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.

A silent liver-destroying virus continues to spread across the United States at an accelerating pace, even though the drugs that cure it have been on pharmacy shelves for nearly a decade. In a perspective article published in the Journal of General Internal Medicine, two University of California, Los Angeles physicians argue that the nation’s faltering response to hepatitis C could be rescued by borrowing the playbook that transformed the HIV epidemic, from community-based testing and rapid “test and treat” initiation to federally funded safety nets and a fundamental reframing of what treatment nonadherence actually means.

The paper, written by Dr. Anna C. Scialli of UCLA’s Division of General Internal Medicine and Dr. Tara Vijayan of the Division of Infectious Diseases, opens with a clinical vignette that captures the paradox of modern hepatitis C care. A 34-year-old man with a history of injection drug use and unstable housing arrived at a hospital with fever, fatigue, and shortness of breath, and was found to have Staphylococcus aureus endocarditis with septic emboli. Screening revealed chronic hepatitis C virus infection. He was eager to begin treatment, and during a 39-day admission that included respiratory failure management and tricuspid valve replacement, clinicians started him on glecaprevir-pibrentasvir, obtained through the institution’s specialty pharmacy because the drug was not on the hospital formulary. It is precisely this kind of opportunistic, in-hospital treatment that the authors want to make routine.

The numbers they cite are stark. Between 2015 and 2022, the United States saw an estimated twofold increase in acute hepatitis C infections, yet only about a third of insured individuals diagnosed with the virus receive treatment within a year of diagnosis. Up to four million Americans are believed to carry the virus. By contrast, in HIV care, where the “care cascade” framework originally took root, roughly 76 percent of people diagnosed with HIV receive care and 65 percent are virally suppressed. The cascade framework, which tracks patients through sequential steps of diagnosis, linkage to care, receipt of direct-acting antivirals, and achievement of sustained virologic response, has been adopted by hepatitis C elimination strategies, but outcomes at every step have persistently lagged behind HIV milestones.

On the surface, the two viruses could hardly be more different biologically. Untreated HIV progressively depletes CD4 lymphocyte counts, producing the opportunistic infections and malignancies that define AIDS, a disease that is fatal within years for all but a rare fraction, less than half a percent, of “long-term non-progressors.” Chronic hepatitis C, meanwhile, may smolder asymptomatically for decades, gradually driving liver inflammation and fibrosis, with an estimated 5 to 10 percent of patients developing cirrhosis after twenty years and a 1 to 3 percent cumulative rate of hepatocellular carcinoma after thirty years. But the authors emphasize that the two epidemics share a critical social anatomy: both concentrate in the most marginalized communities, among people with limited access to prevention and treatment and distinct socioeconomic disparities. Their public health histories, they argue, overlap enough to yield forty years of transferable lessons.

The parallels run deep from the very beginning. HIV was first observed in New York as early as 1978 but was not formally reported until 1981, when Los Angeles physicians described Pneumocystis pneumonia in five men who have sex with men in the CDC’s Morbidity and Mortality Weekly Report. By 1990, more than 100,000 Americans had died of AIDS, and the disease, pejoratively labeled a “gay cancer,” became a vehicle for stigma and the marginalization of sexual minorities. Hepatitis C followed an eerily similar timeline. First described in 1975 as “non-A, non-B hepatitis” among transfusion recipients, accounting for up to 90 percent of transfusion-associated hepatitis, it was not definitively identified until 1989, when researchers isolated HCV RNA and developed an antibody test. Widespread blood-supply screening followed by 1992, and screening recommendations evolved from risk-based targeting to universal one-time screening of all adults by 2020, as rising infection rates among younger people shifted the epidemic’s demographics.

Treatment histories also rhyme. HIV therapy evolved from poorly tolerated early regimens to the 1996 introduction of combination antiretroviral therapy, then single-tablet regimens in the 2000s that improved adherence and reduced toxicity, and most recently long-acting injectables such as cabotegravir and rilpivirine, which maintain viral suppression with dramatically reduced adherence barriers. Hepatitis C treatment traveled its own arc, from interferon-alpha with cure rates low enough and durations long enough, up to 72 weeks, to be nearly prohibitive, through pegylated interferon plus ribavirin combinations marked by flu-like symptoms, depression, and hemolytic anemia, to the revolutionary direct-acting antivirals of the 2010s. The pan-genotypic regimens first approved by the FDA in 2016, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, now offer eight-to-twelve-week, once-daily courses with rare side effects, no laboratory monitoring, and cure in over 95 percent of those treated. Because the cure is short, simple, and complete, the authors note, the technical barriers to hepatitis C eradication should be far lower than for HIV. That they are not is the central problem.

The first lesson concerns testing. Only an estimated 55 percent of people with hepatitis C are aware of their diagnosis, compared with an estimated 87 percent of people living with HIV. In the HIV epidemic, the shift from risk-based testing toward universal opt-out screening, launched by the CDC in 2006 when 21 percent of infections were undiagnosed, helped reduce undiagnosed infections to 15 percent by 2015. Crucially, that progress was driven by low-barrier testing outside traditional health facilities: mobile clinics, emergency rooms, community health fairs, and inpatient units. For hepatitis C, the settings with the highest testing yields today are syringe service programs and clinics treating substance use disorder, but the authors insist these cannot be the only option, particularly since syringe service programs lack federal support. They advocate a broad test-and-treat strategy, including initiating direct-acting antivirals during hospital admission. Because most hospitals will not stock the drugs, they propose a practical mechanism: prescribing through a contracted specialty pharmacy that purchases medications at 340B pricing and delivers them to the bedside, stored securely on the ward much like an unavailable home medication.

The second lesson concerns insurance and funding. Many state Medicaid programs still impose sobriety requirements and fibrosis-stage restrictions on hepatitis C treatment, and states with such restrictions treat fewer patients, despite explicit recommendations from the Infectious Diseases Society of America and the American Association for the Study of Liver Diseases to remove them. Private insurers are even less transparent, denying more than half of hepatitis C treatment claims in one national specialty pharmacy cohort study. HIV care took a different path: the Ryan White CARE Act of 1990 created a federally funded safety net covering antiretroviral therapy for uninsured and underinsured patients, now supporting 82 percent of uninsured people living with HIV. Early hospital initiation of antiretroviral therapy has been shown to improve linkage to care, especially for patients with substance use disorder. No equivalent exists for hepatitis C, even though an estimated 60 percent of people with the virus are covered by public insurance, and the 2025 One Big Beautiful Bill cut nearly one trillion dollars from Medicaid over the coming decade. Meanwhile, budget pressures threaten HIV’s own safety net: as of February 2026, twenty states were tightening AIDS Drug Assistance Program eligibility, and models estimate up to a 73 percent increase in new HIV infections across thirty states if that funding disappears.

The third lesson is the most philosophical. Provider hesitancy, particularly toward people who use drugs, remains a powerful barrier to hepatitis C treatment, with physicians frequently citing concerns about nonadherence. Yet studies show people who use drugs complete hepatitis C treatment more than 96 percent of the time. HIV advocacy movements, notably ACT UP, forced a reframing: nonadherence was reinterpreted not as a moral failing of the patient but as a failure of systems in which marginalized groups face enormous barriers. Current CDC guidelines now explicitly state that homelessness, substance use, and mental health conditions are not justifiable reasons to defer antiretroviral therapy, and federally funded supports, from Ryan White case management and patient navigation to the Housing Opportunities for Persons with AIDS program, address the social determinants that undermine adherence. Peer navigation programs and drug user unions are emerging as hepatitis C analogs, but without matching federal investment.

The Norway-based OPPORTUNI-C trial provides the empirical anchor for the authors’ central proposal: among people who inject drugs, 68 percent of those who began hepatitis C treatment while hospitalized completed it, compared with just 35 percent of those referred to outpatient care. For a population with frequent admissions and siloed inpatient care, the hospital bedside may be the single best opportunity to deliver a cure. As antiretroviral therapy became simpler and its community-level benefits clear, the authors write, reducing time to treatment initiation became not merely a public health measure but a moral imperative. With a twelve-week cure available, they argue, hepatitis C elimination now depends on treating patients where they are.