25,000-year-old teeth may reveal the world’s earliest evidence of drug use

  • Two hunter-gatherers from Sulawesi show unusual rounded grooves worn deeply into their teeth, while chemical analysis detected arecoline, the main psychoactive alkaloid associated with areca, or betel, nuts.
  • The older individual lived between about 25,000 and 16,000 years ago, potentially pushing direct evidence for habitual use of a neuroactive plant thousands of years earlier than previously documented examples.
  • Experiments found that intact areca nuts can release physiologically active compounds without being chewed with slaked lime, supporting the idea that these foragers repeatedly sucked whole nuts despite severe long-term dental damage.

A peculiar set of grooves worn into ancient human teeth may record a behavior almost unimaginable from bones alone.

Hunter-gatherers living on the Indonesian island of Sulawesi thousands of years before farming appear to have habitually held and sucked hard areca nuts in their mouths. The practice released enough of the stimulant arecoline to affect the nervous system, while years of repeated use left deep, rounded scars across their teeth.

The discovery could push direct evidence of habitual psychoactive plant use back as far as 25,000 years.

Researchers led by Griffith University combined archaeology, dental analysis, chemistry and receptor experiments for the study, “Betel nut sucking is the earliest recorded evidence for the habitual use of a neuroactive plant drug,” published in Science Advances. The team included scientists from Griffith’s Australian Research Centre for Human Evolution and Indonesian researchers from Hasanuddin University and the National Research and Innovation Agency.

Lead author Professor Adam Brumm.
Lead author Professor Adam Brumm. (CREDIT: Griffith University)

“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,” said Griffith archaeologist Adam Brumm.

Strange grooves pointed to a long-lasting habit

The evidence came from two exceptionally rare prehistoric individuals.

One, designated Maros-LBB-1a, came from Late Pleistocene deposits at Leang Bulu Bettue and dates to between 25,000 and 16,000 years ago. The second, CPL-R2a, came from Leang Cappalombo 1 and lived roughly 7,600 to 6,300 years ago.

Both showed an unusual form of dental wear.

Instead of the flatter surfaces expected from ordinary chewing, their teeth contained deep circumferential grooves. Some appeared rounded as though a hard object about 10 to 20 millimeters wide had repeatedly rested between the teeth.

The wear occurred at different positions around the mouth, suggesting the object was routinely moved from one location to another.

The researchers concluded that whole, dehusked seeds from wild Areca palms offered a plausible match. Areca triandra, a wild species native to South Sulawesi, produces seeds compatible with the estimated size of the objects responsible for the wear.

The schematic illustration depicts the preferred positions of whole betel nuts held in the mouths of the Late Pleistocene forager (Maros-LBB-1a) and middle Holocene forager (CPL-R2a), as inferred from dental wear analysis.
The schematic illustration depicts the preferred positions of whole betel nuts held in the mouths of the Late Pleistocene forager (Maros-LBB-1a) and middle Holocene forager (CPL-R2a), as inferred from dental wear analysis. (CREDIT: Shutterstock / Science Advances)

Importantly, the teeth lacked the characteristic staining associated with conventional betel quid chewing.

A simpler practice came before modern betel chewing

Today, areca nut is commonly consumed as part of betel quid.

A typical preparation combines pieces of Areca catechu seed with slaked lime and often a leaf from the betel vine, Piper betle. The alkaline lime changes the chemistry of areca alkaloids and increases their bioavailability.

Arecoline, one of the nut’s major neuroactive compounds, acts on acetylcholine receptors. Consumption can produce increased alertness, mild euphoria and other physiological effects.

Archaeologists had previously traced relatively secure biomolecular evidence for betel use to much later periods. The Sulawesi remains suggest something different may have preceded the prepared quid.

Rather than chopping or grinding the nuts, these hunter-gatherers may simply have kept whole seeds inside their mouths and sucked or gently gnawed them for prolonged periods.

That raised a critical question. Would an intact nut actually release enough psychoactive material to matter?

Historical distribution of betel chewing and elements of the betel quid.
Historical distribution of betel chewing and elements of the betel quid. (CREDIT: Adam Brumm et al, Science Advances)

Frog egg cells helped test the ancient behavior

To answer that question, the researchers recreated part of the process experimentally.

They soaked intact and broken areca nuts in physiological solutions, producing liquid extracts representing compounds that could escape while a nut sat in the mouth.

Those extracts were then applied to frog egg cells engineered to express human receptors involved in nervous-system signaling.

Solutions from intact nuts triggered responses in human M1 and M3 muscarinic acetylcholine receptors. The results showed that low-molecular-weight substances, including arecoline, could escape from whole nuts without the processing involved in modern betel quid.

The researchers concluded that sucking an intact areca nut could release enough arecoline to cause physiological effects.

Not every component escaped equally. For example, the experiments found no detectable activation associated with gamma-aminobutyric acid, or GABA, from intact nuts.

That suggests ancient nut sucking was chemically different from chewing a processed betel quid, even if both delivered neuroactive compounds.

Betel nut fruits with a dehusked betel nut in foreground.
Betel nut fruits with a dehusked betel nut in foreground. (CREDIT: Adam Brumm)

The chemicals were still inside ancient teeth

The strongest evidence came directly from the archaeological remains.

Researchers analyzed tooth samples using liquid chromatography-mass spectrometry, a technique capable of separating and identifying chemical compounds.

Arecoline was detected in dental material from Maros-LBB-1a, the Late Pleistocene individual. It was also identified in a tooth from CPL-R2a.

Those results provided biochemical evidence that both people had consumed areca nuts.

The team also found other plant compounds, some associated with Piper betle leaves. However, several chemicals expected to become more abundant when areca nut is combined with slaked lime were absent or undetectable.

Together with the absence of classic betel staining, the pattern supports the researchers’ proposal that these individuals were sucking whole nuts rather than consuming a modern-style quid.

The conclusion still rests on only two people. Human skeletal remains from preagricultural Sulawesi are exceptionally scarce, making it impossible to know how widespread the practice was.

(A and B) Right maxilla fragment with three molars (M1 to M3) from a Late Pleistocene individual (Maros-LBB-1a); (A) right lateral view; (B) left lateral view. (C to H) Maxillary [(C) to (F)] and mandibular [(G) to (H)] dentition of a Middle Holocene individual (CPL-R2a). Both are middle to old adults.
(A and B) Right maxilla fragment with three molars (M1 to M3) from a Late Pleistocene individual (Maros-LBB-1a); (A) right lateral view; (B) left lateral view. (C to H) Maxillary [(C) to (F)] and mandibular [(G) to (H)] dentition of a Middle Holocene individual (CPL-R2a). Both are middle to old adults. (CREDIT: Adam Brumm et al, Science Advances)

A painkiller that may have made the pain worse

The habit appears to have come with a serious cost.

Both individuals had poor oral health. Years of holding hard, abrasive seeds between their teeth produced severe wear, periodontal disease and tooth loss.

In CPL-R2a, the damage became so extreme that parts of the tooth pulp cavities were exposed, creating opportunities for chronic infection and intense pain.

That presents a striking possibility because arecoline itself has analgesic properties.

The researchers suggest the nuts may sometimes have been used to relieve tooth pain. But repeatedly sucking the hard seeds could then worsen dental damage, potentially encouraging continued use for relief.

“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,” Brumm said.

The study cannot determine whether these individuals experienced addiction in the modern clinical sense, or whether medicinal use, stimulation, ritual behavior or several motivations drove the practice.

Drug use may predate farming by millennia

The broader implication reaches far beyond two sets of damaged teeth.

Some of the oldest previously recognized psychoactive traditions include fermented barley drinks dating to roughly 13,000 years ago. That evidence helped reinforce the idea that habitual drug use expanded alongside settled agricultural societies.

The Sulawesi discovery challenges that timeline.

If the interpretation is correct, hunter-gatherers were deliberately and repeatedly consuming a neuroactive plant long before agriculture transformed human societies.

“By identifying the ancient practice underlying betel-nut chewing as we know it, the study implies that some modern drug-taking behaviours are deeply rooted in forager traditions,” Brumm said.

The evidence does not reveal when humans first discovered psychoactive plants. It instead captures something archaeology rarely preserves: a repeated behavior, its chemistry and even some of its physical consequences.

Twenty-five thousand years later, the evidence may still be visible in the grooves worn into human teeth.

Dig deeper into betel nut, psychoactive plants and ancient drug use

These resources provide archaeological, pharmacological and public-health context for understanding areca nut use and its long history.

Earliest direct evidence of bronze age betel nut use: biomolecular analysis of dental calculus from Nong Ratchawat, Thailand: Chemical analysis of roughly 4,000-year-old dental calculus identified arecoline-related compounds, demonstrating how biomolecular archaeology can reveal betel use even without characteristic tooth staining. (Frontiers in Environmental Archaeology, 2025)

Pharmacological and biological activities of areca nut (Areca catechu L.): A systematic review: Reviews recent evidence on areca nut chemistry, physiological activity and biological effects, providing modern context for the neuroactive plant investigated archaeologically. (Journal of Food Measurement and Characterization, 2026)

Metabolism of the areca alkaloids – toxic and psychoactive constituents of the areca (betel) nut: Examines arecoline, arecaidine and related alkaloids, including how these psychoactive and toxic compounds are metabolized. (Drug Metabolism Reviews, 2022)

Research findings are available online in the journal Science Advances.

The original story “25,000-year-old teeth may reveal the world’s earliest evidence of drug use” is published in The Brighter Side of News.


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