25,000 to 16,000 years old.

These skeletons carried an unusual signal, which the team interpreted as related to ancient drug use. Their teeth had deep, rounded grooves that the researchers believe developed from the habit of sucking on whole betel nuts. Biochemical analysis further supported this interpretation by identifying Arecoline in the remains’ dental tissues.

“But our team conducted experiments in which we soaked betel nuts in artificial saliva and tested the resultant broths against a panel of cloned human receptors expressed in frog egg cells, including specialized proteins that act as molecular switches, regulating neural activity,” said lead author Professor Adam Brumm. “This showed that just sucking on intact betel nuts will release Arecoline in sufficient amounts to have a physiological effect, altering brain function.”

Rethinking Prehistory

This crude attempt to use the betel nuts as a drug likely produced a milder high, while also promoting periodontal disease. Given the poor state of the teeth in human remains previously found on the island, the team believes the betel nuts may have initially been used as a toothache remedy, though it was a poor choice for that purpose.

“Over time, however, sucking these hard, abrasive seeds wore down the foragers’ teeth so badly that in some cases the inner pulp chamber became completely exposed – this would have been extremely painful, caused difficulty eating, and greatly increased the rate of chronic tooth infection,” Professor Brumm said. “So while this habit may have been a remedy for toothache, years of prolonged nut-sucking eventually caused much worse dental health problems, creating a cycle of continued habitual use.”

Pushing back the use of these psychoactive substances so far significantly rewrites our understanding of human drug history.

“Emerging by up to 25,000 years ago in Sulawesi, thus long preceding the onset of agriculture, betel nut-sucking may be the earliest evidence for drug use anywhere in the world,” Professor Brumm concluded. “By identifying the ancient practice underlying betel-nut chewing as we know it, the study implies that some modern drug-taking behaviors are deeply rooted in forager traditions.”

The paper, “Betel Nut Sucking is the Earliest Recorded Evidence for the Habitual Use of a Neuroactive Plant Drug,” appeared in Science Advances on September 9, 2026.

Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.

Two skeletons from the Indonesian island of Sulawesi had something strange going on in their mouths. Not cavities. Not the usual wear from a tough diet. Deep, rounded grooves cut into the teeth — a pattern no archaeologist had documented before, and one nobody could explain. The answer, published in Science Advances, pushes the known […]

A team of archaeologists has discovered in northern Turkey a settlement of hunter-gatherers who lived in the Koskarlı cave approximately 14,000 years ago. The remains found during the first excavation campaign, conducted in 2024, confirm that the site was inhabited by human groups during the Epipaleolithic period, a transitional stage between the Upper Paleolithic and […]

Around 70% of the animals were female,

A longstanding archaeological mystery has loomed over discoveries at ancient burial sites in eastern Siberia: why were so many children and adolescents among the dead?

Now, according to a recent study in the journal Nature, DNA recovered from human remains found in burial sites at four cemeteries near Lake Baikal in eastern Siberia may finally reveal the answer.

Thousands of years ago, prior to the rise of ancient medieval cities—and their often-rat-infested streets—a disease famously associated with these rodents had already ravaged communities of prehistoric hunter-gatherers.

The research, based on reconstructions of ancient bacterial genomes preserved in the teeth of these ancient Siberians, revealed the presence of previously unknown strains of Yersinia pestis—the bacteria responsible for plague—providing fresh evidence that the lethal disease was already manifesting and killing human populations at least as far back as 5,500 years ago.

“Whether the earliest forms of plague were mild or virulent has been a matter of debate, but our findings demonstrate that these ancient strains were already highly lethal,” said senior author Eske Willerslev of the University of Copenhagen and the University of Cambridge.

New Evidence of an Ancient Siberian Plague

In their study, the team successfully located plague DNA in 18 out of 46 individuals they studied. Based on radiocarbon dating, many of the deaths were confirmed to have all happened within a short span of time, which is consistent with sudden deaths resulting from plague. Additionally, genetic evidence showed that several of these victims had been close relatives.

One key finding in the research involved the number of children and adolescents who were among the dead—a discovery mirroring earlier findings at prehistoric sites in the region, which had remained a longstanding archaeological mystery.

“The unusually high number of children and the short timespan was a real puzzle that we’ve been trying to solve since the 1990s,” said archaeologist Andrzej Weber of the University of Alberta. “Finding out that plague was the cause is extraordinary, but it makes so much sense.”

New Findings Challenge Old Assumptions

Based on the new findings, ancient strains of plague appear to have been more harmful than once thought. In the past, it was presumed that because these early strains lacked genetic adaptations that helped the bubonic plague spread so efficiently through fleas and rodents, they were relatively harmless.

The team’s research now reveals that these newly identified strains carried a specific toxin-producing genetic feature, known as a superantigen, which can trigger severe immune responses that potentially had devastating impacts on mortality rates in the ancient world.

Such deadly outbreaks may have had a far more significant impact on ancient human populations than previously realized, and during periods long before the rise of major urban centers and organized agriculture.

In terms of the origins of the disease, researchers believe that they may have finally traced it to Central or Northeast Asia, where infections may have spread from marmots, large rodents that are still recognized as plague carriers in modern times.

After years of uncertainty, the team’s research offers some of the best evidence to-date that one of the most devastating diseases in human history was already playing a role in shaping human history thousands of years earlier than once thought.

Martin Sikora, associate professor at the University of Copenhagen and the study’s senior author, says his team’s research “changes our understanding of the earliest plague outbreak,” and now confirms that such ancient strains “appear to have carried a potent combination of virulence factors that could make infection highly lethal.”

The team’s study, “Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago,” appeared in the journal Nature on June 17, 2026.

Micah Hanks is the Editor-in-Chief and Co-Founder of The Debrief. A longtime reporter on science, defense, and technology with a focus on space and astronomy, he can be reached at micah@thedebrief.org. Follow him on X @MicahHanks, and at micahhanks.com.

A century after they were discovered, they're finally getting some appreciation.