NEWSFOCUS on February 3, 2014 www.sciencemag.org The Dangerous Professor Downloaded from David Nutt wants to make policies science-based and give the world a safe alternative to alcohol. If only politicians would listen, he says

LONDON—David Nutt is trying to develop develop further. “We know people like alco- scientifi cally unfeasible. a new recreational drug that he hopes will hol, they like the relaxation, they like the Nutt wasn’t surprised. As a fi erce advo- be taken up by millions of people around sense of inebriation,” Nutt says. “Why don’t cate of what he says are more enlightened, the world. No, the 62-year-old scientist isn’t we just allow them to do it with a drug that rational drug policies, he has been a light- “breaking bad.” In fact, he hopes to do good. isn’t going to rot their liver or their heart?” ning rod for a long time. Politicians, in His drug would be a substitute for alcohol, to But when he presented the idea on a Nutt’s view, make irrational decisions about create drinks that are just as intoxicating as BBC radio program late last year and made that help them win votes but cost beer or whiskey but less toxic. And it would an appeal for funding, many were appalled. society dearly. is often based on come with an antidote to reverse its effects, A charity working on alcohol issues criti- the moral judgment that people should not allowing people to sober up instantly and cized him for “swapping potentially one use drugs, he says. Instead, it should refl ect drive home safely. addictive substance for another”; a com- what science knows about the harms of dif- Nutt, a neuropsychopharmacologist at mentator called the broadcast “outrageous.” ferent drugs—notably that many are far and a former top News-papers likened his synthetic drug to less harmful than legal substances such as adviser to the British government on drug soma, the intoxicating compound in Aldous alcohol, he says. The plan for a synthetic policy, says he has already identified a Huxley’s dystopian novel Brave New World. alcohol alternative is his own attempt to

couple of candidates, which he is eager to Some of his colleagues dismissed the idea as reduce the damage that drug use can wreak; THOMPSON IMPERIAL COLLEGE LONDON/LAYTON CREDIT:

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Outspoken. Nutt says politicians often have a “primi- Clinical Science at the U.S. National Institute “Because one’s illegal.” tive, childish” way of thinking about drugs. on Alcohol Abuse and Alcoholism, a job he “Why is it illegal?” held for 2 years. Today, he runs the department “Because it’s harmful.” he believes it could save millions of lives and of at Imperial “Don’t we need to compare harms to billions of dollars. College, using modern imaging techniques determine if it should be illegal?” Such views—and the combative way in to see what happens in the when people “You can’t compare harms from a legal which he espouses them—frequently land take drugs or develop an addiction. activity with an illegal one.” Nutt in fierce disputes. Newspaper com- But his biggest contribution to science, Nutt says this kind of circular logic crops mentators have called him “Professor Nutty” he says, was a discovery he made quite early up again and again when he discusses recre- or “the dangerous professor.” In 2009, he in his career: that some molecules don’t just ational drugs with politicians. “It’s what we was sacked from his position as chair of the block receptors in the brain, but actually have would call ‘splitting’ in psychiatric terms: United Kingdom’s Advisory Council on the the opposite effect of the molecules that nor- this primitive, childish way of thinking Misuse of Drugs, tasked with giving scien- mally stimulate them—and in doing so shut things are either good or bad,” he says. tifi c advice to the home secretary, after he down a brain pathway. Nutt called these mol- He’s often that outspoken. He likens the criticized a government decision on . ecules contragonists, and he has made a sec- way drug laws are hampering legitimate sci- But in November 2013, he received the ond career out of being a bit of a contragonist entific research, for instance into medical John Maddox Prize for standing up for sci- himself, trying to calm society’s overexcited applications for psychedelic compounds, ence. “In circumstances that would have responses to the steady stream of alarming to the church’s actions against Galileo and humiliated and silenced most people,” news about drugs. Copernicus. When the United Kingdom wrote neurobiologist , recently banned khat, a plant containing a one of the judges, “David Nutt continued to Fictional affl iction that’s popular among people from affi rm the importance of evidence in under- In 2009, Nutt published an article in the the Horn of Africa and the Arabian Penin- standing the harms of drugs and in develop- Journal of Psychopharmacology comparing sula, he compared the decision with banning ing drug policy.” the harms from ecstasy with those caused by cats. And he accuses the Russian govern- horse riding. Every 10,000th ecstasy pill is ment of deliberately using alcohol to weaken Controversial comparisons likely to hurt someone, he calculated, while the opposition. “However miserable they are, David Nutt does not look like a danger- ous professor. Short and heavyset, he has a jovial, round face and an old-fashioned mus- tache; one could mistake him for a London “You don’t get to be on the front page of and taxi driver. He limps slightly, has a down-to- The New York Times unless you sharpen your arguments a earth way of speaking, and laughs a lot when little bit. I can live with that.” he talks. “He is a real personality,” says —Jürgen Rehm psychopharmacologist Rainer Spanagel of Heidelberg University in Germany. “You can be in a meeting and almost have a result, “[ Nutt] is a polarizing fi gure and the drug policy area is then he will come in an hour late, stir every- thing up, and in the end convince everyone polarized enough.” —Jonathan Caulkins of his position.” Nutt says he realized at an early age that “understanding how the brain works is the most interesting and challenging question an average horse enthusiast can expect a seri- however much they hate their government and in the universe.” When he was a teenager, ous accident every 350 hours of riding. The their country, they will just drink until they kill his father told him a story of how Albert sport, he concluded, was more dangerous themselves, so they won’t protest,” he says. Hofmann, the discoverer of LSD, took a dose than the notorious party drug. That “raises But it’s his stance on cannabis that got him of that drug and felt that the bike ride home the critical question of why society tolerates sacked. In early 2009, ignoring advice from took hours instead of minutes. “Isn’t that —indeed encourages—certain forms of Nutt’s advisory council, Smith upgraded can- incredible, that a drug can change time?” he potentially harmful behaviour but not others nabis from class C to class B, increasing the asks. On his fi rst night as an undergraduate in such as drug use,” he added. maximum penalty for possession from 2 to Cambridge, he witnessed the powers of drugs Politicians were not amused, and Nutt’s 5 years in prison. A few months later, Nutt again when he went drinking with fellow whimsical reference to a fictional afflic- criticized the decision in a public lecture, students. Two of them couldn’t stop. “I just tion he called equine addiction syndrome, arguing that “overall, cannabis use does watched them transform themselves. One of or “equasy,” did not help. In his book not lead to major health problems” and that them started wailing and crying and the other Drugs - Without the Hot Air, Nutt provided tobacco and alcohol were more harmful. became incredibly hostile.” his account of a phone conversation he had When media reported the remarks, Alan During his clinical training, Nutt says he with U.K. Home Secretary Johnson, who succeeded Smith as home sec- treated many alcoholics but failed “to get any- after the paper was published. (Smith calls it retary in mid-2009, asked him to resign. “He one interested in how to reduce their addiction an “embroidered version” of their talk.) was asked to go because he cannot be both a to the drug that was harming them.” He set Smith: “You can’t compare harms from a government adviser and a campaigner against out to answer that question, fi rst in the United legal activity with an illegal one.” government policy,” Johnson wrote in a letter Kingdom, later as the chief of the Section of Nutt: “Why not?” in .

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Nutt did not go quietly. With financial sharpen your arguments a little bit,” Rehm they may be, would constitute a quantum help from a young hedge fund manager, says. “I can live with that.” leap of progress towards evidence-based and Toby Jackson, he set up a rival body, the more rational drug policy in Canada and else- Independent Scientifi c Committee on Drugs, Ranking the drugs where,” two Canadian drug scientists wrote “to ensure that the public can access clear, In 2010, Nutt sparked a new fi restorm when in Addiction. Regardless of its quality, the evidence based information on drugs with- he published another comparison: a Lancet paper has been hugely influential, Rehm out interference from political or commer- paper ranking drugs according to the harm says. “Everyone in the E.U. knows that paper, cial interest.” Politics have skewed not just they cause. Nutt and other experts scored a whether they like it or not. There is a time drug laws but research itself, he argues. “If long list of drugs on 16 criteria, nine related before that paper and a time after it appeared.” you want to get money from the U.S. govern- to the user, such as death from an overdose Nutt says his comparisons are an essential ment to work on a drug, you have to prove it or wrecked relationships, and seven related fi rst step on the way to more evidence-based damages the brain,” he says. to society, such as drug-fueled violence and drug policies that seek to reduce harm rather One of his favorite examples is a paper economic costs. In the end, every drug was than to moralize. The best option would be that Science published in September 2002. given a score between 0 and 100 to indicate a regulated market for alcohol and all sub- The study, led by George Ricaurte at Johns its overall harm. Alcohol came out on top, stances less harmful to the user than alcohol, Hopkins University, seemed to show that ahead of ; mushrooms and ecstasy he argues. monkeys given just two or three doses of were at the low end (see graphic, p. 481). That scenario, under which only heroin, ecstasy, chemically known as MDMA, Critics said the study’s methodology was crack , and would developed severe brain damage. The fi nd- fl awed because it didn’t address drug interac- remain illegal, seems unlikely to become a ing suggested that “even individuals who use tions and the social context of drug use. “For reality. But Nutt says he can already see more MDMA on one occasion may be at risk for instance, the number of fatalities caused by rational policies taking hold. Recently, Uru- guay and the U.S. states of Colorado and Washington legalized the sale of recreational cannabis, going a step further than the Neth- “ We know people like alcohol, they like the relaxation, they like erlands, which stopped enforcing laws on the the sense of inebriation. Why don’t we just allow them to do it sale and possession of small amounts of soft with a drug that isn’t going to rot their liver or their heart?” drugs decades ago. Nutt was also happy to read President Barack Obama’s recent com- —David Nutt ment that cannabis is less harmful than alco- hol. “At last, a politician telling the truth,” he “ You could come up with a drug that might make you feel says. “I’ll warn him though—I was sacked for saying that.” good. But is it going to be the same good feeling as alcohol? New Zealand, meanwhile, passed a law in I doubt that.” 2013 that paves the way for newly invented —Gregg Homanics recreational drugs to be sold legally if they have a “low risk” of harming the user. Nutt, who has advised the New Zealand govern- substantial brain injury,” the authors wrote. excessive alcohol use is going to depend in ment, is delighted by what he calls a “ratio- The paper received massive media atten- part on gun control laws,” says Caulkins, nal revolution in dealing with recreational tion, but it was retracted a year later after the who calls the whole idea of expressing drug drugs.” The main problem now, he says, is authors discovered that they had accidentally harm as a single number “embarrassing.” establishing new drugs’ risks—which is dif- injected the animals not with MDMA but Caulkins adds that even if a perfect rank- fi cult because New Zealand does not allow with methamphetamine, also known as crys- ing of drug harms were possible, it wouldn’t them to be tested on animals—and deciding tal meth, which was already known to have mean that politicians should put the tight- what “low risk” actually means. “I told them the effects seen in the monkeys. Nutt says the est control measures on the most harmful the threshold should be if it is safer than alco- mistake should have been obvious from the drugs. Suppose drug A is more harmful to hol,” he says. “They said: ‘Oh my god, that is start because the data were “clearly wrong” the individual and society than drug B, he going to be far too dangerous.’ ” and “scientifically implausible.” “If that says, but impurities in drug A, when illegally result was true, then kids would have been produced, can lead to potentially fatal organ Safer substitute dropping dead from Parkinson’s,” he says. failure while they just taste bad in drug B. If Nutt agrees that alcohol is now one of the Some resent this combative style. “He is a you were going to prohibit only one of the most dangerous drugs on the market—which polarizing fi gure and the drug policy area is two drugs, it should be drug B, he says, even is why he’s trying to invent a safer substitute. polarized enough,” says Jonathan Caulkins, though it causes less harm per se, because The World Health Organization estimates that a professor of public policy at Carnegie Mel- criminalizing drug A would lead to a more alcohol—whose harms range from liver cir- lon University in Pittsburgh, Pennsylvania. dangerous product and more deaths. Nutt’s rhosis, cancer, and fetal alcohol syndrome to But Jürgen Rehm, an epidemiologist at the ranking of drugs, he says, is “a pseudoscien- drunk driving and domestic violence—kills Centre for Addiction and Mental Health in tifi c exercise which is trying to take control about 2.5 million people annually. “When I Toronto, Canada, says Nutt has helped stim- of the policy process from a technocratic per- scan the of people with chronic alco- ulate debates that were long overdue. “You spective in a way that isn’t even sound.” hol dependence, many have brains which don’t get to be on the front page of The Other scientists defended the paper. Using are more damaged than those of people with Lancet and The New York Times unless you Nutt’s harm scales, “fl awed and limited as Alzheimer’s,” Nutt says.

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In a paper published this month in the was pleasantly surprised. “After exploring drug candidates precisely because they had Journal of Psychopharmacology, Nutt and one possible compound I was quite relaxed side effects similar to alcohol intoxication. Rehm summarize the top six interventions and sleepily inebriated for an hour or so, Gregg Homanics, an alcohol researcher that governments should consider to reduce then within minutes of taking the antidote I at the University of Pittsburgh, is skepti- the harms of alcohol, such as minimum was up giving a lecture with no impairment cal that another substance could mimic all prices and restrictions on the places that can whatsoever,” he wrote in a recent article. the positive effects of alcohol. “You could sell hard liquor. They also argue that gov- But he wants to go one step further. “We come up with a drug that might make you ernments should support the development know that different subtypes of GABA feel good. But is it going to be the same good of alternatives. Nutt points to e-cigarettes— mimic different effects of alcohol,” he says. feeling as alcohol? I doubt that.” Such a drug devices that heat and vapor- might have downsides of its ize a nicotine solution—as a Harm Caused by Drugs own, warns Andreas Heinz, model. “In theory, electronic an addiction researcher at cigarettes could save 5 mil- Harm to others Harm to users Charité University Medicine lion lives a year. That is more Alcohol Berlin. It could still turn out than [the death toll from] to be addictive or to harm a AIDS, malaria, tuberculosis, Heroin small proportion of the pop- and meningitis put together,” ulation. “There is an advan- Crack cocaine he says. “I would argue that tage when you have known the e-cigarette is going to be Methamphetamine drugs for hundreds of years the greatest health invention and you know exactly what since vaccination.” Cocaine they do,” he says. Can an alcohol alterna- Tobacco Still, Nutt’s appearance tive do the same? “I think on the BBC radio program that idea is utopian,” says Amphetamine attracted new investors, Spanagel, the German psy- ranging “from Ukrainian Cannabis chopharmacologist. One rea- brewers to American hedge son is that researchers have GHB funds,” he says, and Imperial recently developed a much Innovations, a company that more complex picture of what Benzodiazepines provides technology trans- ethanol, as chemists call it, Ketamine fer services, is working with actually does. Twenty years him “to consider a range ago, they thought that once Methadone of options for taking the it reached the brain, alcohol research forward,” a spokes- elicited its many effects by person says. “We think we infiltrating the membranes Butane have enough funding now to of neurons there and chang- take a substance all the way ing their properties. “Now Khat to the market,” Nutt says— we know that’s nonsense. You Anabolic steroids in fact, he hopes to be able would have to drink 5 liters of to offer the first cocktails schnapps for that to happen,” Ecstasy for sale in as little as a year Spanagel says. from now. LSD In fact, scientists have Even a very good alcohol learned that alcohol, like Buprenorphine substitute would face obsta- other drugs, interacts with the cles. Many people won’t receptors for certain neuro- Mushrooms forsake drinks they have transmitters. But unlike other 100 80 60 40 20 0 0 20 40 60 80 100 long known and loved— drugs, it acts on a wide range such as beer, wine, and of them, including receptors Scoring drugs. Nutt and colleagues at Scientifi c Committee on Drugs in whiskey—for a new chemi- for GABA, NMDA, sero- London ranked 20 drugs according to how harmful they are to the individual user and to cal, Spanagel says. The idea tonin, and acetylcholine. That others, expressed as a number between 0 and 100. They deemed crack cocaine the most will also trigger all kinds will make it hard to find a harmful drug to the user and alcohol most harmful to U.K. society. of political and regulatory substance to emulate most of debates, Rehm says. “How alcohol’s wanted effects while avoiding the Nutt combed the scientifi c literature and pat- will such a new drug be seen? Will you be unwanted ones, Spanagel predicts. ents for compounds targeting specifi c GABA able to buy it in the supermarket? In the Nutt is concentrating on the GABA receptors, and, in an as-yet unpublished pharmacy? Will society accept it?” system—the most important inhibitory sys- report that he shared with Science, he iden- Whatever the outcome, Nutt’s quest for tem in mammalian brains. Alcohol activates tifi es several molecules that he says fi t the a safer drink has already made people think GABA receptors, effectively quieting the bill. Compounds targeting subtypes of the about alcohol in a new way, Rehm adds. “It’s brain and leading to the state of relaxation GABAA receptor called alpha2 and alpha3 provocative in the best sense of the word.” many people seek. Nutt has sampled some are particularly promising, he says. Some of Much the same could be said of the scientist

GRAPH SOURCE: DAVID NUTT GRAPHSOURCE: DAVID compounds that target GABA receptors and these molecules were dropped as therapeutic who thought it up. –KAI KUPFERSCHMIDT

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