Prevalence of Synthetic Cannabinoids in the Workplace

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Prevalence of Synthetic Cannabinoids in the Workplace David J. Kuntz, PhD, DABFT Executive Director of Analytical Toxicology Clinical Reference Laboratory Lenexa, KS 66215 email kuntzd@crlcorp.com 1

Webinar Objectives 1. Brief history of the emergence synthetic cannabinoids 2. Effects of synthetic cannabinoids on the body 3. Testing for synthetic cannabinoids at CRL 4. Results of testing 90,000 workplace samples 5. Governmental steps to control their distribution 2

Spice History The synthetic cannabinoids were created by Dr. John W. Huffman in 1995 who was synthesizing chemicals to imitate THC on CB1 (brain) & CB2 (immune system) receptors to develop new medicines. Other pharmaceutical companies and scientists have also been involved in research and has led to some of the other unique alpha-numeric naming conventions. One compound was the 18 th compound created and became JWH-018. The list of compounds numbered to 450. JWH-018 and JWH-073 became the most popular as they had high potency but have been largely replaced with different compounds. 3

Cannabinoid Receptor Effects Reported as useful in the treatment of pain, vomiting, epilepsy, multiple sclerosis, Parkinson s, anxiety, and other claims CB1 receptors when stimulated in the CNS results in the mood changes, memory, time perception, auditory and visual changes with increasing dose CB2 receptorsare mainly located in immune-cells and are responsible in reducing inflammation Toxic effects with increasing dose to include seizures, psychosis, tachycardia, hyperactivity and suicidal thoughts 4

Spice Effects Reported in Humans Psychological Physiological D O S E Mild euphoria Hyperventilation Hyperactivity Anxiety Paranoia Hallucinations Vomiting Seizures Suicidal Slurred speech Poor coordination Light-headedness Red eyes Pupil dilation Elevated Pulse/BP Flank pain (kidney injury) Chest pain 5

Packaging of Spice The synthetic cannabinoids are either liquids or crystalline which are dissolved in a solvent sprayed onto or mixed with potpourri of different fragrances and is often reflected in the name of the product. The packaging is typically plastic bags or small packet with very unique pictures and names. The internet is filled with purchase sites along with purchase prices by the gram or kilogram. All are labeled Not for Human Consumption as an attempt to eliminate the FDA/DEA from investigating the product. 6

Synthetic Cannabinoid Products 7

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Spice Testing at CRL The synthetic cannabinoids quickly became a popular alternative to plant marijuana due to its similar psychological and physiological effects. The use appeared to be widespread in the Midwest of the United States with a major supplier only 30 miles from Kansas City Clients of Clinical Reference Laboratory (CRL) were requesting that a workplace drug testing panel be developed to detect the use of these compounds by their employees In July 2011, the first panel of JWH-018 and JWH-073 was developed to detect use. The panel was expanded several times to now include twelve compounds. Screening is performed by LC/MS/MS with a separate LC/MS/MS analysis for confirmation using a different type of analytical column. Panel expansion/updates are based on the reported prevalence of new compounds and availability of the reference standards. 9

Synthetic Cannabinoids Generic terms to the herbal mixtures (incense, potpourri) which are sprayed with synthetic cannabinoids dissolved in acetone and smoked to get a legal high similar to marijuana. Typically packaged in foil-type packets and sold as Not for Human Consumption. Sold in convenience stores, gas stations, or head shops. CRL is currently testing for metabolites of the following 21-compounds: JWH-018 JWH-019 BB-22 JWH-073 JWH-081 PB-22 JWH-122 JWH-210 5-F-PB-22 JWH-250 AM-2201 AB-PINACA UR-144 MAM-2201 ADB-PINACA XLR-11 RCS-4 5-F-AB-PINACA AKB-48 5-F-AKB-48 ADBICA 10

Compound Similarities Many compounds have minor modifications that can enhance their pharmacologic effects by adding a Fluorine to the molecule Examples of modifications: AM-2201 is 5-fluoro-JWH-018 (10-fold stronger than JWH-018) XLR-11 is 5-F-UR-144 AB-PINACA vs. 5-F-AB-PINACA 11

Synthetic Cannabinoid Products K2 K2 Blond K2 Blue K2 Blueberry K2 Cherry K2 Citron K2 Cloud 9 K2 Melon K2 Pink K2 Rasta K2 Sex K2 Summit K2 Ultra K2 Watermelon K3 K3 Ultimate Lava Red Mr. Happy Armageddon Astral Blast Black Mamba Blue Fire Bonzai Cloud 10 Coma Demon Ritual Botanical Fake Weed Funky Green Stuff Genie Head Trip Herbal Incense Smoke Super Kush Texas Kush Voodoo Spice Zombie Twilight 12

Year One Data Summary (July 2011-September 2012) Total Number of Samples 15,995 Total Number of Positives 1,116 Overall Positive Rate - 7.0% 13

Year Two Data Summary (October 2012- September 2013) Total Number of Samples 40,857 Total Number of Positives 886 Overall Positive Rate 2.2% 14

Cumulative Data Summary (July 2011 April 2014) Total Number of Samples 89,051 Total Number of Positives 2630 Overall Positive Rate 2.9% 15

Jan 2013 Feb 2013 Mar 2013 Apr 2013 May 2013 Jun 2013 Jul 2013 Aug 2013 Sep 2013 Oct 2013 Nov 2013 Dec 2013 Jan 2014 Feb May2 2014 014 Apr 2014 Total Positive Samples 19 5 156 207 136 97 62 60 42 93 83 38 72 84 79 169 JWH-018 11 5 35 19 22 5 6 7 4 10 17 0 7 5 6 6 JWH-073 10 0 13 1 10 2 2 6 1 5 10 0 2 1 5 2 JWH-081 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 JWH-210 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 JWH-250 1 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 RCS-4 0 0 0 3 1 0 0 0 0 0 0 0 0 0 0 0 JWH-122 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 AM2201 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 JWH-019 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 MAM2201 0 0 2 0 0 0 0 1 0 0 0 0 2 0 2 1 UR-144 0 0 131 193 135 95 60 55 39 87 72 38 58 74 74 145 XLR11 0 0 21 30 1 2 1 1 0 2 0 1 0 2 1 5 AKB48 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 0 2 1 5-F-AKB48 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 0 0 0 0 BB-22 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 0 0 0 0 PB-22 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 13 10 6 34 5-F-PB n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 8 14 7 14 AB-PINACA n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 24 ADB-PINACA n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 0 5-F-AB-PINACA n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 5 ADBICA n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 0 16

9.0% Percent Positive by Reason for Testing 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Follow Up Not Specified Other Post Accident July 2012 thru June 2013 July 2013 thru April 2014 Preemployment Random Reasonable Cause Return to Duty 17

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K2 Positives K2 vs. Multi-drug Positive Jan 2013 -Apr 2014 THC AMP/MAMP K2 86.9% THC 5.6% AMP/MAMP 2.4% Methadone <1% HC/HM <1% COCAINE <1% BENZO <1% OC/OM <1% Morphine <1% Tramadol <1% BUTALBITAL <1% ETG <1% Bath Salts <1% 6-AM <1% Fentanyl <1% 19

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Requirements to Schedule New Chemicals The Comprehensive Crime Control Act of 1984 gives the Attorney General authority to emergency schedule a drug or drug class but must satisfy three of eight factors: 1. History and current pattern of use 2. Scope of abuse 3. Duration 4. Significance of abuse 5. Risk to public health 6. Actual abuse 7. Diversion from legitimate channels 8. Clandestine importation, manufacture or distribution 21

Synthetic Drug Control Act of 2012 Signed by President Obama in July 2012 Expanded wording to include cannabimimetic Agents Any substance that is a cannabinoid receptor Type I (CB1 receptor agonist as demonstrated by binding studies and function assays) Amends Schedule I of the Controlled Substances Act to include many additional Bath Salt compounds Expands time for temporary scheduling to avoid imminent hazards to Public Safety Extends from 1 to 2 years for emergency temporary scheduling Extends 6 month period to 12 months for additional information before a final ruling on status 22

What is the Future of Designer Drugs? As new synthetic cannabinoid products are identified, the government will be placing many of these into Schedule I status due to their health risks and abuse. Examples of new compounds on the horizon: AM1220 AM-694 AM-1235 AM-223 UR-597 EAM-2201 STS-135 BAY-38-7271 The labs will continue to develop new methods to look for hundreds of different known compounds covering multiple chemical families of structures. The future will be full of new chemicals that were never envisioned and the drug testing industry and legal review will be ongoing for many years to come. The penalties for the production must be very high to control their expansion since the profits are so very high. But with synthesis in overseas countries controlling their proliferation will be very hard. 23

Questions? 24