Drowning in diversity? A systematic way of clustering and selecting a representative set of new psychoactive substances

Published by the Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.New psychoactive substances (NPS) can be generally described as a set of compounds that have been designed to mimic the effects of illegal recreational drugs, but are not subject to restriction or control with respect to existing regulation and legislation. In recent years, the number and chemical diversity of emergent NPS has increased substantially, and regulators have struggled to develop methods for accurate detection of NPS at the same rate. Existing approaches to NPS classification are pragmatic and/or semi-systematic and do not lend themselves to objective spectroscopic classification of emergent NPS. As such, this research discusses the identification of a systematic NPS classification based on chemical structures. A set of 478 NPS were grouped according to the similarity between their chemical structural features using hierarchical clustering and a maximum common substructure of 9 atoms, which included both hydrogen and heavy atoms. The rationale for including hydrogen atoms is that accurate spectroscopic identification of NPS will be dependent upon variations in substitution patterns in the molecules. This analysis generated 79 clusters, arising from 21 superclusters. The medoid substances of each cluster were used to form a dataset that was representative of the chemical space encompassed by known NPS. Subsequent categorisation of a test set of NPS showed that the test substances were assigned to an appropriate cluster when the Tanimoto similarity coefficient between the cluster medoid and the test substance was at least 0.5. This indicates that the cluster medoids could be used for assignment of emerging NPS to systematically-defined categories based on chemical structure. These medoids will also aid in the prediction of spectroscopic properties for emergent NPS, which will be invaluable for structure-based classifications and development of methods for detection of emerging NPS.Peer reviewe

Heroin-assisted treatment in Switzerland: a case study in policy change

BACKGROUND: Switzerland introduced a pragmatic national drug policy when the former conservative abstinence-orientated politics proved unable to cope with an escalating number of users and related negative consequences for public health and public order. The high visibility of 'needle parks' and the size of the acquired immune deficiency disorder (AIDS) epidemic called for a new approach and for national leadership. AIMS: To describe the intentions, the process and the results of setting up the new treatment approach of prescribing heroin to treatment resistant heroin addicts, as an example of drug policy change. MATERIALS AND METHODS: A systematic collection of relevant documents is analysed and used as evidence for describing the process of policy change. RESULTS: Measures to reduce the negative consequences of continued use and to prevent the spread of AIDS were started mainly by private initiatives and soon taken up officially in the 'four-pillar' drug policy (including harm reduction, prevention, treatment and law enforcement). Medical prescription of heroin to chronic, treatment-resistant heroin addicts was one of the innovations, based on extensive scientific and political preparation. Detailed documentation and evaluation, ample communication of results, adaptations made on the basis of results and extensive public debate helped to consolidate the new policy and heroin-assisted treatment, in spite of its limitations as an observational cohort study. All necessary steps were taken to proceed from a scientific experiment to a routine procedure. DISCUSSION: Comparable policy changes have been observed in a few other countries, such as The Netherlands and Germany, based on the Swiss experience, with equally positive results of heroin-assisted treatment. These experiments were designed as randomised controlled trials, comparing intravenous heroin against oral methadone, thereby demonstrating the specific value of pharmaceutical diamorphine for maintenance treatment in opiate dependence. The positive impact of policy change and the positive outcomes of heroin-assisted treatment were acknowledged increasingly nationally and internationally, but made it difficult to continue the process of adapting policy to new challenges, due to the low visibility of present drug problems and to changing political priorities. CONCLUSION: A major change in drug policy was effectively realised under typical conditions of a federalist country with a longstanding tradition of democratic consensus building. Facilitating factors were the size and visibility of the heroin problem, the rise of the Aids epidemic, and a pragmatic attitude of tolerating private initiatives opening the way to official policy change