THE EXPANDING REACH OF THE DESIGNERDRUG MOVEMENT IN 2011:CHALLENGES FOR FORENSICTOXICOLOGY & CHEMISTRYBarry K Logan PhD, D...
History and Context
Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKA...
Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKA...
Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKA...
Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKA...
Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKA...
Designer DrugsMid 2000’sNew tools for drug synthesisResearch Chemical Supply Industry2C-B, 2C-E, 2C-T-7AMT, DMT, 5-MeO-DiP...
Designer Drugs2008-2011Benzylpiperazines (6+)    BZP, TFMPP, m-CPPSynthetic Cannabinoids (200+)    JWH series, AM Series, ...
Legal Status
Legal StatusTitle 21 United States Code (USC) Controlled Substances ActSchedules drugs according to theirmedical use, liab...
Legal StatusSection 812. Schedule I (c) 17compounds including:3,4-methylenedioxyamphetamine3,4-methylenedioxymethampheta...
Legal StatusTemporary Scheduling3/1/2011 – Synthetic CannabinoidsJWH-018JWH-073JWH-200CP47,497 (C7)CP47,497 (C8)10/21...
Legal StatusFederal Analog Act (1986)The Federal Analogue Act defines ananalog as a substance which issubstantially simila...
Analogs? Yes!USA v Washam(2002) 312 F.3d 926, 930(i) 1,4-Butanediol and GHB are bothlinear compounds containing fourcarbon...
Analogs? No!USA v. Damon S. Forbes et al.(1992) 806 F.Supp. 232(i) AET is a primary amine while DMT    AETand DET are tert...
Synthetic Cannabinoids Update
Syn Canns Behavioral Effects
Syn Canns and Lethality
Syn Canns and Lethality
Syn Canns PrevalenceCalls to Poison Control Centers                                  NFLIS, Oct 2011
NMS Labs Blood Positivity Rates                         US DEA Controls                         JWH-018, 073, 200         ...
NMS Blood Positivity RatesAugust 2011-September 2011                    JWH-018       JWH-073       JWH-250      AM-2201  ...
Synn Cann Toxicity
Synn Cann Toxicity Young AC, Schwarz E, Medina G, Obafemi A, Feng SY, Kane C, Kleinschmidt K. Cardiotoxicity associated wi...
Bath Salts Update
Bath Salts and Depression
Bath Salts Toxicity
Bath Salts and Violence
Bath Salts and Violence
Cathinones/MDPV prevalenceCalls to Poison Control Centers                                  NFLIS, Oct 2011
Cathinones/MDPV prevalence                             NFLIS, Oct 2011
Mephedrone Toxicity
Mephedrone Toxicity
Bath Salts Toxicity
What to test for?
Designer Drug Scope 2009-2011Peters FT, Martinez-RamirezJA. Analytical toxicology ofemerging drugs of abuse.Ther Drug Moni...
Designer Drug Scope 2009-2011Wohlfarth A, Weinmann W.Bioanalysis of new designerdrugs. Bioanalysis. 2010May;2(5):965-79.
2011 Synthetic CannabinoidsJWH-007                        CP 47, 497 (C7)            HU-210JWH-015                        ...
Priority Analytical Targets    Designer Stimulants/Hallucinogens:   Federal Schedules:    Mephedrone,    MDPV, and Methy...
Priority Analytical Targets    Synthetic Cannabinoids:   Federal Schedules:    HU-210,   -211, JWH-018, -073, -200, CP47...
Priority Analytical Targets    Others:   2C-B-FLY, 2-Bromo-dragonfly   Tryptamines (5-MeO-DALT, 5-MeODiPT, AMT, DMT)   ...
Designer Drugs/Hallucinogens   Criminalistics Panel   Comprehensive Stimulants and Hallucinogens Panel, Test    (7210LI/...
Designer Drugs/Hallucinogens   Criminalistics Panel   Comprehensive Stimulants and Hallucinogens Panel, Test    (7210LI/...
Designer Drugs/Hallucinogens   Toxicology LCTOF Panel   Hallucinogens Screen - Expanded, Test (8755B/SP/U)
Designer Drugs/Hallucinogens   Toxicology LCMSMS Panel   Mephedrone & MDPV Stimulants Designer Drug Test,    (2623B/SP/U...
Choice of Matrix   Cathinones, Phenethylamines,    Tryptamines, Pyrovalerones   Blood/Urine – Parent Compound 10/100ng/m...
Screening   Immunoassay – Benzylpiperazines   Trazodone, meta-chlorophenylpiperazine (an    hallucinogenic drug and traz...
Analytical Technique   Immunoassay – Phenethylamines   Evaluation of commercial enzyme-linked immunosorbent    assays to...
Analytical Technique   Immunoassay – Synthetic Cannabinoids   NMS Labs data   No cross-reactivity of synthetic cannabin...
JWH-018/073 Urine ELISA   Immunoassay – Synthetic Cannabinoids   Synthetic Cannabinoid Metabolites Screen, Urine Test   ...
Synthetic Cannabinoids   Blood - Synthetic Cannabinoids   Synthetic Cannabinoids, Blood (Forensic) Test (9560B)        ...
Synthetic Cannabinoids   Urine - Synthetic Cannabinoids   Synthetic Cannabinoid Metabolites Screen - Expanded,    Urine ...
Analytical Technique   GCMS     Good candidate for parent compounds     Limited sensitivity in full scan     Most info...
Analytical Technique   LCMSMS     Superior sensitivity     Limited fragmentation     Shared transitions for close rela...
JWH-018 Metabolism                     NMS Labs, June 2011
JWH-018/073 Metabolism
Analytical Technique      High Resolution/LCTOF        Superior sensitivity        Molecular formula identification    ...
Summary   Rapidly changing market.   Regulation always a step behind the market.       Analog definitions will be fough...
ACKNOWLEDGEMENTSStaff of NMS Labs   Criminalistics   Toxicological Services   Research and Development Department   LC-MS/...
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The Expanding Reach of the Designer Drug Movement in 2011: Challenges for Forensic Toxicology & Chemistry

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This presentation considers the latest intelligence on what drugs are out in the U.S. grey market of products being sold as novelties, legal highs, “Bath Salts” and research chemicals, including an update on the latest trends in synthetic cannabinoid use and detection.

The proliferation of designer drugs in the last two years has made a remarkable change to the landscape of forensic toxicology and drug identification. The scope of compounds that require detection and measurement has grown from a few drugs that needed to be targeted in specific cases, to a wide range of esoteric compounds that arguably need to be included in general drug screens for forensic purposes. The growth continues as the industry that has built up around recreational drug manufacture adjusts in an attempt to stay one step ahead of the law.

The presentation reviews the general chemical drug classes encountered in forensic toxicology and chemistry casework, including mephedrone, methylone and MDPV, recently scheduled by the US DEA, and related the cathinones, 2C compounds, tryptamines, and pyrovalerones. This includes a survey of the latest published research, and a review of resources for analytical testing and standards.

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  • Hello and welcome to the third in our periodic series of web seminars, following on from previous ones featuring synthetic cannabinoids, and ?? Todays seminar is a review of whats going on in the designer drug market, focusing on the bath alts chemicals and also updating on trends in synthetic cannabinoids.
  • We’ll start with a brief tour of the designer drug phenomenon.
  • , CONGENERS, HOMOLOGUES AND ISOMERS,
  • By the mid to late 2000’s, with over 1bn people on the internet, specialty online retailers were selling both non-controlled psychoactive drugs and precursors for synthesis, Widespread audience, more difficult to find and control. Many of the initial compounds were taken from Shulgins book, especially the 2C series of psychedelic phenethylamines from Shulgin’s book PiHKAL, 2C-B, 2C-E, and 2CT7 but also a few tryptamines, AMT, DMT, and 5-MeODiPT (foxy methoxy). When a drug gained a sufficiently high prominence Federal Authorities have moved to place them in the Federal Schedule. Foxy, one of Shulgin’s received a lot of media attention in the early 2000’s and was added to schedule I in 2003, along with AMT. In 2004 Federal authorities executed operation web tryp, resulted in the arrests of 10 people. The DEA has followed a track of adding specific compounds to schedules
  • CP47,497 and DOM (2,5-Dimethoxy-4-methylamphetamine)
  • The Expanding Reach of the Designer Drug Movement in 2011: Challenges for Forensic Toxicology & Chemistry

    1. 1. THE EXPANDING REACH OF THE DESIGNERDRUG MOVEMENT IN 2011:CHALLENGES FOR FORENSICTOXICOLOGY & CHEMISTRYBarry K Logan PhD, DABFT,National Director Forensic Services, NMS LabsWillow Grove PA
    2. 2. History and Context
    3. 3. Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the InternetBeginnings of the “Research Chemicals”or “New Psychedelic” Movement.
    4. 4. Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the InternetBeginnings of the “Research Chemicals”or “New Psychedelic” Movement.
    5. 5. Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the InternetBeginnings of the “Research Chemicals”or “New Psychedelic” Movement.
    6. 6. Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the Internet 1995Beginnings of the “Research Chemicals”or “New Psychedelic” Movement.
    7. 7. Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the InternetBeginnings of the “Research Chemicals”or “New Psychedelic” Movement.
    8. 8. Designer DrugsMid 2000’sNew tools for drug synthesisResearch Chemical Supply Industry2C-B, 2C-E, 2C-T-7AMT, DMT, 5-MeO-DiPT2004 Operation Web TrypKhat, cathinone, methcathinone
    9. 9. Designer Drugs2008-2011Benzylpiperazines (6+) BZP, TFMPP, m-CPPSynthetic Cannabinoids (200+) JWH series, AM Series, RCS Seriesβ -Keto amphetamines (30+) Ephedrone, mephedrone, methylone, methedrone…Phenethylamines (2C suite) (15+) 2C-B, 2C-E, 2C-I, 2C-B, 2C-T-7,…Pyrrolidophenones (pyrovalerones) (20+) α-PVP, MDPV, PPP,…
    10. 10. Legal Status
    11. 11. Legal StatusTitle 21 United States Code (USC) Controlled Substances ActSchedules drugs according to theirmedical use, liability for addiction, andpotential for abuse. Schedule I includes:“…the following hallucinogenic substances, orwhich contains any of their salts, isomers, andsalts of isomers whenever the existence ofsuch salts, isomers, and salts of isomers ispossible within the specific chemicaldesignation.”
    12. 12. Legal StatusSection 812. Schedule I (c) 17compounds including:3,4-methylenedioxyamphetamine3,4-methylenedioxymethamphetamine5-methoxy-3,4-methylenedioxyamphetamine.3,4,5-trimethoxy amphetamineDiethyltryptamineDimethyltryptamine.4-methyl-2,5-diamethoxyamphetamine.
    13. 13. Legal StatusTemporary Scheduling3/1/2011 – Synthetic CannabinoidsJWH-018JWH-073JWH-200CP47,497 (C7)CP47,497 (C8)10/21/2011 “Bath Salts”MDPVMephedroneMethylone
    14. 14. Legal StatusFederal Analog Act (1986)The Federal Analogue Act defines ananalog as a substance which issubstantially similar to a scheduledsubstance and has either an effectsimilar to or greater than a controlled Mephedronesubstance or is thought to have such aneffect.21 U.S.C. § 813 Methcathinone
    15. 15. Analogs? Yes!USA v Washam(2002) 312 F.3d 926, 930(i) 1,4-Butanediol and GHB are bothlinear compounds containing fourcarbons and that there is only onedifference between the substances onone side of their molecules”, and (ii) that1,4-B is metabolized into GHB by thebody and so produces substantiallysimilar physiological effects.
    16. 16. Analogs? No!USA v. Damon S. Forbes et al.(1992) 806 F.Supp. 232(i) AET is a primary amine while DMT AETand DET are tertiary amines,(ii) AET cannot be synthesized fromeither DMT or DET, and(iii) the hallucinogenic or stimulant DMTeffects of AET are not substantiallysimilar to the effects of DMT or DET. DET
    17. 17. Synthetic Cannabinoids Update
    18. 18. Syn Canns Behavioral Effects
    19. 19. Syn Canns and Lethality
    20. 20. Syn Canns and Lethality
    21. 21. Syn Canns PrevalenceCalls to Poison Control Centers NFLIS, Oct 2011
    22. 22. NMS Labs Blood Positivity Rates US DEA Controls JWH-018, 073, 200 and CP,47,497
    23. 23. NMS Blood Positivity RatesAugust 2011-September 2011 JWH-018 JWH-073 JWH-250 AM-2201 RCS-4 Range (ng/mL) 0.10 – 26 0.93 – 1.7 0.11 – 6.5 0.13 – 10 0.25 – 1.8Mean ± SD (ng/mL) 2.98 ± 6.69 1.32 ± 0.54 1.12 ± 1.7 2.36 ± 2.97 0.72 ± 0.64 Median (ng/mL) 0.36 1.3 0.67 0.69 0.49 % Positive 12.3 1.6 10.7 27.0 4.1 JWH-019 JWH-081 JWH-122 JWH-210 RCS-8 % Positive 4.9 7.4 40.2 19.7 0.8 No positives for JWH-200, AM-694 Graf, Kacinko & Logan, SOFT, October, 2011
    24. 24. Synn Cann Toxicity
    25. 25. Synn Cann Toxicity Young AC, Schwarz E, Medina G, Obafemi A, Feng SY, Kane C, Kleinschmidt K. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med. 2011 Jul 28.
    26. 26. Bath Salts Update
    27. 27. Bath Salts and Depression
    28. 28. Bath Salts Toxicity
    29. 29. Bath Salts and Violence
    30. 30. Bath Salts and Violence
    31. 31. Cathinones/MDPV prevalenceCalls to Poison Control Centers NFLIS, Oct 2011
    32. 32. Cathinones/MDPV prevalence NFLIS, Oct 2011
    33. 33. Mephedrone Toxicity
    34. 34. Mephedrone Toxicity
    35. 35. Bath Salts Toxicity
    36. 36. What to test for?
    37. 37. Designer Drug Scope 2009-2011Peters FT, Martinez-RamirezJA. Analytical toxicology ofemerging drugs of abuse.Ther Drug Monit. 2010Oct;32(5):532-9.
    38. 38. Designer Drug Scope 2009-2011Wohlfarth A, Weinmann W.Bioanalysis of new designerdrugs. Bioanalysis. 2010May;2(5):965-79.
    39. 39. 2011 Synthetic CannabinoidsJWH-007 CP 47, 497 (C7) HU-210JWH-015 CP 47,497 (C8) HU-211JWH-018 CP 55,940 HU-308JWH-018 methyl hexyl homolog AM-694 HU-331JWH-019 AM-1220 JT-7770JWH-073 AM-1241JWH-073 methyl butyl homolog AM-2201JWH-081 AM-2233JWH-122 RCS-4JWH-133 RCS-8JWH-175 WIN 48,098 (Pravadoline)JWH-200 WIN 55,212-2JWH-201 WIN 55,212-3JWH-203 CB-25JWH-210 CB-52JWH-250JWH-251JWH-302JWH-398
    40. 40. Priority Analytical Targets Designer Stimulants/Hallucinogens: Federal Schedules: Mephedrone, MDPV, and Methylone State Schedule (PA) 4-Methoxymethcathinone 4-Fluoromethcathinone 3-Fluoromethcathinone  2C-C, 2C-D, 2C-E, 2C-H, 2C-I, 2C-N, 2C-P, 2C-T-2, 2C-T-4
    41. 41. Priority Analytical Targets Synthetic Cannabinoids: Federal Schedules: HU-210, -211, JWH-018, -073, -200, CP47,497 (C7), (C8) State Schedule JWH-019, JWH-250 Other JWH-120, -210, AM-2201, -694, RCS-4, - 8, JWH-081, WIN48,098
    42. 42. Priority Analytical Targets Others: 2C-B-FLY, 2-Bromo-dragonfly Tryptamines (5-MeO-DALT, 5-MeODiPT, AMT, DMT) Mitragynine (Kratom) Mesembrine/mesembrenol/hordenine (Kanna) Phenazepam Next: Aminoindanes, Benzofurans, Classical Hallucinogens Psilocin LSD Salvinorin A/B Dextromethorphan
    43. 43. Designer Drugs/Hallucinogens Criminalistics Panel Comprehensive Stimulants and Hallucinogens Panel, Test (7210LI/S) • 2,5-Dimethoxy-4-chloroamphetamine • 2,5-dimethoxy-4-iodophenethylamine • 2,5-dimethoxy-4-n-propylthiophenethylamine • 3, 4-methylenedioxyethamphetamine • 3,4-Methylenedioxyamphetamine • 3,4-Methylenedioxymethamphetamine • 3-Trifluoromethylphenylpiperazine • 4-Bromo-2,5-Dimethoxyphenethylamine • 4-fluoroamphetamine • 4-Fluorocathinone • 4-methyl-N-ethylcathinone • …
    44. 44. Designer Drugs/Hallucinogens Criminalistics Panel Comprehensive Stimulants and Hallucinogens Panel, Test (7210LI/S) • N-hydroxy-3,4-methylenedioxyamphetamine • para-Chlorophenylpiperazine • Pentylone • Phencyclidine • Psilocin • Salvinorin A • Scopolamine • THC • Thujone
    45. 45. Designer Drugs/Hallucinogens Toxicology LCTOF Panel Hallucinogens Screen - Expanded, Test (8755B/SP/U)
    46. 46. Designer Drugs/Hallucinogens Toxicology LCMSMS Panel Mephedrone & MDPV Stimulants Designer Drug Test, (2623B/SP/U) • Mephedrone • MDPV • Methylone (coming soon)
    47. 47. Choice of Matrix Cathinones, Phenethylamines, Tryptamines, Pyrovalerones Blood/Urine – Parent Compound 10/100ng/mL Salvia Blood/Urine – Salvinorin A/B 0.1ng/mL Synthetic Cannabinoids Blood – Parent Compound 0.1 – 50ng/mL Urine – Metabolites 0.1 – 100ng/mL Lack of available reference materials Lack of labeled internal standards requires careful validation.
    48. 48. Screening Immunoassay – Benzylpiperazines Trazodone, meta-chlorophenylpiperazine (an hallucinogenic drug and trazodone metabolite), and the hallucinogen trifluoromethylphenylpiperazine cross-react with the EMIT®II ecstasy immunoassay in urine. Logan BK, et al. J Anal Toxicol. 2010 Nov;34(9):587-9. Development of a Novel Benzylpiperazine ELISA Assay for Urine and Blood. Rodrigues* WC et al. SOFT/TIAFT 2011
    49. 49. Analytical Technique Immunoassay – Phenethylamines Evaluation of commercial enzyme-linked immunosorbent assays to identify psychedelic phenethylamines. Kerrigan S, et al. J Anal Toxicol. 2011;35(7):444-51.
    50. 50. Analytical Technique Immunoassay – Synthetic Cannabinoids NMS Labs data No cross-reactivity of synthetic cannabinoids or metabolites with Immunalysis Cannabinoids ELISA assay, or EMIT II Cannabinoids assay, at 10,000ng/mL Development of New Polyclonal Antibodies for the Screening of JWH Synthetic Cannabinoids and Metabolites Benchikh, ME et al. SOFT/TIAFT 2011
    51. 51. JWH-018/073 Urine ELISA Immunoassay – Synthetic Cannabinoids Synthetic Cannabinoid Metabolites Screen, Urine Test (9563U) September 20th, 2011 NMS Labs releases JWH-018 and JWH-073 ELISA.  Cross reacts with 4-OH-JWH-018, 5-OH-JWH-018, 4-OH- JWH-073, 4-OH-JWH-073  Does not cross react with THC-COOH Cutoff = 5 ng/mL
    52. 52. Synthetic Cannabinoids Blood - Synthetic Cannabinoids Synthetic Cannabinoids, Blood (Forensic) Test (9560B)  JWH-018  JWH-073  JWH-019  JWH-250  JWH-081  JWH-122  JWH-200  AM-2201  AM-694  RCS-4  RCS-8 RCS-4
    53. 53. Synthetic Cannabinoids Urine - Synthetic Cannabinoids Synthetic Cannabinoid Metabolites Screen - Expanded, Urine (Forensic) Test (9562U) JWH-018 N-(4-hydroxypentyl) metabolite O JWH-018 N-(5-hydroxypentyl) metabolite O JWH-019 N-(5-hydroxyhexyl) metabolite N JWH-073 N-(3-hydroxybutyl) metabolite OH JWH-073 N-(4-hydroxybutyl) metabolite JWH-250 N-(4-hydroxypentyl) metabolite* AM-2201 N-(4-hydroxypentyl) metabolite
    54. 54. Analytical Technique GCMS  Good candidate for parent compounds  Limited sensitivity in full scan  Most information for structural discrimination of closely related compounds.  Some synthetic cannabinoids and amphetamine compounds require derivatization. CP47,497 (C7) DOM
    55. 55. Analytical Technique LCMSMS  Superior sensitivity  Limited fragmentation  Shared transitions for close relatives  Requires separation in time/good chromatography 155 155 127 OH 127 OH N N O O OH 358 374 JWH-018 monohydroxy JWH-018 dihydroxy
    56. 56. JWH-018 Metabolism NMS Labs, June 2011
    57. 57. JWH-018/073 Metabolism
    58. 58. Analytical Technique  High Resolution/LCTOF  Superior sensitivity  Molecular formula identification  Many pairs of isobaric compounds exist  HU-210/HU-211  3-fluoromethcathinone/4-fluoromethcathinone  MDMA/3,4-BDB/p-MeO-MMA, etc  JWH-007/JWH-019  JWH-122/180  JWH-049/JWH-182Hudson et al. J Anal Toxicol. 2010 Jun;34(5):252-60.
    59. 59. Summary Rapidly changing market. Regulation always a step behind the market.  Analog definitions will be fought out in court. Growing evidence of adverse effects.  Violence, paranoia, psychosis, possible cardiotoxicity, and unexplained deaths. Laboratories should update their scope and keep it targeted to most prevalent compounds. LCMSMS/LCTOF are the most versatile techniques for detecting biomarkers. Innovative strategies required for identification of metabolites and acquisition of standards.
    60. 60. ACKNOWLEDGEMENTSStaff of NMS Labs Criminalistics Toxicological Services Research and Development Department LC-MS/MS Department QUESTIONS?

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