When Science Goes Wrong (14 page)
In the preamble of the bill, Biden depicted rave organisers as deliberately fostering a drug culture under the hypocritical guise of concern for partygoers’ welfare. ‘Because rave promoters know that Ecstasy causes the body temperature in a user to rise and as a result causes the user to become very thirsty,’ Biden wrote, ‘many rave promoters facilitate and profit from flagrant drug use at rave parties or events by selling overpriced bottles of water and charging entrance fees to ‘chill-rooms’ where users can cool down.’ Seemingly well-meaning security measures were fraught with malevolent intent. ‘Some [rave promoters] even go so far as to hire off-duty, uniformed police officers to patrol outside of the venue to give parents the impression that the event is safe,’ according to Biden’s bill.
The RAVE Act represented a certain change of emphasis in the war against drugs. With the traditional targets – people who used or dealt in hard drugs like heroin and crack cocaine – there was little social controversy about the value of drug-control measures. With those drugs, the public perception was of random acts of violence committed by addicts in a desperate quest to finance their next fix, or by warring gang lords in disputes over their drug fiefdoms. With club drugs like Ecstasy, on the other hand, a threat to public order was much less apparent. For most users, Ecstasy is not an addictive drug – not in the traditional sense of generating an all-consuming physical dependency, at least. Because Ecstasy is generally used on an occasional basis, it doesn’t usually threaten its users with financial ruin. Nor, in most cases, does it threaten their jobs, studies, or relationships. Ecstasy use, in other words, is largely compatible with a conventional middle-class lifestyle.
Lacking a public-order platform, the advocates of strict measures against Ecstasy concentrated on the dangers that the drug might pose to its users’ health. These dangers certainly exist. Most well-recognised is the risk of acute hyperthermia – heatstroke – while under the influence of the drug. Every year, a few Ecstasy users die of hyperthermia or of hyponatraemia (overdilution of the blood caused by drinking excessive amounts of water to keep cool). Ecstasy users sometimes die in traffic accidents while under the influence of the drug, or from other drugs that are taken along with Ecstasy or that are present as adulterants in Ecstasy tablets.
Still, Ecstasy causes only a handful of acute deaths in the United States per year, and relatively few acute health problems of any kind. In the year before Senator Biden introduced the RAVE Act, fewer than two persons in 100,000 visited an emergency room with an Ecstasy-related problem, compared with 76 per 100,000 with a cocaine-related problem, according to the Drug Abuse Warning Network.
Although the acute risks are not especially great, there are some indications of long-term health hazards associated with Ecstasy use. For some users, the initial positive feelings engendered by the drug – euphoria, energy, intensified sensations, and a deep sense of intimacy with others – fade with repeated use, to be replaced by depression, memory difficulties, sleep disorders, and cognitive problems. The prevalence of these ill-effects is a topic of debate: many of the people who experience them had taken a variety of drugs, making the specific role of Ecstasy difficult to tease out. And conceivably, cause and effect are at least partly the other way around – a disposition to these mental problems might promote drug use, rather than drug use triggering the problems.
Given the nebulous nature of some of Ecstasy’s reported ill-effects, educating young people to avoid the drug has always been a challenge. One strategy has been to replace the reported psychological hazards with a very concrete physical effect – damage to the brain.
Already in 1987, the US government’s National Youth Anti-Drug Media Campaign tried this approach with a series of TV commercials that featured a chicken egg (‘This is your brain’) and the same egg frying in a pan (‘This is your brain on drugs’). For some reason, the commercials were extraordinarily memorable, even iconic – they spawned endless spin-offs, imitations and parodies. Whether they achieved their goal of reducing drug use was less clear. ‘When I saw people that were on the high school honour roll smoking pot, I realised that the commercial’s message was false,’ one young woman told CNN. ‘I remember thinking, “When are their brains going to fry?”’ By 2003, more than one billion federal dollars had been spent on this and related media campaigns, but they had no significant effect on drug use among young people, according to a US government study.
In the case of Ecstasy, the main evidence for brain damage was provided by George Ricaurte, M.D., Ph.D., a neurologist at the Johns Hopkins University School of Medicine. Ricaurte (pronounced ri-CART-ey) had made a name for himself by investigating the damaging effects of several illegal drugs on the brain, and he lost no opportunity to stress the significance of his findings to potential drug users. As such, he was a darling of the National Institute on Drug Abuse (NIDA). Along with psychiatrist Una McCann, who is his wife and collaborator, Ricaurte received nearly $16 million in funding from NIDA and other government agencies between 1989 and 2003.
In 1998 Ricaurte, McCann, and three junior colleagues had published a study that purported to show brain damage resulting from recreational use of Ecstasy. Ecstasy is a chemical derivative of amphetamine: its scientific name is 3,4 methylenedioxy-methamphetamine, or MDMA. It causes a surgelike release of the ‘feel-good’ neurotransmitter serotonin, as well as a more modest release of another transmitter, dopamine. In the 1998 study, Ricaurte’s group used a radioactive tracer, combined with positron-emission tomography (PET) scanning, to visualise the distribution of a serotonin-related molecule in the brains of persons who had used Ecstasy in the past, as well as in control subjects who had not. The resulting images showed less of the serotonin tracer in the Ecstasy users than in the controls, and some patches of brain seemed to be devoid of the tracer altogether.
Ricaurte described these results as evidence of ‘structural’ changes in the brain induced by Ecstasy use – a bit of a semantic stretch, perhaps, when referring to the distribution of a molecule. His paper did include some cautionary statements, such as an admission that the changes might not be permanent. And in fact, a German research group, who used similar techniques to study Ecstasy users at various lengths of time after their last use of the drug, has recently reported that the effects of Ecstasy ingestion on the brain’s serotonin system do at least partially reverse themselves with time.
NIDA administrators decided that they could illustrate Ricaurte’s message without harming any eggs: they printed up and distributed thousands of postcards and posters carrying images taken directly from Ricaurte’s paper. These images (which can still easily be found on the internet) juxtaposed a PET scan of the left side of the brain of a control subject with the right side of the brain of an Ecstasy user. Absurdly, most of the front of the drug user’s brain appeared to be missing, and the rest of it was riddled with large holes. By presenting PET scans as if they were actual pictures of brains, the poster heightened the paradox raised by CNN’s interviewee. Forget about honour rolls – how could a person even live and breathe with such a horrendous injury?
When I interviewed Ricaurte in 2006, I was struck by the contrast with Robert Iacono, the maverick neurosurgeon I interviewed for chapter one. Whereas Iacono was by turns humorous, pithy, and abrasive – in other words, an interviewer’s dream – Ricaurte was drily circumspect, rarely failing to discuss every possible side of a question in his desire for accuracy and fairness. When I asked him whether he thought the poster campaign was misleading, for example, he said, ‘An investigator does not play any active part in coming up with these things – the campaigns that are taken on. I don’t even know if it’s appropriate to label it a campaign. I certainly would endorse the research that generates findings that are relevant to the community or public health. I think it would be irresponsible to not make those results available to the public that pays for the research. If we’re doing research in the lab, the people who pay for that research should be privy to the results of that work. As you know, communicating results of scientific studies to the lay public is an art in itself; it’s not always easy to speak in laymen’s terms. Having said that, I think it becomes exceedingly important to make sure that the data that are being presented communicate the message in as accurate and responsible a way as possible. So the images you refer to, if what they are conveying is the impression that MDMA produces holes in people’s brains, somebody should have caught that and said, wait a minute, that is not what MDMA is doing; we think based on this research that it’s damaging serotonin neurons. And how to convey that notion appropriately with the appropriate recognitions of animal data and dosages and how much of the animal data generalises to humans – there are a number of limitations that should be recognised. If you go to the article where those images come from, we try to explain very clearly what the images are showing.’
Although Ricaurte has generally been well-regarded within the academic community, he has had his critics, especially among researchers who thought that Ecstasy might have therapeutic applications. One such person was Charles Grob, director of child and adolescent psychiatry at Harbor-UCLA Medical Center in Southern California. As he told me in a 2006 interview, Grob believes that Ecstasy, given in a carefully controlled clinical psychotherapeutic setting, might have value in the treatment of post-traumatic stress disorder, but he doesn’t support legalisation of Ecstasy for general, recreational use. A year before Senator Biden introduced the RAVE Act, Grob testified before the US Sentencing Commission. His remarks included the following:
‘Carefully examining the record of human research with MDMA, particularly the NIDA-funded studies of George Ricaurte, one observes a persistent pattern of poorly controlled studies, often with deliberate exclusion of vital data sets from published reports as well as unreported pre-selection biases in criteria used to recruit research subjects, which have led to grossly exaggerated and misleading claims in the scientific literature and in the media.’
Unperturbed by such criticism, Ricaurte pushed his Ecstasy research in a new direction. Earlier reports in the scientific literature, based on experiments in rodents, suggested that Ecstasy might also have damaging effects on neurons that used dopamine – the other transmitter whose release is triggered by Ecstasy. The doses needed to produce the toxic dopamine effects were rather high, and the damage didn’t appear to be as great as the damage suffered by the serotonin system. In 2000, however, Ricaurte set out to establish whether Ecstasy, even when given in a dose comparable to what a person might consume in the course of a single rave, could damage dopamine neurons in the brains of monkeys. Ricaurte gave pure MDMA (Ecstasy) to five squirrel monkeys and five baboons. Most of the animals received three doses of the drug, spaced at three-hour intervals. The total dose was six milligrams per kilogram of body weight. This would correspond to a person taking three pure Ecstasy tablets of about 150 mg each in the course of a single night’s partying – an amount that is within the range of what some rave attendees might consume, though probably higher than the typical user’s consumption. Because dosing monkeys orally is inconvenient – monkeys often reject food that has been spiked with drugs – Ricaurte gave the animals their MDMA doses by subcutaneous injection.
Two of the animals – one squirrel monkey and one baboon – developed uncontrollable hyperthermia soon after their final dose, and they died within hours. Another two monkeys – again, one of each species – fell ill after their second doses, and were therefore not given their final dose. The four surviving animals of each species were allowed to live for two to eight weeks, and then killed so that their brains could be studied, along with those of several control animals who had received injections of saltwater.
The results were striking: the monkeys that had received MDMA, even those who only received two of the planned three injections, showed signs of profound damage to the dopamine systems in the brain. Contrary to what might have been expected on the basis of previous studies, the damage to the dopamine system was even more severe than the damage to the serotonin system. And it wasn’t just a reduction in the levels of dopamine-related molecules, though that had certainly happened. In addition, Ricaurte found that the nerve endings of the dopamine neurons were physically degenerating. The cell bodies may have survived, but their terminals – the all-important sites of transmitter release – were shrivelling and dying like autumn leaves. And in response to the destruction, a special set of inflammatory cells were enlarging and multiplying in the affected areas of the brain. It seemed like the kind of thing that could give an Ecstasy abusing partygoer the morning after from hell.
As has already been discussed in the first chapter of this book, the loss of brain dopamine function is a central feature of Parkinson’s disease, the movement disorder that strikes between 8,000 and 10,000 Britons every year and that ends up killing many of them. So the finding of severe damage to the dopamine system in his monkeys’ brains immediately provoked an alarming thought in Ricaurte’s mind: could people who indulged in a single night’s use of Ecstasy be setting themselves up for a lifetime of Parkinson’s disease?
