The Lancet,
Volume 375, Issue 9723, Page 1319, 17 April 2010
A collapse in integrity of scientific advice in the UK
The Lancet
Over the past 6 months the UK's Advisory Council on the Misuse of Drugs (ACMD)-an independent expert body that advises government on drug-related issues-has hardly been out of the headlines. One sacking and seven resignations is not a good track record for any organisation.
The public's discontent at the ACMD over how it operates and how it is unduly influenced by government has left a bitter taste, together with a crisis in confidence about evidence-based policy making in the UK.
The trouble at the ACMD began in October, 2009, after the controversial sacking of the then chairman, Professor David Nutt for criticising the government's policy over cannabis and ecstasy. Five more members quit soon after in protest. In January, 2010, the equally distinguished neuroscientist, Professor Les Iverson, was appointed interim chair. In March, 2010, Dr Polly Taylor was the next to leave, outraged by the publication of the revised Code of Practice for Scientific Advisory Committees, the rewording of which compromised scientists' independence and would dissuade them from giving objective advice lest they disagreed with government policy.
The current outcry at the ACMD is over the recreational drug mephedrone (4-methylmethcathinone), a synthetic stimulant most similar chemically to amphetamines. It is a derivative of cathinone, a compound found in the plant called khat. Clinical and pharmacological research on cathinones is sparse and knowledge about the human effects of this drug class have been reliant on anecdotal reports from users and physicians.
Adverse reactions include tachycardia, hallucinations, vasoconstriction, increased anxiety, and possible psychosis. The substance has received substantial media attention in the UK after reportedly being linked to
25 deaths. Indeed, the ACMD has suggested that media coverage has increased the use of the drug.
The most recent resignation was Mr Eric Carlin in response to the reclassification of mephedrone to class B together with its subsequent ban alongside other cathinone derivatives. According to Carlin, the decision-making process focused primarily on the chemistry and legality of the drugs, and too little on the public health measures that could reduce harm. Furthermore, the ACMD report, Consideration of the cathinones, which recommended the ban, documented the very scanty evidence on mephedrone, including the absence of a direct causal link between the reported deaths and the drug. Alarmingly, the report, which was only a draft, was still being discussed by the ACMD when Iverson rushed out of the meeting to brief Home Secretary Alan Johnson of their recommendation in time for a press briefing. Carlin states on his blog:
"We were unduly pressured by media and politicians to make a quick, tough decision to classify."
Equally notable was the very quiet release on the same day of the ACMD's other report, Pathways to Problems-a detailed progress report on recommendations made in 2006 on hazardous drug use. The report contains some potentially unpalatable conclusions on tackling young people's problems, including not enough being done on alcohol and tobacco, as well as calling for a review of the Misuse of Drugs Act 1971. Yet this report received no media attention or a response from the Home Office.
Instead, it conveniently got buried under discussions on the legal status of mephedrone.
There was little time to consider carefully the scientific evidence on mephedrone. The ACMD did not have sufficient evidence to judge the harms caused by this drug class. It is too easy and potentially counterproductive to ban each new substance that comes along rather than seek to understand more about young people's motivations and how we can influence them. We should try to support healthy behaviours rather than simply punish people who breach our society's norms. Making the drug illegal will also deter crucial research on this drug and other drug-related behaviour, and it will be far more difficult for people with problems to get help.
The terms of engagement between ministers and expert advisers endorsed by Alan Johnson have been blown apart. During the past 12 years the Labour Government has done a great deal to build up a strong science base in the UK and enhance the important role that science plays in our economy and society. However, the events surrounding the ACMD signal a disappointing finale to the government's relationship with science.
Politics has been allowed to contaminate scientific processes and the advice that underpins policy. The outcome of an independent enquiry into the practices of the ACMD, commissioned by the Home Office in October, 2009, is now urgently awaited. Lessons from this debacle need to be learned by a new incoming government.
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UK places generic ban on mephedrone drug family
Kelly Morris
Debate over how to reduce the harms caused by recreational drugs has been ignited by the UK Government's decision to ban mephedrone and related cathinones. Kelly Morris investigates.
The exceptionally rapid rise in use of mephedrone and related cathinone derivatives in the UK has caused the Home Secretary Alan Johnson to ban the substances, within the same class as amphetamines (class B), on the recommendation of the Advisory Council on the Misuse of Drugs (ACMD).
The ban, expected to be implemented on April 16, is thought to be the world's first generic ban of a group of cathinones based on chemical structure. Experts say that they will be watching the effect of the ban on the drug family that includes mephedrone-suspected to be involved in up to 25 deaths in the UK, most awaiting inquest.
However, the recommendation about cathinones has spurred controversy over how to reduce drug harms. Eric Carlin, who is researching young people, social disadvantage, and resilience at Birkbeck College, University of London, UK, resigned from the ACMD on April 1, stating that his "substantial experience of managing drug prevention and treatment services" had not helped influence the committee, and thereby the government, "to think about drugs as more of a public health issue rather than focusing narrowly on the criminal justice aspects". In regard to mephedrone, Carlin stated that the ACMD "had little or no discussion about how our recommendation to classify this drug would be likely to impact on young people's behaviour". Carlin is concerned about the potential criminalisation of young people by the ban.
Cathinone derivatives are synthesised by modifications to cathinone-an illicit molecule found in the khat plant, which is structurally very similar to amphetamine. The derivative methcathinone is chemically analogous to methamphetamine, and methylone to MDMA (ecstasy).
Mephedrone (4-methylmethcathinone), which has no amphetamine analogue, is the most commonly seized derivative. Effects are reportedly similar to those of cocaine, amphetamine, and MDMA. According to a survey in the dance magazine MixMag, done by Adam Winstock from the National Addiction Centre, London, UK, and colleagues, mephedrone was the fourth most commonly used drug in the past month by respondents. 41·7% of more than 2000 respondents indicated they had ever used mephedrone, with 10·8% reporting use of methylone. Further findings from mephedrone users are expected to be published soon.
Mephedrone was first highlighted by the UN Office on Drugs and Crime after the death of an 18-year-old Swedish woman, reported in December, 2008, in which mephedrone was the only substance detected post mortem.
David Gustavsson, now at University Hospital of Malmö, Sweden, who was involved in the patient's emergency care, told The Lancet: "When I first started to look into mephedrone, I was struck by the fact that no reliable information was available at all." Some cathinone derivatives are known to inhibit reuptake of monoamine transmitters, but such research has not been done on mephedrone. Acute toxicity reports include CNS hyperstimulation, cardiovascular compromise, and serotonin syndrome, the latter usually with concomitant prescribed selective serotonin reuptake inhibitors. Mephedrone also has been implicated in causing hallucinations, anxiety, paranoia, seizures, and delusions. Gustavsson notes that without research "one can hardly say anything for sure about anything, specifically regarding the long-term effect of mephedrone".
The experience of mephedrone in Sweden shows that many users regard mephedrone "as a fully acceptable substitute for ecstasy and amphetamine/cocaine", Gustavsson explains. "Some experienced patients had even stopped using these drugs when they discovered mephedrone and its appreciated effect." But others have been concerned about dependency, he says. From clinical experience at Maria Ungdom in Stockholm, Sweden, a publicly funded clinic for people younger than 20 years in Stockholm county, users describe an effect in between amphetamine and ecstasy. Gustavsson explains: the peak effect, after about 20-30 min, "is followed by a strong urge to administer a new dose, an urge so strong that it surprised many experienced drug users."
Gustavsson questions whether experimentation with unstudied substances, especially by inexperienced young people, is because of the misconception that legality implies safety. Winstock also points to the large market of users who are dissatisfied with illicit stimulants and interested in substances with a desired profile of effects, availability, and perceived value for money. Users and community workers suggest that the unavailability or low purity of cocaine and MDMA-related to international control measures-"have contributed to the increase in mephedrone use", the ACMD cites. Additionally, cathinone derivatives are so-called legal highs and widely available from internet websites, sold as bath salts or plant food, not for human consumption.
Sweden is among several countries that have now banned or controlled mephedrone. Gustavsson recalls that mephedrone use was more frequently reported at Maria Ungdom from mid-2008, including several users who had encountered "unusual" difficulty stopping mephedrone compared with other drugs. By autumn, 2008, "mephedrone was by far the most popular legal drug sold on the internet in Sweden", he recalls. Mephedrone was classified as hazardous in Sweden in December, 2008, which restricted internet sale. Subsequently, anecdotal evidence suggests that mephedrone began to be sold person-to-person rather than on the internet, he says.
Stefan Sparring, senior consultant at Maria Ungdom, describes what happened after mephedrone was classified as hazardous: "the drug quickly moved to the illicit trade in the streets, and we still saw new cases every week. In the spring of 2009 it was classed as a narcotic and after that we thought we could see a trend of it disappearing." However, Sparring still sees new cases related to mepehdrone use every week.
"What we now also see is the true emergence of 'designer drugs", he notes. After mephedrone became illegal, methodrone flooded the market, he says. Methodrone has since been implicated in two deaths and banned in Sweden. Now, says Sparring, "we have flephedrone instead, and it just continues".
Experience with several former legal highs shows that legislation against one legal high can result in the rebranding or development of an unsanctioned alternative, Winstock notes in an online editorial with John Ramsay from St George's University, London, UK, in the journal Addiction. Substances have been produced and marketed with the explicit aim of circumventing legislative restrictions for several decades, they note. "What has changed is an increase in their range, potency, profile and availability. The development of global web-based marketing and distribution networks, as distinct from illegal street markets, has emerged concurrently, challenging further the utility of existing supply reduction strategies." The ACMD now plans to review the naphthyl analogue of pyrovalerone, which is advertised on the internet and retailed as NRG-1.
Experts will be following the adoption of the generic law with interest, says Winstock, assessing its effect on use, harms, and the illicit and licit marketplace. "The lesson we need to learn is, in the case of such drugs, what is the impact of different interventions in harm and use?"
he told The Lancet. When a drug is made illegal, controls are limited to supply reduction and keeping harm to a minimum, Winstock and Ramsay write. "While in no way does 'legal' confer relative safety, it does mean that a broader repertoire of responses is available", they note.
In his resignation letter, Carlin describes his concern about the effect of the UK legislative framework on the work of the ACMD. A further concern of Carlin's is the lack of attention to the ACMD Pathways to Problems follow-up report, which contains wide-ranging recommendations for tackling young people's problems with drugs, including alcohol and tobacco. The report was released on the same day as the ACMD review about cathinones but was not covered in Home Office media statements. In the report's recommendations, the ACMD calls for a review of the Misuse of Drugs Act 1971.
The ACMD will soon report on the possible control of legal highs.
However, one unintended consequence of present medicines legislation is to leave distributors unable to disclose the true purpose of their product, Winstock and Ramsay note. "General common sense precautions that apply to any psychoactive drug cannot be given without risking prosecution", they write. "The dilemma is what to do between the appearance of a problem, risk assessment, and the inevitable but uncertain legislative response."
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