Feature THE SCIENTIST BATTLING THE ADDICTION CRISIS Nora Volkow leads the world’s biggest funder of addiction research, and now she’s facing her greatest test in the opioid crisis. By Emiliano Rodríguez Mega n a cold Friday night in February 1995, for another few days and was sent home with comeback of cocaine and methamphetamine, addiction researcher Nora Volkow more. But she decided not to take it. She was and a two-decade-old opioid epidemic that has and her husband got into their car afraid — she knew many of her patients could devastated many parts of the country: opioid after a long day at Brookhaven not stop once they started. She would get overdoses have killed nearly half a million peo- National Laboratory in Upton, New through the pain without the help of drugs. ple in the United States (see ‘Tackling the opioid York. Ice had covered the trees and That night, a discomfort she had never felt epidemic’). In response, her agency has started the roads, making them sparkle. But before overran her body. She felt restless, projects to monitor drug use and has ploughed as the couple drove down a slope, agitated, desperate. Volkow took a painkiller money into medications that can reduce the Othe tyres lost their grip. The vehicle spun out and, like an apparition, the feeling faded away. cravings and pleasurable effects of drugs. of control. Volkow curled up to shield herself as “It was then that I realized how fast depend- Critics have long argued that Volkow’s an oncoming car crashed into her door. ence develops,” she says. “It also made me emphasis on the brain minimizes the roles Metal bit into her flesh. The pain was realize that I’m very afraid of opiates.” that social and economic forces have in mak- unrelenting. Finally, the fire service arrived Twenty-five years later, Volkow’s name has ing people prone to addiction. In the past year, to break her free and an ambulance rushed her become widely known in the addiction field and Volkow has begun to acknowledge that factors to the nearest emergency department, where beyond. As a neuroscientist who has directed such as homelessness, unemployment and a doctor gave her Demerol, a powerful and the US National Institute on Drug Abuse (NIDA) isolation can make people more vulnerable highly addictive opioid painkiller also known in Rockville, Maryland, since 2003, she has to drugs and less likely to recover. But some as pethidine, which is similar to morphine. championed the idea of addiction as a disease researchers contend that the agency’s funding Volkow had spent countless hours talking to of the brain rather than a moral failing. Under decisions have been slow to reflect this shift people with addiction and had read hundreds her direction, NIDA has prioritized research on in mindset. They say that NIDA’s focus on the of papers on the mechanisms of drug abuse. the biological basis of addiction, and fought brain is disproportionate, and they worry Neither prepared her for what happened next. against the mistreatment of drug abusers in about its outsized power over policies tack- “It was extraordinary, those impressive both the medical and criminal-justice systems. ling drug use and addiction. “NIDA’s influence sensations,” she says. A moment of ecstasy, Her quest has taken on a new urgency as is significant; people follow that lead,” says one she describes as comparable only to the United States finds itself contending with Ingrid Walker, a cultural-studies researcher long-lasting sexual pleasure, eclipsed all shifts in the legal status of cannabis, a grow- at the University of Washington in Tacoma. other feelings. She stayed on the medication ing market for electronic cigarettes, a sudden Nonetheless, Volkow’s obsession with 178 | Nature | Vol 580 | 9 April 2020 ©2020 Spri nger Nature Li mited. All ri ghts reserved. ©2020 Spri nger Nature Li mited. All ri ghts reserved. says Brodie. “Her enthusiasm was boundless.” Volkow soon became involved in every project, from looking for brain-tumour biomarkers1 to detecting differences in brain activity between people with and without schizophrenia2. Her reputation as a rebellious yet brilliant scientist began to take shape. “Nora was certain that she was always right, and sometimes she was,” says Brodie. “Perhaps, even, most of the time.” Scanning for insights By the mid-1980s, Volkow had completed a psychiatry residency at NYU and moved to the University of Texas Health Science Center in Houston to work in its imaging facility. She intended to study schizophrenia, but the cocaine craze was bringing with it a surge of addicted people. In PET scan after PET scan, Volkow spotted anomalies in these individuals’ brains. “You’d see holes, gaps where blood flow should be,” she says. She suggested that cocaine chokes blood vessels to the extent that they don’t allow proper circulation3 — similar to small strokes. Her findings contradicted the belief, common at the time, that cocaine was a relatively safe substance — although the 1986 deaths of two celebrated US sportsmen (basketball player Len Bias and American football player Don Rogers) changed that perception. In 1987, Volkow moved to Brookhaven National Laboratory, where for the next 16 years she continued to probe the effects of drugs on the brain. She used radioisotopes to label cocaine, tracking how rapidly it triggers the neurotransmitter dopamine in the brain Nora Volkow at her childhood home in Mexico City. and how quickly it dissipates, and arguing that the speed of its effect could explain why the understanding the biological effects of do with science, the answer was ‘yes’,” she says. drug is so powerfully addictive. NATURE excessive drug use — fuelled in part by her own She once asked him if she could bring home a While at Brookhaven, Volkow kept question- family’s past — has not only shattered dogmas corpse and dissect it. He approved; Volkow’s ing long-held assumptions in neuroscience. in neuroscience; it has also helped to mitigate mother and sisters threatened to leave the The general agreement was that addictive the stigma faced by those living with addiction. house. But she did end up with some bones to substances impaired the brain’s reward “Her mission in life was to harvest the power examine. “When something interests me,” she centres, tempting people to keep trying the ALEJANDRA RAJAL FOR FOR RAJAL ALEJANDRA of science to change lives of millions of peo- says, “I won’t quit until I understand it.” substances to feel good. But that didn’t explain ple,” says Bertha Madras, a psychobiologist That same curiosity and stubbornness why so many patients had told her that they felt at Harvard Medical School who is based at would guide most of her career. After graduat- compelled to take the drugs, even when they McLean Hospital in Belmont, Massachusetts. ing top of her class, she was accepted to study had long lost that pleasure. It was as if they had “And she has done that.” psychology at the Massachusetts Institute of lost the power to decide. This more-complex Technology in Cambridge. But a 1980 article in reaction seemed to implicate more than just Revolutionary heritage Scientific American disrupted her plans. the brain areas that process reward. Volkow grew up in Mexico City, one of four The piece described how a new technol- A series of key discoveries came in the 1990s. daughters of Soviet and Spanish immigrants. ogy, positron emission tomography (PET), Volkow noticed that the prefrontal cortex, the Their mother, an haute-couture dressmaker was allowing neuroimagers to look into brain region that regulates decision-making from Madrid, sought refuge in Mexico to escape living brains and watch their activity patterns. and self-control, was underactive in men who Francisco Franco’s dictatorship. Their father, Volkow was instantly hooked. were addicted to cocaine — an anomaly that a chemist, was also a refugee. He had come to Soon after reading the article, she secured a might sometimes precede addiction, making Mexico City as a 13-year-old in 1939 to live with research job in the lab of psychiatrist Jonathan a person more vulnerable to it. Dysfunction his only surviving relative — his grandfather, the Brodie at what was then New York University in decision-making regions, she suggested, exiled Soviet revolutionary leader Leon Trotsky. (NYU) Medical Center in New York City, which was why drug-addicted people felt they had As a teenager, Volkow was captivated by had a vibrant programme using the technol- lost control. Furthermore, she and her team the human brain and studied medicine at the ogy for neuroimaging. Brodie was starting to found, repeated cocaine use desensitized the National Autonomous University of Mexico in do PET scans with the aim of studying various brain by killing off dopamine receptors, which Mexico City. Her father encouraged her with- brain disorders in people. diminished the reward people felt from the out limits. “Whatever I asked my dad that had to “Clearly, she was a star from the beginning,” drug even as it increased their dependence on Nature | Vol 580 | 9 April 2020 | 179 ©2020 Spri nger Nature Li mited. All ri ghts reserved. ©2020 Spri nger Nature Li mited. All ri ghts reserved. Feature it4. Volkow and her colleagues later replicated until it changed its policy in 2018, the FDA — absorbing the history of Volkow’s family. these results in people who had misused had approved such treatments only if they Volkow has come back to Mexico City to visit alcohol, heroin or methamphetamine. could show that they fostered abstinence7. relatives, as she does almost every year. She The blobby PET images were diagnostic And Volkow alleges (although some critics stares at the little metal door in the headstone enough for Volkow to identify which belonged disagree) that reframing addiction as a patho- that contains her great-grandfather’s urn and to addicted people and which didn’t.