The Spice You Don't Want in Your Life - A Professional Article Published in the March 2011 issue of "ASCLS Today"

  The toxicology department at the Seattle Division of VA Puget Sound Healthcare System has been fielding an increasing number of queries regarding the currently legal synthetic cannabinoid drug called “Spice,” also known as “K2.” Spice is a psychoactive chemical product marketed as an herbal smoking blend and as an “herbal potpourri” in the U.K.2 Due to the rise of its adverse side effects and its unique pharmacology, the drug is worthy of academic scrutiny.

  Spice first appeared in Europe in the 1990s, but did not impact American popular culture until midway through the first decade of the new millennium. The drug initially attracted attention when its users - usually teens - began falling ill post use. Side effects run the gamut from nausea, anxiety, and hallucinations to brain swelling3, sequela arising from an allergic reaction to the compound.

  Researchers, particularly in Germany where the drug is now banned, have discovered it to be comprised of a hodgepodge of herbs, plants and chemicals that together produce a cannabis-like high. Although the mixture does not contain any marijuana, it has shown to be a potent cannabimimetic that tests negative for tetrahydrocannabinol (THC) in traditional toxicology analyses.

  Several synthetic cannabinoids in particular are most often used in the mixture. One such compound is cannabicyclohexanol (C47,497).1 This drug is a cannabinoid receptor agonist developed by Pfizer in 19794 for research into the physiology of the endogenous cannabinoid signaling system at the molecular level during drug-receptor interaction.5 Other synthetic cannabinoids worth noting are JWH-018, JWH-073 and HU-210,1 all of which are currently legal in the U.S. as of this writing. Because of the current legal status of the ingredients used in the Spice mixture, many erroneously believe that Spice is a safe alternative to marijuana. However, this assumption could not be farther from the truth. In fact, a discussion of the pharmacology of JWH-018 in particular, will clearly prove this point.

  JWH-018 is a cannabinoid agonist, meaning that although it is not THC, it can still activate the cannabis receptors in the brain. Chemically, it is an aminoalkylindole derivative, versus THC which is a terpenoid compound produced by the Cannabis sativa plant.4 The two compounds are structurally unrelated to each other:

Structure of the Aminoalklyindole

Structure of THC

Structure of JWH-018

  
  Although there are multiple classes of structurally distinct cannabinoid agonist drugs, the amnioalkylindoles were the ones developed by Pfizer designed to target cannabinoid receptors to study drug-receptor physiology in research models as stated earlier. As illustrated, one can see the structure of JWH-018 is more similar to the aminoalkylindole structure than to that of THC. 
  At the heart of the production of the drug effect is the ability of the drug to bind to its specific receptor in the brain. Here, the target is the cannabinoid CB1 receptor. It is expressed widely throughout the brain and mediates the psychotropic effects of THC.

  Although only a few studies have examined the pharmacology of JWH-018 at the CB1 receptor, they have shown that JWH-018 is more potent than THC due to its ability to produce a physiological response at much lower concentrations. According to a 2000 paper in Drug and Alcohol Dependence by Huffman and Martin,7 JWH-018 binds to the CB1 receptor at nearly 4 times the potency of THC. This demonstrates the higher efficacy of JWH-018 than THC due to the production of higher maximal effects per dose.

  The December 2008 Journal of Mass Spectrometry compared the pharmacological properties of cannabinoids identified in synthetic cannabis, with THC.1 They noted that another synthetic cannabinoid - HU-210 is hundreds of times more potent than THC.6

  It is clear that synthetic cannabis is by no means a “safe” alternative to marijuana. It should also be clear that test systems need to be developed to analyze urine specimens for the metabolites of these synthetic cannabinoids. During the writing of this article, the author learned that a few reference laboratories are offering directed chromatographic testing for parent and/or metabolites. However, testing is still far from being standardized and therefore results should be interpreted with caution.9

  On November 24, 2010, the DEA notified the public through the Federal Register of its intent to temporarily control five synthetic cannabinoid chemicals found in so- called “fake pot” products such as K2 and Spice. Those chemicals are: JWH-018; JWH-073, JWH-200; CP-47,497 and cannabicyclohexanol; and CP-47,497 C8 homologue.

  The Controlled Substances Act requires the DEA to publish a Notice of Intent for at least 30 days before issuing a Final Order. Currently, DEA is working diligently to finalize that order which will place these five chemicals in Schedule I of the Controlled Substances Act for at least one year. DEA will publish the Final Order in the Federal Register that serves as the government’s official means for public notification.8 The Order may be published at any point in time so it is suggested interested parties continue to check the Federal Register on a regular basis at www.gpoaccess.gov/fr/.

1.  “Synthetic cannabis”. Wikipedia. Wikipedia Foundation, Inc. Web. 22 Jan.2011.


2.  Ford, Richard. “Spice ban as tests show lethal herbal drug is as potent as cannabis”. 

     Sunday Times.12 Aug. 2009. Print.

3.  McClain, Melissa. “Spice: A Dangerous New Drug”. Hubpages. N.P. n.d. Web. 16 Jan. 2011. 

4.  Dr. Leigh. “Cannaboid agonists and JWH-018-part 1”. The Path Forward. Wordpress. 
     Web. 6 June 2010. 

5.  Abel Pharmboy. “What’s the buzz? Synthetic marijuana, K2, Spice, JWK-018”. Terra 
     Sigillata. ScienceBlogs. Web. 9  Feb. 22010.

 6.  “Spice-Plant Material(s) Laced With Synthetic Cannabinoids or Cannabinoid Mimicking
       Compounds”. Microgram Bulletin. The Drug Enforcement Administration Office of 
       Forensic Sciences. Web. March 2009.

7.  Huffman, J.W. “Influence of the N-1 alkyl chain length of cannabimimetic indoles upon
     CB(1) and CB(2) receptor binding”. Drug and Alcohol Dependence. 60.2 (200) 133-40. Print.

8.  The United States Department of Justice. Drug Enforcement Administration. “Schedules of
     Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into 
     Schedule 1”. Federal Register. 24 Nov. 2010. 75.22671635-71638. Print. 

9.  Clinical and Forensic Toxicology News. “DEA Files Notice to Regulate ‘Spice’ Marijuana
     Substitutes”. Washington, DC. December 2010. Print.