Synthetic CannabinoidThe popular nursery rhyme “What Are Little Boys Made Of?,” dating from the early 19th century, concluded that little girls, unlike little boys, were made of “sugar and spice and everything nice.” But, the subject of this post, synthetic cannabinoids called Spice and marketed as safe alternatives to cannabis, are not made of everything nice as the little girls referred to in the nursery rhyme.

While attending the ASCLD Annual Symposia for the forensic directors meeting, I found myself educating my DNA analysis colleague on how mass spectrometry helps solve crimes through various toxicology and drug substance laboratory tests. With teenage nieces and nephews, Amy was fascinated to hear about the complex market of synthetic drugs, and in particular, Spice.


History of Synthetic Cannabinoid

The discovery of synthetic cannabinoid compound family in the early 1990s occurred when John W. Huffman, (link to a fascinating interview by NPR), then a professor at Clemson University, began searching for new small molecule drug compounds that could be applied as new pharmaceutical analgesics. Of particular interest were those that bind to the cannabinoid brain (CB1) and peripheral (CB2) receptors, because the binding effects seemed to simulate the calming effect of cannabis.

It is believed that the modern retail Spice drug was started in Europe around 2004 by a small UK company. It has been viewed as an inexpensive legal substitution to marijuana. Often sold in legal retail outlets or via the internet as herbal incense or potpourri, the packaging is labeled Not for Human Consumption to avoid governmental oversight.

Over time local and federal municipalities have taken great lengths to remove many varieties from sale but due to the commercial appeal, garage chemists rapidly synthesize new analogues to avoid legal retribution thus making legality a moving target. Increasingly, new analogues are being added to the DEA Schedule 1 controlled substance list in the United States; putting them on par illegality as heroin and LSD.


Dangers of Synthetic Cannabinoid

Since the synthetic cannabinoid blends are not regulated, often homemade in small manufacturing plants with little or no quality control, and reformulated routinely, the effects are often unpredictable and, in some cases, deadly. The effects include severe agitation, anxiety, nausea, vomiting, tachycardia, elevated blood pressure, seizures and suicidal thoughts or actions. Why would anyone try this? – my first reaction too!

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Analytical Solutions for Synthetic Cannabinoid

Forensically, the need to analyze for synthetic substances happens when police are asked to intervene because someone is acting erratic or when death cases require investigation. Police officers are more frequently armed with portable narcotic analyzers (Thermo Scientific TruNarc Handheld Narcotics Analyzer) to presumptively test controlled compounds they find on site at a crime scene. Crime scene specialists then collect bulk drug substances for definitive structural and confirmatory testing back in their local or state forensic toxicology crime lab. Trained forensic scientists following SWGDRUG guidance use FT-IR spectrometers to perform structural screening and confirm those results most frequently using gas-phase mass spectrometry technology.

For cause of death investigations, coroners request forensic toxicology testing of autopsy samples for a standard list of compounds; more frequently using LC-MS triple quadrupole technology. However, because new analogues appear routinely, more laboratories following SWGTOX guidance are investing in high-resolution mass spectrometry (Thermo Scientific Q Exactive Focus Hybrid Quadrupole-Orbitrap MS) to design their lab of the future. Using this technology, forensic scientists can not only accurately screen and quantify their standard compound list but also retrospectively re-investigate the same data set for unknowns. Using new high resolution spectral libraries locally and updating them routinely via cloud-base applications, can reduce sample-to-answer time significantly.

With new legislation, more public awareness and better forensic investigative instrumentation, the National Institute on Drug Abuse reports a dramatic drop from 2012 to 2014 in teenagers using Spice. However, in a 2013 National Geographic documentary, titled, ‘Bath Salts,’ ‘Spice’ and US Military: Are Service Members Abusing Synthetic Drugs?, it’s clear there’s still work to be done before “everything is nice”.


Additional Resources

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Is identifying the list of ever-changing synthetic drugs a challenge to you or your laboratory? If so, I would like to hear your thoughts and experiences.