zombie-drugsIs synthetic or modern marijuana really just a cousin to the marijuana of yesterday? While they bind to the same endocannabinoid (CB) receptor, the similarity ends there. Despite these misnomers, synthetic cannabinoids are not directly related to marijuana. Their chemical structures are different. Yet, the implied promise that synthetic marijuana produces stronger results  has made synthetic cannabinoids popular with those experimenting with drug use. However, the reality of these super potent drugs of abuse includes unknown toxins and side-effects such as severe agitation, anxiety, nausea, vomiting, muscle spasms, intense hallucinations and psychotic episodes, and perhaps zombie-like behavior. Several forensic cases in Auckland, New York, and Los Angeles involving overdoses of synthetic cannabinoids in 2016 had first responders describe victims in an altered mental state that included a blank stare, slow response and zombie-like groaning.

Synthetic cannabinoids are the fastest growing class of novel psychoactive substances (NPS), with more than 200 versions introduced since 2008. According to the European Drug Monitoring Center, 1.6 tons of synthetic cannabinoids were seized in 2013, making these drugs among the most in-demand drugs of abuse. As forensic drug testing labs continue to identify and regulate new synthetic cannabinoids, limitations arise that make it increasingly challenging to detect new compounds, allowing these drugs to evade law enforcement.

Synthetic cannabinoids started out as pharmaceutical research drugs, discovered in the early 1990s when John W. Huffman began searching for new analgesics. One of the original compounds, JWH-018, is not structurally related to plant-based delta-9 tetrahydrocannabinol (THC), however it’s five times more potent for the CB1 receptor, with active metabolites that remain in the brain longer. Clandestine chemists hijacked Huffman’s published work and used his recipes for their own gains. They began selling “Spice” or “K2” plant material laced with JWH-018 and other active compounds, and used packaging labeled “Not for Human Consumption” to avoid oversight. Many of these drugs are full agonists with greater affinity for CB1, compared to THC (a partial agonist). For example, MAB Chminaca is five to 10 times more potent. The difficulty for law enforcement is that as soon as a synthetic cannabinoid is identified by crime labs and outlawed by the authorities, illicit drug makers are quick to synthesize a new one to take its place. Some newer analogues have an exponential increase in potency — AMB Fubinaca is 85 time stronger than THC and is associated with those zombie-like behaviors.

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These drugs have also been evolving with increased diversity in terms of chemical structures. Sub-classes of synthetic cannabinoids function similarly, but may not be structurally related. Whereas, derivatives within a sub-class may have very subtle modifications and share similar or identical isomeric structures. Targeted screening and confirmation for known synthetic cannabinoids is performed primarily with tandem mass spectrometry (MS/MS). MS technology has evolved, as well, providing exceptional specificity and highly precise mass accuracy (up to 5 decimal places), making it easier to reliably detect and identify drugs from various and related structural classes. Instruments such as the Q Exactive™ Focus Hybrid Quadrupole-Orbitrap™ mass spectrometer provide ultra-high resolution and accurate mass performance for analyzing “Spice” in urine.

As the list of synthetic cannabinoids and other NPS grows, open-untargeted screening for a wide variety of drugs becomes increasingly important. Identifying fast-evolving, new drugs is increasingly performed with high resolution accurate mass (HRAM) MS, in large drug testing panels. Screening with HRAM allows identification of both known and unknown drugs, and confirms identity, all within the same method. Technology such as Thermo Scientific™ Orbitrap™ mass spectrometry enables forensic drug testing labs to find tomorrow’s drugs today, streamline workflows, and keep pace with evolving synthetic cannabinoids.

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