Elsevier

Toxicology Letters

Volume 197, Issue 3, 1 September 2010, Pages 157-162
Toxicology Letters

Mini review
Spice drugs as a new trend: Mode of action, identification and legislation

https://doi.org/10.1016/j.toxlet.2010.06.002Get rights and content

Abstract

The present review highlights the existing monitoring and legislation status of synthetic cannabinoids in “Spice” products and alert research community about the identification and risk assessment problems of these compounds. Available data were collected by various literature search engines. All valuable information about psychoactive properties, safety profile, clinical data and detection problems for synthetic cannabinoids and their use as “herbal highs” were managed to spot and summarise. “Spice” contains synthetic cannabinoids that bind to cannabinnoid-like receptors and they are stronger than natural cannabis. Chronic abuse of “Spice” has linked with signs of addiction syndrome and withdrawal symptoms similar to syndromes observed in cannabis abuse. These cannabinoids can be considered as new products to be added to the list of “designer drugs”. Although it remains unclear where and how the actual production of the herbal mixtures takes place, it is evident that producers are purposely risk the health of consumers to skim high profits. Only recently a number of countries in Europe, as well as in US and Canada banned the use of these substances. The difficulty in identification of related compounds leads to the necessity for the availability of reference standards in order to aid toxicological analyses.

Introduction

A number of classical cannabinoids, Δ9-THC analogs, have been synthesized based on its partially reduced dibenzopyran structure (Uchiyama et al., 2009). At the end of 2008, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and Europol, found that a “smoking mixture” under the brand name “Spice” was not the herbal product that it purported to be (EMCDDA, 2008). Although “Spice” was declared as “incense blend which releases a rich aroma” and “not for human consumption”, when smoked as “bio-drug”, has been reported by some users to have effects similar to those of cannabis (Auwärter et al., 2009). “Spice” and other “herbal” products are often referred to as “legal highs” or “herbal highs”, in reference to their legal status and purported natural herbal make-up (McLachlan, 2009, Lindigkeit et al., 2009, Zimmermann et al., 2009).

A variety of “Spice” products e.g.: Spice Silver, Spice Gold and Spice Diamond, etc. (Auwärter et al., 2009), are mixtures (blend) reported to contain the following plant/herbal ingredients: Indian Warrior, Lion's Tail, Baybean, Blue Lotus, Vanilla, Honey, etc. Based on their chemical compositions, it can be assumed that, at least two of these ingredients, “Indian Warrior” and “Lion's Tail”, may have some psychoactive effect. On the packaging of the “Spice” products, there is a lack of information about the complete chemical composition and little is known about the toxicology of the plant materials purportedly contained in the “Spice” products. Thus, no definite answers can be provided at present, with regard to the potential health risks related to the possible psychoactive effects, but also in general for these products (EMCDDA, 2008).

In December 2008, chemical analysis revealed that the psychoactive effects of the herbal mixtures were due to added synthetic cannabinoids. Synthetic cannabinoids that have been reported in “Spice” and “Spice”-like samples in Europe are JWH-018, JWH-073, JWH-398, JWH-250; HU-210; CP-47,497 and its homologues; and oleamide. The above Cannabinoids1/Cannabinoids2 receptor (CB1/CB2) agonists are lipid-soluble, non-polar, with typically 20–26 carbon atoms, which are fairly volatile. Although, their detailed pharmacology has not been investigated, it's a fact that many of them are much more potent than Δ9-THC, therefore the usual doses may be less than 1 mg (EMCDDA, 2009a, EMCDDA, 2009b).

There is no evidence that JWH, CP and/or HU compounds are present in all “Spice” products or even batches of the same product. Different amounts or combinations of these substances seem to have been used in different “Spice” products to produce cannabis-like effects. It is possible that substances from these or other chemical groups with a cannabinoid agonist or other pharmacological activity could be added to any herbal mixture (Griffiths et al., 2010).

Up to now, the mixtures are sold in headshops and via Internet in many countries. In several Internet blogs, drug users reported cannabis-like effects after smoking “Spice” mixture. These products are sold without age restriction of the clients and for that enjoy great popularity particularly among younger people (Auwärter et al., 2009).

This review aims to summarise any available information about psychoactive properties, safety profile, clinical data, detection problems and legislation for synthetic cannabinoids and their use as “herbal highs”.

Section snippets

Cannabinoids and their receptors

Cannabinoids are a structurally diverse family of compounds with a large number of biological targets. Based on their origins, cannabinoids, can be classified into three groups: phytocannabinoids, endocannabinoids, and synthetic cannabinoids (Sun and Bennett, 2007).

Phytocannabinoids are only known to be present in significant quantity in the cannabis plant (Grotenhermen, 2004). The smoke from burning cannabis contains various chemicals (Goodman and Gilman's, 2001). The most prevalent natural

JWH-018

JWH-018 is the first synthetic cannabinoid ever reported through the Early Warning System (EWS) during 2008 (EMCDDA, 2008). JWH-018 is prominent component of several herbal preparations and is an effective CB1 receptor agonist that activates multiple signalling pathways. Thus, it is likely that the subjective effects of “Spice” are due to activation of cannabinoid CB1 receptors by JWH-018, added to this herbal preparation (Mechoulam et al., 1988).

Despite the absence of clinical data in humans,

Tracking the World Wide Web and Patterns of use

Tracking the World Wide Web (www), it is clear that “Spice” products are generally used by teenagers and young people, who are interested in using psychotropic drugs. There are reports that “users recommend using pipes” and that “the fumes of the burning mixture could be inhaled”. “Spice” products can be smoked, sometimes together with cannabis or consumed orally as an infusion (EMCDDA). Those smoking blends are so widespread that the results were even found in a smoking blend comparison, for

Case reports

A limited number of clinical reports clearly demonstrate signs of addiction and withdrawal symptoms that were linked to the chronic abuse of “Spice”, similar to syndromes observed with cannabis abuse.

Case 1: Zimmermann et al. (2008), presented a case of a 20-year-old patient who reported that for the last 8 months he had been inhaling the smoke of “Spice Gold” initially 1 g daily.

The patient described that “Spice Gold” acted similarly to cannabis but with “Spice Gold” experienced strong

Identification of synthetic cannabinoids in “Spice” products

According to the EMCDDA Report on “Spice” extensive toxicological investigations were undertaken in Germany and Austria for the identification of “Spice” products ingredients. Chemical analyses have revealed that the psychoactive effects of the herbal mixture were due to added synthetic cannabinoids. Several analytical laboratories in Europe (Germany, Austria, Finland, France, Hungary, Poland, Slovakia, Slovenia and the United Kingdom) have confirmed the presence of synthetic cannabinoids in

Legal status

Products containing HU-210 and similar cannabinoids are controlled in a number of countries, including Austria (3rd March 2009), Germany (22nd January 2009), the Netherlands, Switzerland, Canada (Intelligence alert, 2009) and UK (23rd December 2009) (http://drugs.homeoffice.gov.uk/news-events/latest-news/control-of-legal-highs-dec09.html).

Furthermore, responding to potential health concerns, France (24th February 2009), Hungary (9th March 2009), Poland (8th May 2009), Luxembourg (4th May 2009),

Discussion

“Spice” products contain synthetic cannabinoids that bind to cannabinnoid-like receptors and they are stronger than natural cannabis. These cannabinoids can be considered as new “designer drugs”.

It remains unclear where and how the actual production of the herbal mixtures, synthetic cannabinoids and their addition to the herbal mixture takes place. It can be assumed that the producers buy cannabinoids from laboratories in Asia (e.g. China) or other countries that offer cheap raw materials,

Conclusion

This article focuses at all available data regarding the mode of action, the existing identification problems and the current worldwide legislation status of synthetic cannabinoids in “Spice” products.

Even though “Spice” products are commercialized only as incense for their rich aroma, the users utilize them exactly like cannabis by inhaling the smoke. “Spice” products are designed for youngsters that are willing to try cannabis but are afraid of the judicial consequences and/or the reputation

Conflict of interest statement

The authors declare that there are no conflicts of interest.

References (38)

  • D.R. Compton et al.

    Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents

    J. Pharmacol. Exp. Ther.

    (1992)
  • D.R. Compton et al.

    Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities

    J. Pharmacol. Exp. Ther.

    (1993)
  • V.S. Dalton et al.

    HU210-induced downregulation in cannabinoid cb1 receptor binding strongly correlates with body weight loss in the adult rat

    Neurochem. Res.

    (2009)
  • EMCDDA–Europol, 2008. Annual Report on the implementation of Council Decision...
  • EMCDDA, 2009a. Early-warning system. Understanding the ‘Spice’...
  • EMCDDA Poison Control Centre, Mainz, 2009b. Understanding the ‘Spice’ phenomenon. Via mass media and personal...
  • D.M. Fergusson et al.

    Cannabis and psychosis

    BMJ

    (2006)
  • T. Geller

    Cannabinoids: a secret history

    Chem. Herit. Newsmagazine

    (2007)
  • M. Glass et al.

    ‘Agonist selective regulation of G proteins by cannabinoid CB1 and CB2 receptors

    Mol. Pharmacol.

    (1999)
  • Cited by (292)

    View all citing articles on Scopus
    View full text