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‘Spice’ is a herbal mixture sold on the internet, samples of which have been found to contain new synthetic drugs which produce effects similar to cannabis. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)'s early warning system on new drugs provides an important case study in how globalization and innovation present challenges to drug control. The story of ‘Spice’ provides an important case study in how globalization and innovation in the drug market presents a growing challenge to current approaches to monitoring, responding to and controlling the use of new psychoactive substances. ‘Spice’ is a herbal mixture sold principally on the internet, and in some countries in specialist shops offering legal alternatives to controlled substances. The packaging is sophisticated, and many different mixtures have been released under the generic ‘Spice’ brand. These often exotically named mixtures, such as ‘Spice Gold’, ‘Diamond’ and ‘Silver’, purportedly contain different combinations of herbs, some of which may have psychoactive properties. The products have probably been available in Europe since 2004, if not earlier, but they only started to attract wider attention in 2007, and began to be monitored by the European early warning system on new drugs during the first months of 2008 1. This mechanism is part of a Europe-wide three-step approach of information exchange/early warning; risk assessment; and decision-making for the detection and possible control of new psychoactive substances. ‘Spice’ is sold under a number of guises, commonly as an exotic incense blend, and usually contains a warning note stating that it is not for human consumption. This information is juxtaposed with sophisticated marketing that would suggest that it may have other uses. The use and marketing of herbal mixtures is not new, and a range of non-controlled plants and fungi are sometimes used for their psychoactive or supposedly psychoactive effects. ‘Spice’ stands out not only because of the sophistication of the packaging and the complicated blends of substances that it is purported to contain. It also stands out because some of those who used the drug reported effects similar to or even stronger than those obtained by smoking cannabis. The veracity of these reports was difficult to judge, as they came mainly from online forums. However, this underlines the importance of the internet, not only as a source for ‘Spice’ but also for marketing and raising awareness about the product. A parallel can be drawn here with modern viral marketing techniques, which attempt to use social networking as a tool for encouraging new brands to be adopted, especially by what are regarded as socially influential individuals, early adopters and trend leaders. Although non-controlled plant products are clearly attractive to some users—khat and salvia (Salvia divinorum) spring to mind—in general, many of the products marketed as legal highs struggle to compete with controlled drugs khat is controlled in some jurisdictions but the plant is not listed in the international drug control conventions and in many countries is not subject to control. This is arguably because they often do not meet users' expectations, perhaps because they deliver unpleasant or only mild effects. However, in 2008 the suggestion that ‘Spice’ was different slowly began to attract attention, first from the media and then from policy makers and researchers. Initially, concern about ‘Spice’ was focused on a few central European countries, although internet monitoring would suggest that consumer interest had spread far wider than this, extending beyond the European Union and even into Russia. A detailed review of the identification, availability and marketing of ‘Spice’ can be found at EMCDDA 2. The initial problem facing the analysis of ‘Spice’ was to determine exactly what was in it. ‘Spice’ purported to contain up to 15 different herbs, of which wild dagga (Leonotis leonurus) and Indian warrior (Pedicularis densiflora) were viewed as the most likely candidates for causing a psychoactive effect. In a self-administration experiment, German researchers were surprised at the potency of the sample tested 3. However, detailed chemical analysis failed to find any of the herbal substances expected from the product labelling. What they did eventually manage to identify, on 16 December 2008, using nuclear magnetic resonance spectroscopy, was the presence of a synthetic cannabinoid, the cyclohexylphenol CP 47 497 and one of its active homologues 2, 4, 5. Just one day earlier a company undertaking analysis of the product for the city council of Frankfurt had also identified the synthetic cannabinoid naphthoylindole, JWH-018 3, 6. This was a lucky break, as it resulted from comparing one of the unknown mass spectra generated by a ‘Spice’ sample to a JWH-018 reference sample they happened to have in stock. Since then nine synthetic cannabinoids have been found in ‘Spice’ or ‘Spice’-related products in Europe 2, 7 and in the United States 8 and Japan 9. A review of these compounds can be found at http://www.emcdda.europa.eu/publications/drug-profiles. Identification of these products has been hampered by the lack of reference samples of these obscure chemicals. It is also possible that masking agents such as tocopherol (vitamin E) were added to confound detection 2. The appearance of synthetic cannabinoids can be seen as a new phase in the development of what is sometimes known as the ‘designer drug’ market. Attempts to develop legal alternatives to controlled substances are not new, but they have evolved considerably. ‘Designer drugs’ based on fentanyl appeared in the early 1980s, followed by ring-substituted phenethylamines in the late 1980s and tryptamines in the 1990s. Since 2000, we have increasingly seen piperazines and cathinone derivatives exploited for this purpose. However, in 2008, with JWH-018, for the first time ever a synthetic cannabinoid was reported to the European early warning system. This mechanism monitors trends in the availability of non-controlled substances, and can trigger a more formal risk assessment and legal control response. This is a worrying development, as there are more than a hundred compounds with cannabinoid activity. The cannabinoids found in ‘Spice’ are just two among a large number of obscure chemicals with CB1 or CB2 receptor agonist activity, and which can be expected to produce cannabis-like effects. Some of these may be full agonists and considerably more potent than natural cannabinoids—with the consequence that they can produce the same effect as larger doses of tetrahydrocannabinol (THC). Virtually nothing is known about the health implications of consuming these drugs, either in man or animals. However, serious consequences 10, including the possibility of overdose, cannot be ruled out. More generally, the emergence of these substances points to the fact that recent developments that permit cheap organic chemical synthesis are being exploited by chemists seeking out attractive new substances for the recreational drug market. In contrast to the undeclared ingredients of ‘Spice’, the psychoactive plants listed on the product label have hardly been detected. Although some herbal mixtures may contain the plants stated, most samples of ‘Spice’ tested appear to contain inert vegetable matter. Although little is known about the manufacture of ‘Spice’, the synthetic compounds that are sometimes present seem to have been added surreptitiously to the mixtures at their production sites, which appear to be in Asia. This raises the difficult question for policy makers, both practically and morally, of whether ‘Spice’ should be addressed as a consumer protection or drug control issue. Most of the attention received by ‘Spice’ has been in European Union (EU) countries, in part because of the mechanism that exists to respond to potential new drug threats. Nevertheless, it is very much a global phenomenon. Any control measures considered are faced with the regulatory difficulties presented when products are available from the internet, where national jurisdictions can be circumvented easily. This can also lead to anomalies. Internet retailers of ‘Spice’ based in the Netherlands, for example, can supply ‘Spice’ products to other EU countries but not their own. Moreover, the development and production of ‘Spice’, as far as we are able to ascertain, took place in countries in the developing and transitional world—again where regulatory mechanisms may be weak or difficult to enforce. The ‘Spice’ case study poses difficult questions about how we monitor and respond to drug use. Europe has invested in developing an early warning system on new drugs and information exchange is now possible in a way that would have been difficult in the past. However, no central reference laboratory exists or mechanism for making reference samples is available. This is important, as identification of the active ingredients in ‘Spice’ was complicated by the lack of reference material. Also, as there is no current proactive testing of this type of product, it was only after a considerable time that it became visible to the authorities and sufficient concern was generated to launch an investigation. That this type of product falls into a grey area between commercial products, medicines and illicit substances also meant that there was a lack of clarity regarding which agencies should take responsibility for this issue. This conceptual issue is also mirrored in the attempts that some countries have made to control ‘Spice’ by using a variety of instruments, including medicines legislation and formal drug control measures 11, 12. Even if one adopts the view that ‘Spice’ should be viewed simply as a consumer product, the fact that a substance was being consumed which contained a unlisted psychoactive ingredient, which is largely untested and not known to be safe, is clearly a cause for concern. A minimum public health response would be to warn consumers that the product contained unlisted compounds. However, this course of action is not uncontested, as concerns have been raised that drawing attention to this fact may increase interest in the product. Some of the synthetic chemicals that had been added clandestinely to ‘Spice’ mixtures have, in a few months, gone from being virtually unknown research chemicals, for which forensic science laboratories had difficulties in identifying and obtaining reference samples, to being commercially marketed in their own right. For those with the right knowledge, significant amounts of highly psychoactive chemicals can be obtained cheaply and legally with a few clicks of a mouse. The speed and sophistication of innovation in this area is impressive and also serves to highlight the sluggishness and clumsiness of most attempts at control. ‘Spice’ itself may be a transient product, but it provides an excellent case study of how the globally connected world in which we now live is challenging existing models of drug control. The authors would like to thank Peter Fay for his helpful comments on the text and acknowledge the work of those scientists who attended the EMCDDA's expert meeting on ‘Spice’ held in Lisbon, on 6 March 2009, the deliberations of which were the inspiration for this piece. None.
Griffiths et al. (Thu,) studied this question.