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NACB - Scientific Shorts (formerly NACB Blog)
By Donald L. Frederick, PhD, DABFT, FACB
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Although K2 has been known since 1856 as the second highest mountain (to Everest) in the Karakorum Range, more recently K2 has been known for another type of high;  the high that is achieved by smoking synthetic cannabinoids.  Although the origin of these compounds can be traced to synthetic products produced over the last 40 years, the recreational use (abuse) has been more recent with the first internet sales occurring some time around 2006.  The majority of marketing and sale has been around a series of products identified as “Spice”.  There were some seizures of compounds in Europe in 2007 with subsequent analysis and identification of the active compounds in 2008. 

Some of the first identifications were of synthetic cannabinoids that belong to a class of naphthoylindoles that were synthesized by J.W. Hoffman as cannabinoid receptor agonists.  These were given the series name of JWH-xxx with the most common identified as JWH-018. These compounds have a higher degree of binding to the CB-1 receptor causing these compounds to exert more psychological response per weight than marijuana.  The other series of compounds found were the HU-xxx series from Hebrew University with some of the series like HU-210 having 100 times the potency of THC.  The third set of compounds are of the class CP-xx,xxx based on cyclohexylphenol developed by Pfizer in the 1970’s.  From analysis of “Spice” samples from Europe the JWH series is more common.

Until recently these compounds were legal to possess and use.  The DEA on November 24, 2010 published intent to regulate many of these compounds.  Other countries have also placed these compounds under regulation. 

The toxicology of the Spice mixtures is complicated for several reasons.  The plant material that is used is not consistent from one batch to the next making evaluation of the toxicity difficult.  Some of the plant materials have some physiological effects by themselves. The more difficult evaluation is the toxicity of this new range of compounds that do not have any significant toxicology research.  Additionally the “Spice” product does not just contain one synthetic cannabinoid but usually several from different classes such as JWH-018 together with CP 47,497.  Recent reports that deaths have occurred from the use of “Spice” alone suggests that the toxicity may be greater than initially suspected.

Testing for the presence of these compounds is very difficult analytically for several reasons.  Since the compounds are very potent, they are found at low concentrations and very little is know about the metabolism of these compounds with most metabolites not being available to validate any testing method.  A second reason is that the compounds are continuing to change.  If the regulators put one compound under control the producers can modify the compound slightly and produce another synthetic compound that will be a CB1 agonist.  Some testing laboratories have taken a new approach by looking for a pattern of compounds present that would suggest the specimen contained an array of synthetic cannabinoid.  The analytical work is challenging and is in the early days.

 

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About the Author
Donald L. Frederick, PhD, DABFT, FACB
Donald L. Frederick, PhD, DABFT, FACB 
 

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References
Drug Enforcement Administration, Department of Justice. Schedules of controlled substances: temporary placement of five synthetic cannabinoids into schedule I.  Fed Regist 2010;75:71635-8.

European Monitoring Centre for Drug and Drug Addiction. www.emcdda.europa.eu (Accessed Jan 21, 2011).

Atwood BK, Huffman J, Straiker A, Mackie K. JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Brit J Pharmacol 2010;160: 585–93.

Davies S, Wood DM, Smith G, Button J, Ramsey J, Archer R, et al. Purchasing 'legal highs' on the Internet--is there consistency in what you get? QJM 2010;103:489–93.