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Testing for 'Spice' and Everything Nice

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Testing for 'Spice' and Everything Nice 3/17/2016 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 1 3/17/2016 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 2 3/17/2016 Naphthoylindole Naphthylmethylindole Phenylacetylindole 3 3/17/2016 Tetramethylcyclopropylindole Adamantylcarboximideindole Adamantylcarboximideindazole 4 3/17/2016 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 5 3/17/2016 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 6 3/17/2016 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 7 3/17/2016 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 8 3/17/2016 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 Blood ResultsJuly 2012: 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-081 45 JWH-250 144 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 9 3/17/2016 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 10 3/17/2016 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 11 3/17/2016 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 12 3/17/2016 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 13 3/17/2016 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 14 3/17/2016 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) 15 3/17/2016 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? 16 3/17/2016 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) Testingwillnotbeaccurateifwedonottestforthedrugsour patients are using 17.
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