We thank Caldicott and colleagues for their thoughtful and detailed response to our article [1,2]. We agree, as stated in our article, that the results of our findings need to be interpreted with caution and that there may be a number of explanations for the observed decrease in the number of presentations to our Emergency Department with acute mephedrone toxicity subsequent to the UK classification of mephedrone in April 2010. British Crime Survey data has shown substantial continued use of mephedrone since it was classified in the UK in April 2010 and other survey based datasets also suggest continued use of mephedrone [3,4]. Despite this, our results showing decreased presentations with acute mephedrone toxicity are not unique and other, national, datasets from both the UK National Poisons Information Service (NPIS) and National Programme on Substance Abuse Deaths (np-SAD) have shown similar results [5,6]. There were substantial reductions in both enquiries to the NPIS telephone service and hits on the online TOXBASE NPIS service regarding mephedrone after April 2010. In addition, data collected by np-SAD has demonstrated a decrease in both suspected and confirmed mephedrone related fatalities since April 2010. We agree with Caldicott that the changes in presentations to our Emergency Department with acute mephedrone toxicity and potentially those seen in these national datasets are associations and do not imply causality related to the legislation. In the field of novel recreational drug toxicity, in which there is a paucity of published data, it is important that systematic information from all sources is considered to establish the changes in epidemiology and patterns of toxicity associated with these drugs. We agree with Caldicott and colleagues that it is important for clinicians to work together in this area and commend their efforts in setting up the WEDINOS group. David M Wood Consultant Physician and Clinical Toxicologist, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK Senior Lecturer, King's College London Shaun L Greene Senior Clinical Fellow, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK Paul I Dargan Director for Clinical Toxicology and Consultant Physician and Clinical Toxicologist, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK Reader, King's College London References 1. Caldicott DGE, Hobbs R, Hutchings A, Westwell A. Mephedrone Legislation- Causality or coincidence?. Published 2 Dec 2011.

Conflict of Interest:

None declared

We read with interest the short report by Wood et al[1], and support the idea of the Emergency Department as an observatory for emerging licit/illicit novel substances. We would caution however, against the assumption that legislation has a significant impact on the consumption patterns of young drug users. For that assumption, one would require significantly more data, from a much wider range of EDs than the relatively small numbers provided in their report. In our data set of 138 cases over two hospital sites, there have been 2 subsequent spikes in presentation following the banning of mephedrone, and no real signs of long-term abatement. The only effect of the ban that we could identify was a surge in presentations related to the drug, immediately prior to its ban- this also appears to be the case in Woods et als data. One could argue that the high profile announcement of the ban of mephedrone, and the associated media coverage[2] actually caused the spike in consumption, in ingénues unfamiliar with the product and keen to sample it prior to it becoming illegal. As consumers became more familiar with the less desirable, but nevertheless predictable side effects of the drug, it is possible they became less inclined to seek medical care. Even worse, it may be that consumers became reluctant to seek medical care for the effects of a now-illegal product, for fear of recriminations. Our findings reflect those of others[3], providing very little evidence that the ban on mephedrone has had any meaningful impact on its consumption. Even if the pattern of ED presentations seen by Woods et al is merely a local one, it doesn’t necessarily imply that that is a ‘good thing’ for their population. It has been suggested that the increased use of mephedrone had resulted in a reduction of cocaine related deaths in 2009[4]- has that reversed? The likeliest reason for the diminution in the use of mephedrone is the fickle nature of the market itself, rather than any legislation, with consumers of legal highs moving on to whatever next big thing is waiting in the wings. Experience has shown, as in the cases of p-methoxyamphetamine (PMA)[5] and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)[6], that the next ‘big thing’ might not be a ‘better’ thing, but may in fact have effects far worse that those of its banned predecessor. In an effort to avoid such oversimplifications, the Welsh Emergency Department Investigation of Novel Substances (WEDINOS) has set up a programme of systematically identifying potential novel products as they present to the emergency departments of Wales. A three pronged approach of chemical characterization of substances arriving at the Emergency Department, epidemiological tracking using GIS software, and the planned introduction of on-site rapid patient interventions allow for patterns of harm associated with consumption to be definitively delineated. There is very little evidence that the simple ‘banning’ of any recreational product has ever had a significant impact on its availability. To assume that anything is different with mephedrone seems a little naïve. The real hazard of the legal high market are not the individual drugs themselves, but the rapid cycling of products that leaves clinicians, toxicologists and legislators alike bewildered in its wake, and the potential for the emergence of something profoundly dangerous in the evolutionary crucible that is the current online market. Interdiction is a very crude tool to manage the subtle nuances of the ‘legal highs’ market, and data provided in the form that it has by the authors, with unsophisticated attributions of causality, are usually the remit of government departments. This report will certainly be seized upon by political bodies as a justification for action; whereas it might reflect the efficacy of government interventions in London SE1, we remain to be convinced of its validity elsewhere. 1. David M Wood, Shaun L Greene and Paul I Dargan Emergency department presentations in determining the effectiveness of drug control in the United Kingdom: mephedrone (4-methylmethcathinone) control appears to be effective using this model Emerg Med J published online October 27, 2011 doi: 10.1136/emermed-2011-200747 2. Editorial (2010). "A collapse in integrity of scientific advice in the UK". The Lancet 375 (9723): 1319–1319. 3. McElrath K, O'Neill C. Experiences with mephedrone pre- and post-legislative controls: perceptions of safety and sources of supply. Int J Drug Policy. 2011 Mar;22(2):120-7 4. Daly, M. (September/October 2010). "Booze, bans and bite-size bags". Druglink. Drugscope. pp. 6–9. http://www.drugscope.org.uk/Resources/Drugscope/Documents/PDF/Publications/DruglinkSept-Oct2010.pdf. Retrieved 2011-01-29. 5. Caldicott DG, Edwards NA, Kruys A, Kirkbride KP, Sims DN, Byard RW, Prior M, Irvine RJ. Dancing with "death": p-methoxyamphetamine overdose and its acute management. J Toxicol Clin Toxicol. 2003;41(2):143-54. 6. Fahn, Stanley. The Case of the Frozen Addicts: How the Solution of an Extraordinary Medical Mystery Spawned a Revolution in the Understanding and Treatment of Parkinson's Disease. The New England Journal of Medicine. Dec 26, 1996. Vol. 335, Iss. 26; pg. 2002