One of the most popular mind-altering stimulants has prehistoric roots

The prehistoric remains of two foragers found on the Indonesian island of Sulawesi contain telltale signs that humans began using a mind-altering drug thousands of years earlier than known.

The betel nut, a fruit seed from the areca palm, is considered the fourth most widely used psychoactive substance in the world after caffeine, alcohol and nicotine.

About 1 in 10 people today, largely across Asia and the Pacific, practice the tradition of chewing a quid, or processed betel nut mixed with slaked lime.

The slaked lime, also known as calcium hydroxide, is essential for triggering a chemical reaction that expedites the absorption of the psychoactive compound arecoline into the bloodstream. Users experience mild euphoria and heightened alertness when chewing the quid.

Adam Brumm/Griffith University

But when did humans first begin experimenting with psychoactive substances?

“Archaeologists have long believed that the earliest traditions of drug use arose around 13,000 years ago when nomadic hunter-gatherers began to domesticate plants and live permanently in one place as farmers,” wrote Adam Brumm, professor of archaeology at Griffith University’s Australian Research Centre for Human Evolution, in an email.

During this so-called Neolithic Revolution , farmers in what’s now Israel first brewed beer from barley. And betel nut chewing occurred in Southeast Asia as early as 4,000 years ago , previous evidence has suggested.

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But Brumm’s team has uncovered evidence that prehistoric foragers were sucking on whole betel nuts between 25,000 and 16,000 years ago. The practice could represent the oldest known example of drug use by humans, which evolved into the betel nut chewing that remains so popular today.

Brumm, lead author of a new study published Wednesday in the journal Science Advances , and his colleagues believe that while less potent than quids, the whole betel nuts served as a pain reliever — but created a chain reaction that only led to more pain.

“The new findings from Sulawesi suggest foraging communities in some parts of the world were not just using plant drugs at a far earlier time,” Brumm said, “they were becoming dependent on their neuroactive properties and suffering from the negative consequences of long-term use.”

Brumm’s team unearthed a set of remains from Leang Bulu Bettue, a limestone cave in South Sulawesi’s mountainous Maros-Pangkep karst landscape , in 2017.

The upper jawbone fragment belonged to an adult, determined to be a preagricultural forager, who lived between 25,000 and 16,000 years ago. Three of the teeth were still preserved, and intriguingly, two had deep, rounded grooves, Brumm said.

Prehistoric remains don’t preserve well in tropical environments such as Sulawesi, making the jawbone a rare find.

A separate research team working about 20.5 miles (33 kilometers) away at a different cave site, Leang Cappolombo, found the remains of another adult forager with the same telltale grooves left on the teeth, but dated to between 7,600 and 6,300 years ago. The discovery was also made in 2017, but Brumm’s team did not get a chance to study the teeth until three years ago.

Both individuals were at least 35 years old, if not older, when they died, according to researchers.

The pattern of dental wear on the foragers’ teeth didn’t resemble previous evidence of betel nut chewing. Instead, the grooves were likely created due to habitual sucking on hard, round objects such as whole betel nuts, the researchers determined.

The team also analyzed the dental tissue and detected traces of arecoline, the main pain-relieving chemical compound from betel nuts.

“The foragers had poor dental health, so it is likely that nut-sucking was a traditional medicinal remedy for toothache,” Brumm said. “However, these hard round seeds are abrasive objects. Regularly sucking the nuts for prolonged periods gradually wore down the dentition of the users so severely that the sensitive inner pulp chamber, the ‘living core’ of the tooth, became exposed.”

The pain caused by the exposed pulp chambers would have been intense, leading to difficulty eating and inviting infection to spread to the teeth’s roots and even the jawbone, Brumm added.

“At this point, we suspect these people were pathologically addicted to betel nut-sucking to treat the oral pain caused by this cultural practice,” Brumm said. “In effect, they were trapped in a vicious cycle.”

Without potent slaked lime to activate the nut’s psychoactive high, Brumm and his team questioned what mind-altering effects the foragers might have experienced.

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The team soaked betel nuts in artificially created saliva — a saline solution combined with enzymes that help break down food — to carry out a biochemical analysis. The scientists tested the resulting “broths” against cloned human receptors — including proteins that regulate neural activity — that had been embedded in frog egg cells.

“This showed that just sucking on intact betel nuts will release arecoline in sufficient amounts to have a physiological effect, altering brain function,” Brumm said.

The study authors said sucking on betel nuts was a long-standing cultural practice rooted in forager traditions for thousands of years.

“The new data puts betel nut sucking into a very different social context,” wrote Dr. Mario Zimmermann, assistant clinical professor at Boise State University in Idaho and archaeologist specializing in paleoethnobotany, in an email. Paleoethnobotany relies on ancient plant remains to identify how people utilized different flora. Zimmermann did not participate in the new study, but he was a peer reviewer during the editorial process.

“Our team’s results from last year established early use in a Bronze Age hierarchical society,” Zimmermann said.

But the new study provides evidence for habitual use of betel nut among equals, he added.

The practice might have evolved into betel nut chewing 4,000 years ago when early Neolithic settlers called Austronesians colonized Sulawesi as farming societies expanded out of Taiwan, the study authors hypothesize.

Naoki Morimoto/KyotoU

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“We think that Austronesian farmers saw the original inhabitants of Sulawesi sucking betel nuts, adopted this practice for themselves, and introduced their own innovation: chewing the nuts with slaked lime,” Brumm said. “Notably, these early farmers used this substance to make pottery.”

Brumm tried sucking on a betel nut to see what it was like for prehistoric foragers and called the experience “distinctly unpleasant” due to the astringent liquid released in the process.

He did, however, experience a numbing sensation in his mouth, which would have provided the foragers with temporary relief from toothaches — even while causing damage to their dental health.

The research helps highlight how consuming nondietary substances has long been a part of the human experience, Zimmermann said.

“We don’t just ingest things to quench our thirst and hunger,” Zimmermann said. “For tens of thousands of years humans have been consuming plant and animal products for purposes such as pain relief, endurance, social lubricant, or the immersion in alternate realities.”

Now, Brumm wants to explore just how far back other common substance habits go.

“Getting drunk on fermented fruits is not even unique to humans — birds do it,” Brumm said. “I suspect that foragers in various parts of the world were making and consuming fermented beverages long before the advent of Neolithic farming around 13,000 years ago.”

在印度尼西亚苏拉威西岛发现的两名史前觅食者的遗骸包含明显的迹象，表明人类早在数千年前就开始使用一种改变精神状态的药物，比我们所知的要早得多。

槟榔，是槟榔树的果实种子，被认为是继咖啡因、酒精和尼古丁之后，世界上使用最广泛的第四种精神活性物质。

如今，大约十分之一的人，主要分布在亚洲和太平洋地区，仍然保留着嚼槟榔（一种加工过的槟榔与熟石灰混合而成的食品）的传统。

熟石灰，也称氢氧化钙，是引发化学反应的必需物质，该反应能加速精神活性化合物槟榔碱被血液吸收。咀嚼槟榔后，使用者会感到轻微的欣快感和高度警觉。

亚当布鲁姆/格里菲斯大学

但人类最早是什么时候开始尝试使用精神活性物质的呢？

“考古学家一直认为，最早的药物使用传统大约出现在 13000 年前，当时游牧的狩猎采集者开始驯化植物，并作为农民在一个地方永久居住，”格里菲斯大学澳大利亚人类进化研究中心考古学教授亚当·布鲁姆在一封电子邮件中写道。

在所谓的“新石器时代革命”期间，如今以色列境内的农民首次用大麦酿造啤酒。此前的证据表明，早在4000年前，东南亚地区就出现了嚼槟榔的现象。

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但布鲁姆的团队发现证据表明，史前采集者在25000至16000年前就开始吮吸整颗槟榔。这种做法可能代表了人类已知最早的药物使用案例，并最终演变成如今仍然非常流行的嚼槟榔习惯。

布鲁姆是周三发表在《科学进展》杂志上的一项新研究的主要作者，他和他的同事认为，虽然槟榔的效力不如嚼槟榔，但整颗槟榔也能起到止痛作用——但这会产生连锁反应，只会导致更多的疼痛。

布鲁姆说：“苏拉威西岛的新发现表明，世界某些地区的狩猎采集社区不仅很早就开始使用植物药物，而且他们还开始依赖植物的神经活性，并遭受长期使用带来的负面后果。”

2017 年，布鲁姆的团队在南苏拉威西省马罗斯-庞克普喀斯特山区的石灰岩洞穴 Leang Bulu Bettue 中发现了一组遗骸。

这块上颌骨碎片属于一位成年人，经鉴定是一位生活在25000至16000年前的农业出现之前的采集者。布鲁姆说，其中三颗牙齿仍然保存完好，而且令人惊讶的是，其中两颗牙齿上有很深的圆形沟槽。

史前遗骸在苏拉威西岛等热带环境中不易保存，因此下颌骨的发现十分罕见。

另一支研究团队在距离此处约 33 公里（20.5 英里）的另一个洞穴遗址——梁卡波隆博洞穴（Leang Cappolombo）——发现了另一名成年觅食者的遗骸，其牙齿上也留有同样的特征性凹槽，但年代可追溯至 7600 至 6300 年前。这一发现同样是在 2017 年，但布鲁姆的团队直到三年前才有机会对这些牙齿进行研究。

研究人员表示，两人去世时至少都已35岁，甚至可能更大。

研究人员发现，这些觅食者牙齿上的磨损痕迹与之前发现的嚼槟榔痕迹并不相符。相反，这些沟槽很可能是由于他们习惯性地吮吸坚硬的圆形物体（例如完整的槟榔）造成的。

研究团队还分析了牙齿组织，并检测到了槟榔碱的痕迹，槟榔碱是槟榔中主要的止痛化合物。

布鲁姆说：“这些采集者的牙齿健康状况很差，所以吮吸坚果很可能是他们治疗牙痛的传统方法。然而，这些坚硬的圆形种子具有磨蚀性。长期频繁地吮吸坚果会逐渐严重磨损牙齿，最终导致牙齿内部敏感的牙髓腔，也就是牙齿的‘活体核心’暴露出来。”

布鲁姆补充说，暴露的牙髓腔会引起剧烈的疼痛，导致进食困难，并可能引发感染扩散到牙根甚至颌骨。

布鲁姆说：“我们怀疑这些人已经病态地沉迷于嚼槟榔，以此来缓解这种文化习俗带来的口腔疼痛。实际上，他们陷入了一个恶性循环。”

由于没有强效的熟石灰来激活坚果的精神活性作用，布鲁姆和他的团队质疑，这些觅食者可能会经历怎样的精神改变效果。

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研究团队将槟榔浸泡在人工合成的唾液中——这种唾液是由盐溶液和有助于分解食物的酶混合而成——以进行生化分析。科学家们用这些“溶液”测试了嵌入蛙卵细胞中的克隆人类受体（包括调节神经活动的蛋白质）。

布鲁姆说：“这表明，即使只是吮吸完整的槟榔，也会释放出足够多的槟榔碱，从而产生生理效应，改变大脑功能。”

研究作者表示，嚼槟榔是一种由来已久的文化习俗，其根源可以追溯到数千年前的狩猎采集传统。

“新数据将嚼槟榔置于一个截然不同的社会背景中，”爱达荷州博伊西州立大学助理临床教授、古植物民族学专家马里奥·齐默尔曼博士在电子邮件中写道。古植物民族学依靠古代植物遗存来识别人们如何利用不同的植物。齐默尔曼博士并未参与这项新研究，但他在编辑过程中担任了同行评审员。

“我们团队去年的研究结果表明，青铜时代等级森严的社会中就已开始使用这种武器，”齐默尔曼说。

但他补充说，这项新研究提供了证据，表明平等的人之间有习惯性地使用槟榔的现象。

研究作者推测，这种习俗可能在 4000 年前演变为嚼槟榔，当时被称为南岛语族的早期新石器时代定居者随着农业社会从台湾向苏拉威西岛扩张而定居。

森本直树/KyotoU

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布鲁姆说：“我们认为，南岛语系农民看到苏拉威西岛的原住民嚼槟榔，便将这种习惯据为己有，并在此基础上进行了创新：将槟榔与熟石灰一起咀嚼。值得注意的是，这些早期农民还用这种物质制作陶器。”

布鲁姆尝试吮吸槟榔，体验史前觅食者的感受，他称这种体验“非常不愉快”，因为在吮吸过程中会释放出涩味液体。

然而，他的嘴里确实出现了麻木感，这本可以暂时缓解觅食者的牙痛——尽管这会损害他们的牙齿健康。

齐默尔曼表示，这项研究有助于凸显摄入非膳食物质长期以来一直是人类经验的一部分。

“我们摄取食物不仅仅是为了解渴解饿，”齐默尔曼说。“数万年来，人类食用动植物产品的目的包括缓解疼痛、增强耐力、促进社交互动或沉浸于另一种现实之中。”

现在，布鲁姆想要探究其他常见物质滥用习惯究竟可以追溯到多久以前。

布鲁姆说：“饮用发酵水果致醉并非人类独有——鸟类也会这样做。我怀疑，早在大约13000年前新石器时代农业出现之前，世界各地的采集者就已经开始制作和饮用发酵饮料了。”