The world's oldest known habitual drug use has been traced to Ice Age hunter-gatherers on the Indonesian island of Sulawesi, who sucked on betel nuts at least 25,000 years ago — thousands of years earlier than any previous evidence of a lasting drug habit.

Researchers found the clue in deep, distinctive grooves worn into the teeth of two prehistoric people whose partial skeletons were excavated on Sulawesi. The study, published Sept. 9 in the journal Science Advances, was led by Adam Brumm of Griffith University's Australian Research Centre for Human Evolution, working with colleagues from Makassar's Hasanuddin University and Indonesia's National Research and Innovation Agency.

The two individuals lived millennia apart. One, a man who died between the ages of 40 and 50, lived roughly 25,000 to 16,000 years ago, during the depths of the Last Glacial Maximum. The other, whose sex could not be determined, lived on the island between 7,600 and 6,300 years ago. Both bore the same damage — evidence that the practice was passed down across an enormous span of prehistory.

Betel nuts, the seeds of the areca palm, contain a neuroactive compound called arecoline. Chewed with slaked lime they act as a powerful stimulant; sucked directly, as these hunter-gatherers apparently did, they mostly numb the mouth. To test whether the practice had a genuine pharmacological effect, the team exposed genetically engineered frog eggs carrying human neuroreceptors to the nuts — and found that it did.

The habit appears to have started as self-medication. The grooves are consistent with repeatedly pressing a nut against aching teeth, and they worsened over time: in one individual the wear had reached the tooth's inner pulp cavity. "The more they sucked on the nut to relieve toothache, the worse that the damage to their teeth became," Brumm told Live Science, describing the resulting pain as excruciating.

The findings push the origins of betel nut use back from roughly 3,500 years ago — the previous earliest archaeological trace, found on the teeth of a person in Thailand — to the tail end of the last ice age. That challenges a long-standing theory that widespread psychoactive drug use emerged only after humans settled down to farm during the Neolithic, the era that also produced some of the earliest known alcoholic drinks, brewed from barley about 13,000 years ago.

Betel nut remains one of the most widely used psychoactive substances on Earth. After alcohol, caffeine and nicotine, it is the fourth most common, chewed daily by millions of people across the Asia-Pacific. Its modern reputation is double-edged: the same habit that may once have eased toothaches is now tied to high rates of mouth cancer. What the new study suggests is that the human relationship with mind-altering plants is far older — and far more entangled with ordinary survival — than the archaeological record had let on.

Sources: Live Science, The Conversation, ScienceDaily, The Debrief