“Mass Spectrometry-Based Approaches for Targeted and Broad Spectrum Detection and Identification of Synthetic Cannabinoids and other Designer Drugs of Abuse” by Dr. Thomas Brian

“Mass Spectrometry-Based Approaches for Targeted and Broad Spectrum Detection and Identification of Synthetic Cannabinoids and other Designer Drugs of Abuse," by Dr. Thomas Brian of RTI International.

Dr. Thomas is the Director of Analytical Chemistry and Pharmaceutics at RTI International. He received his B.A. in Biology from Kenyon College and his Ph.D. in Pharmacology from Virginia Commonwealth University. In 2012, Dr. Thomas received RTI's President's Award for his contributions in the fields of  Pharmacology, Analytical and Medicinal Chemistry, and Mass Spectrometry.Currently, he serves as the principal investigator for two contracts sponsored by the National Institute on Drug Abuse.

Dr. Thomas began his seminar by introducing Cannabinoids, which are any compounds that include cannabinol and other active substituents of Cannabis. Unlike the well-known Cannabis Sativa, which produces Delta-9 THC through pyrolysis (high temperatures associated with smoking), these chemical derivatives are produced synthetically in labs around the world. Although they usually carry a negative connotation, the FDA and DEA currently recognize several synthesized cannabinoids as having medicinal values. These include products such as, Marinol (dronabinol), which is an appetite stimulant, and Sativex (nabiximols), which is a spray used to treat spasticity.

The next topic discussed was "Spice," which is a common term used to describe a wide variety of herbal mixtures that produce similar experiences to cannabis and are marketed as "legal" and "safe" alternatives. Examples of such products include, K2, Kush, Ultra Cloud 10, and Mr. Nice Guy. Until recently, these products were widely available throughout the United States and had no regulations except those put in place by the distributors and/or sellers. Dr. Thomas emphasized the ease with which he was able to purchase these products in the Raleigh/Durham area for his own laboratory experiments.

Despite their similarities to the effects of traditional Cannabis, several major issues are associated with the use of Spice and other cannabinoids. According to a 2011 survey by Monitoring the Future of High School Students, 1 in 9 (~11.4%) high school students have used some form of synthetic cannabinoids. Furthermore, the American Association of Poison Control Centers reported that cases involving exposure to synthetic marijuana rose from 2,906 in 2010 to over 7,000 in 2011. These numbers are stunning considering the side-effects of cannabinoid usage is still unknown.

The pharmacology of cannabinoids was also discussed in detail by Dr. Thomas. He introduced the three branches of cannabinoids:

1. Photocannabinoids - Produced from Cannabis Sativa
2. Endocannabinoids - Produced naturally in mammalian species. 
3. Synthetic Cannabinoids - Produced in laboratories around the world. 

Dr. Thomas also discussed the function of CB1 (Cannabinoid Receptor Type 1) and CB2 (Cannabinoid Receptor Type 2). CB1 and CB2 are G protein-coupled cannabinoid receptors. Through 3H-CP-55,940 Autoradiography and other radioligands, he was able to track their pathways throughout the body: CB1 was found mainly in the Central Nervous System, while both CB1 and CB2 were discovered in the Periphery Nervous System. Additionally, he found that CB1 Receptor affinity of cannabinoid agonists correlated with pharmacological potency. Cannabinoids such as CP-55,940, WIN-55,212-2, and JWH-018 are full agonists at the CB1 Receptor whereas traditional THC is a weak partial agonist. In summary, synthesized cannabinoids activate receptors much greater than THC.

The two main problems associated with cannabinoids were introduced by Dr. Thomas in a section titled, "Spice - Pharmacology/Toxicology." First, unlike the THC associated with ingesting Cannabis, cannabinoids cannot be detected through Urinalysis. This realization poses problems to both Law Enforcement Agencies during criminal trials and the Medical Field during medical emergencies. From a medical point of view, synthesized cannabinoids present a major health risks. They have been reported to cause tachycardia, hypertension, low body temperature, psychological effects (prolonged and more intense than those caused by THC), and suicide. Additionally, in 2012, it was reported that XRL-11 and UR-144 caused immediate kidney failure in 12 cases. However, physicians neither have a way of testing for the presence of synthesized cannabinoids in their patients nor do they have a way of preventing/counteracting their effects.

From a Law Enforcement standpoint, cannabinoids are particularly difficult to assess because traditional methods of testing are not sophisticated enough to detect such chemicals. Test results for urinalysis show up negative and canines cannot be used to discover cannabinoids, which makes their use more prevalent. More advanced techniques can lead to the discovery and prosecution of cannabinoid users, however they are very expensive. Dr. Thomas listed the three most promising technologies:

1. Direct Analysis in Real Time Time-of-Flight Mass Spectrometry (DART-TOF)
2. Solid Phase Micro Extraction, Gas Chromatography/Mass Spectrometry (SPME GC/MS)
3. Ultra Performance Liquid Chromatography/Quadrupole Orthogonal Time-of-Flight        (UPLC/qTOF with AMF/MDF)

Of these three techniques, the most successful at detecting and accurately identifying individual cannabinoids was UPLC/qTOF.

The last portion of Dr. Thomas' seminar was geared toward discussing the future of cannabinoids in the United States. Although many cannabinoids are no longer displayed in stores, they are still able to be purchased legally over the internet. Furthermore, these products can be used without consequence, with the exception of 5 specific synthetic cannabinoids that have been banned by the DEA (there are currently over 180 known and identified cannabinoid molecules). 

The reason that so few cannabinoids have been banned in the United States is due to a court case that took place in Florida several years ago. As law makers passed stricter synthetic marijuana laws in states such as South Carolina and Georgia, cannabinoid producers and sellers began moving south. Eventually, the DEA decided to seek prosecution and arrested some of the largest cannabinoid producers in Florida. Immediately, companies sued on the basis that the DEA was inhibiting their ability to conduct business and the prosecution of cannabinoid producers was stalled for nearly 6 months.

When the cases finally came to trial, the defendants hired a group of 8 world-renowned scientists to investigate the allegations by the DEA. Specifically, the two cannabinoids in question were XLR-11 and UR-144. After several weeks of investigation, it was determined that the molecules of XLR-11 and UR-144 produced by the DEA were not identical to those found in the products of the defendants and the court case was dismissed. As a result, the DEA and other Law Enforcement Agencies are seeking to use the Controlled Substance Analog Act to prosecute cannabinoid producers and sellers. This Act would allow for the DEA to make arrests based on any molecule that is "similar" in conformation to any of the banned cannabinoids. However, this action is being countered by the constant production of new cannabinoids. As such, the proverbial game of cat and mouse continues...