Ancient remains from two hunter-gatherers on Indonesia’s Sulawesi island suggest that people may have used a mind-altering plant substance thousands of years earlier than previously recognized.

The betel nut, the seed of the areca palm, is regarded as the world’s fourth most commonly used psychoactive substance, after caffeine, alcohol and nicotine.

Today, roughly one in 10 people, mainly in parts of Asia and the Pacific, continue the custom of chewing a quid made from processed betel nut and slaked lime.

Slaked lime, or calcium hydroxide, prompts a chemical process that speeds the movement of arecoline, the nut’s psychoactive compound, into the bloodstream. Chewing the mixture can produce slight euphoria and greater alertness.

But how far back does human experimentation with psychoactive substances really extend?

“Archaeologists have traditionally thought the first drug-use practices emerged around 13,000 years ago, when mobile hunter-gatherers began domesticating plants and settling into farming communities,” said Adam Brumm, an archaeology professor at Griffith University’s Australian Research Centre for Human Evolution.

In this period, often called the Neolithic Revolution, people in the region of present-day Israel began producing beer from barley. Earlier evidence also indicated that betel nut chewing was practiced in Southeast Asia by at least 4,000 years ago.

But Brumm and his colleagues have found signs that prehistoric foragers may have sucked whole betel nuts as long ago as 25,000 to 16,000 years ago. If correct, the behavior could be the oldest known example of human drug use and may represent an early form of the custom that still survives today.

Brumm, lead author of a study published in the journal Science Advances, said the whole nuts were probably weaker than modern quids. Even so, they may have been used to dull pain while eventually creating serious dental problems.

“The discoveries from Sulawesi indicate that some foraging groups were using plant-based drugs much earlier than expected,” Brumm said. “They may also have developed dependence on their neurological effects and suffered the harms of long-term consumption.”

Fossils with stories to tell

In 2017, Brumm’s research group uncovered human remains at Leang Bulu Bettue, a limestone cave in the rugged Maros-Pangkep karst region of South Sulawesi.

A fragment of upper jaw belonged to an adult preagricultural forager who lived between 25,000 and 16,000 years ago. Three teeth remained in place, and two of them contained striking deep, rounded grooves.

Human remains rarely survive well in tropical settings such as Sulawesi, making the fragment an especially valuable discovery.

At another cave, Leang Cappolombo, located about 20.5 miles, or 33 kilometers, away, a separate team found another adult forager with similar grooves on the teeth. That individual dated to between 7,600 and 6,300 years ago. Although the remains were also discovered in 2017, Brumm’s team only began examining them several years later.

Researchers estimated that both people were at least 35 years old when they died, and possibly considerably older.

The unusual wear pattern did not match the marks typically associated with chewing betel nut. Instead, the researchers concluded that the grooves were probably made through repeated sucking on hard, rounded objects, including whole betel nuts.

Tests of dental tissue also revealed traces of arecoline, the principal pain-relieving chemical contained in betel nuts.

“These foragers had very poor oral health, so sucking the nuts may have been a customary treatment for tooth pain,” Brumm said. “Yet the seeds themselves are hard and abrasive. Prolonged, repeated sucking gradually wore down their teeth until the sensitive pulp chamber, the living center of the tooth, was exposed.”

Exposed pulp would have caused severe pain, made eating difficult and increased the likelihood of infections reaching the tooth roots and jawbone, Brumm said.

“We suspect that some people became pathologically dependent on betel nut sucking as a way of treating pain caused by the same practice,” he said. “It may have become a self-perpetuating cycle.”

Because whole nuts lack the powerful activating effect of slaked lime, the scientists also wanted to determine whether they could still alter the brain.

The researchers soaked betel nuts in laboratory-made saliva, consisting of saline fluid and food-digesting enzymes, for biochemical testing. They then exposed cloned human receptors, including proteins involved in neural activity, to the resulting liquid. The receptors had been placed within frog egg cells.

“The experiment showed that sucking intact betel nuts can release enough arecoline to produce a physiological response and affect brain function,” Brumm said.

Uncovering ancient substance-use traditions

The study’s authors believe betel nut sucking was an enduring cultural practice among foraging communities for many thousands of years.

“These findings place betel nut use in a very different social setting,” said Dr. Mario Zimmermann, an archaeologist and paleoethnobotany specialist at Boise State University. Paleoethnobotany uses ancient plant evidence to understand how past populations used different species. Zimmermann was not involved in the research but reviewed the study during publication.

“Earlier work from our group identified use in a Bronze Age society with clear social hierarchy,” Zimmermann said.

The new evidence, however, suggests regular betel nut use among people living in more egalitarian hunter-gatherer societies, he added.

The researchers propose that the practice later developed into betel nut chewing around 4,000 years ago, when Austronesian settlers arrived in Sulawesi during the spread of farming populations from Taiwan.

“We think Austronesian farmers may have seen Sulawesi’s original inhabitants sucking betel nuts, adopted the practice and added their own innovation: chewing the nuts with slaked lime,” Brumm said. “Those early farming communities also used lime in pottery-making.”

Brumm personally tried sucking on a betel nut to better understand the possible experience of prehistoric users. He described it as “distinctly unpleasant” because of the sharp, astringent liquid released by the seed.

Still, he felt a numbing effect in his mouth, which may have given ancient foragers short-term relief from dental pain, even as the behavior contributed to worsening oral damage.

Zimmermann said the findings underline the long human history of consuming substances for reasons beyond nutrition.

“People do not consume things only to satisfy hunger or thirst,” Zimmermann said. “For tens of thousands of years, humans have used plants and animal products for pain management, stamina, social interaction and altered states of experience.”

Brumm now hopes to investigate how ancient other familiar substance-related practices may be.

“Fermented fruit can intoxicate animals as well as humans — birds do it too,” Brumm said. “I suspect foragers in many regions were creating and drinking fermented beverages long before Neolithic agriculture began around 13,000 years ago.”