Testing for ‘Spice’ and Everything Nice

Andrew Stolbach, MD March 17, 2016 Objectives

List different classes of synthetic cannabinoids

Describe commercially available testing modalities for SC drugs

Discuss clinical and forensic uses of SC testing

Discuss limitations of clinical and forensic SC testing Recap

JWH-018, the naphthoylindole synthetic cannabinoid sweeps the world in 2008 Recap

United States Drug Laws were not adequate to address the epidemic

SC Drugs do not meet strict definition of controlled substance analogs

SC drugs were eventually scheduled on emergency, individual basis Cyclohexylphenol SC Structure

Core

Link Ring

Tail

Source : EMDCCA Naphthoylindole Naphthylmethylindole Phenylacetylindole Tetramethylcyclopropylindole Adamantylcarboximideindole Adamantylcarboximideindazole Quinolinoylcarboxylateindole Naming of SC Compounds

JWH Compounds named after J.W. Huffman Naming of SC Initials of Scientist

JWH AM- Compounds Compounds named after named after J.W. Alexander Huffman Makriyannis

JW Huffman Alexander Makriyannis Naming of SC Space Shuttle Mission STS-135 Naming of SC Japanese Girl Band AKB-48 Naming of SC Contraction of IUPAC Name

N-(1-adamantyl)-1-pentyl-1H- indazole-3-carboxamide

=

APINACA Non-comprehensive list of SC

5C-MN-24 (5-C-NNEI) ADB-FUBINACA FU-AEB JWH-249 PX-2 (5F-APP-PINACA) FUB-144 (FUB-UR-144) 5F-AB-PINACA ADB-PINACA JWH-250 PX-3 (APP-CHMINACA) FUB-AMB (AMB-FUBINACA) JWH-251 5F-ADB (5F-MDMB-PINACA) ADBICA (ADB-PICA) QUCHIC (BB-22) AM-1220 FUB-APINACA JWH-302 5F-AEB QUPIC (PB-22) AM-1221 FUB-PB-22 JWH-320 5F-AMB RCS-4 AM-1235 FUBIMINA (BIM-2201) JWH-398 5F-APINACA AM-1241 HU-210 JWH-424 RCS-8 5F-JWH-122 (MAM-2201, 4- AM-1248 HU-210 CAS LY-2183240 RCS-8 CAS Methyl-AM-2201) AM-2201 (5F-JWH-018) HU-308 CAS MAM-2201 SDB-005 5F-JWH-210 (EAM-2201, 4- AM-2232 JTE-907 MDA-19 SDB-006 Ethyl-AM-2201) AM-2233 JTE7-31 MDMB-CHMICA STS-135 (5F-APICA) 5F-MN-18 AM-630 (6- JWH-007 (wrongly advertised THJ-018 5F-MN-24 (5F-NNEI) Iodopravadoline) JWH-015 as MMB- CHMINACA) THJ-2201 5F-PCN AM-679 JWH -018 (AM-678) MDMB-CHMINACA UR-144 5F-QUPIC (5F-PB-22) AM-694 JWH-019 MDMB-FUBINACA WIN-48,098 (Pravadoline) 5F-SDB-005 AMB JWH-073 MEPIRAPIM APICA (SDB-001, 2NE1) JWH-081 WIN-55,225 (JWH-200) 5F-SDB-006 MMB-2201 (I-AMB, APINACA (AKB48) JWH-098 XLR-11 (5F-UR-144 CAS) 5F-UR-144 (XLR-11) 5F-AMB-PICA) APP-FUBINACA JWH-116 A-796,260 MN-18 AZ-037 JWH-122 (4-Ethyl-JWH-018) A-834,735 MN-24 (NNE1, BIM-018 JWH-149 A-836,339 NNEI) CB-13 JWH-167 MN-25 AB-001 CP 47,497 JWH-182 Nabilone AB-002 CP 55,940 JWH-193 NESS-0327 AB-005 CP-47,497 JWH-198 NESS-040C5 AB-CHFUPYCA CP-55,940 JWH-200 NM-2201 AB-CHMINACA (MA- EG-018 JWH-200 (WIN-55,225) Org-28611 CHMINACA) FAB-144 JWH-203 Pravadoline (WIN- AB-FUBINACA FDU-PB-22 JWH-210 (4-Methyl-JWH-018) 48,098) AB-PINACA PX-1 (5F-APP-PICA) ADB-CHMINACA (MAB- CHMINACA) Do we test for synthetic cannabinoids? It depends on who you are and which synthetic cannabinoids you are referring to Why We Test

Employment-based programs Reasonable suspicion Random Pre-employment Post-accident

Legal/Forensic/Postmortem Testing

Medical Settings Emergency departments Inpatient medical and psychiatry units Pain management programs Substance abuse treatment programs Department of Transportation Testing

Marijuana Cocaine Opiate Amphetamines Phencyclidine metabolites metabolites metabolites (PCP)

DOT Rule 49 CFR Part 40 Section 40.85 Department of Defense Testing

Marijuana metabolites Cocaine metabolites Amphetamines Opiate metabolites Phencyclidine (PCP) Semi-synthetic opioids Benzodiazepines Synthetic cannabinoids

Department of Defense Drug Demand Reduction Program Synthetic Cannabinoid Evolution

2010 2011 2012 2013 2014 JWH-018 AM-2201 JWH-203 PB-22 AB-PINACA JWH-073 AM-694 JWH-022 F-PB-22 AB-FUBINACA JWH-019 JWH-081 JWH-018 Cl-analog BB-22 ADBICA JWH-250 JWH-122 UR-144 MAM-2201 5-F-ADBICA JWH-200 XLR-11 AKB-48 ADB-PINACA JWH-210 AM-2233 F-AKB-48 ADB-FUBINACA RCS-4 AM-1248 5-F-ADB-PINACA RCS-8 A-796260 AB-001 F-AB-001/STR135 APICA PB-22 APINACA/AKB48 EAM-2201 THJ-2201 THJ-018 …

Dr. Barry Logan. NMS Labs Positivity – Blood: 2010-2013

Any Analyte 60 Feb 2011: April 2013: JWH-018 NMS BloodJuly 2012: Results US DEA US DEA JWH-073 US DEA JWH-250 Controls Controls XLR- controls JWH-019 JWH-018, 11 and UR- AM-2201, AM-2201 JWH-250 144 JWH-081 45 JWH-122 JWH-122 JWH-210 RCS-4 RCS-8 AM-2233 JWH-022 30 JWH-018 Analog UR-144

% Positive XLR-11

15

0 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 2010 2011 2011 2011 2011 2012 2012 2012 2012 2013 2013 2013 2013 2014

Source: Data extracted from NMS Labs Laboratory Information Management System . October 2010 March 2014.

Dr. Barry Logan. NMS Labs Positivity – Blood: 2014-2015

June 2015 Feb 2014: ADB- Dec 2014: CHMINACA US DEA US DEA Controls Controls added to AB-CHMINACA scope PB-22 AB-PINACA 5F-PB-22 THJ-2201 AB- FUBINACA ADB-PINACA

Dr. Barry Logan. NMS Labs Staying Current with Synthetic Cannabinoids

Seized drug casework Toxicological Casework Government Data/NFLIS Electronic Databases and Subscriptions Peer review literature monitoring Conference proceedings Collaborations with instrument vendors Drug Scheduling actions International conferences and networking Drug user forums, chat rooms and events Field Work Lab work

Dr. Barry Logan. NMS Labs Staying Current with SC National Forensic Laboratory Information System

DEA Program

Collects data from state, local, federal forensic labs

271 Labs throughout the US regularly report data NFLIS Report 2010-13 Immunoassay-Advantages +

Sensitive Readily automated

Inexpensive Immunoassay-Limitations -

Class specific Cross-reactivity is unpredictable Small changes- (length of tail, steric profile of functional group) affect cross-reactivity of the drug Immunoassay may take 9-18 months to develop Different matrices will require different targets Liquid Chromatography/Mass Spectrometry

Does not require Can be updated Definitive development of an validated in a new antibodies few days Blood/Serum-Advantages +

Quantitative Good for levels may be identifying recent clinically use meaningful Blood/Serum-Limitations -

Predominantly Requires targets parent venipuncture compounds Smoked Synthetic Cannabinoids Concentration Urine-Advantages +

Less invasive Easier to collect than than venipuncture venipuncture Urine-Limitations -

Identifies metabolites- not Substitution parent and compounds (so adulteration you need to know the metabolites Oral Fluid-Advantages +

Parent Easy- Indicates recent compound Noninvasive use detectable Oral Fluid-Limitations -

Does not indicate chronic use Oral Fluid Collection

Expectoration (neat oral fluid) Collection device Cotton collection pads/swabs Cellulose pads Oral Fluid Positivity for JWH-018 and JWH-200

Limit of detection

Limit of detection

Kneisel S et al. Annals Biochem Hair-Advantages +

Provides history of exposure (for Easy- example in child Noninvasive custody or reinstatement of driver’s license) Hair-Limitation

Vulnerable to sidestream contamination Commercial Tests-NMS Labs

5F-PB-22 ABCHMINACA AB-FUBINACA AB-PINACA ADB-PINACA ADB-PINACA ADBICA AKB48 BB-22 JWH-018 JWH-073 UR-144 (All metabolites)

NMS Labs, Synthetic Cannabinoid Metabolites Screen- Expanded, Urine (forensic) Commercial Tests-Quest

AM--2201 JWH-018 JWH-073 JWH-019 JWH-250

(all metabolites)

Quest Synthetic Cannabinoid Panel 2, Urine, LC/MS/MS Commercial Tests- ELISA Point of Care (Dipsticks)

Can be purchased Often limited online panels How good are these tests?

Detection False Sensitivity? Specificity? Interval Positives? Conclusions

SC use is Rapidly Evolving

We can accurately test for SC in urine, blood, hair, oral fluid

We can identify SC shortly after use (oral fluid, blood/serum) and months after use (hair)

Testing will not be accurate if we do not test for the drugs our patients are using