Barry K Logan PhD, DABFT Director of Forensic Services NMS Labs online Seminar September 16, 2010 K2 and the Synthetic Can...
K2 Phenomenon
K2 Phenomenon
K2 Phenomenon
K2 Phenomenon
K2 Phenomenon
K2 Phenomenon
K2 Phenomenon <ul><li>Origins of synthetic cannabinoid agonists. </li></ul><ul><li>Contents of various. commercial “K2” ty...
Marijuana Most popular recreational drug after alcohol and tobacco. Main psychoactive component THC #1 Drug in the DRE pro...
Synthetic Cannabinoids Synthetic drugs that mimic the effects of cannabis. Investigational use for appetite, blood pressur...
K2 Phenomenon Kansas,  Georgia, Kentucky,  Alabama,  Tennessee,  Louisiana, Missouri,  Hawaii,  Arkansas, Illinois  Missis...
Clemson Series - JWH JWH-018 JWH-073 JWH-250
Marijuana to Spice THC HU-210 CP 47,497 WIN 55,212
Cannabinoid Mechanism of Action Cerebral Cortex Higher Cognitive Function Basal Ganglia Cerebellum Movement Hippocampus Le...
Herbals - Botanical Substrate Glycyrrhiza glabra (Cultivated Liquorice)  Astragalus membranaceus (Milk Vetch) Verbascum th...
Synthetic Cannabinoids – Drug ID <ul><ul><li>Agilent 5973 Mass Spectrometer </li></ul></ul><ul><ul><li>Agilent 6890 Gas Ch...
Synthetic Cannabinoids – Drug ID JWH-018 JWH-073 JWH-200 HU-210/11 JWH-019 JWH-200 WIN 55,212 JWH-015 JWH-133 JWH-250 CP55...
K2 Blends - Drug Content (* Uchiyama et al, 2010) JWH-018 (mg/g) JWH-073 (mg/g) CP47,497 (n=8) (mg/g) JWH-250  (mg/g) K2 B...
Synthetic Cannabinoid Effects
Synthetic Cannabinoid Effects
Synthetic Cannabinoid Metabolism
Synthetic Cannabinoid Effects T. Sobolevsky, et al., Detection of JWH-018 metabolites in smoking mixture post-administrati...
Synthetic Cannabinoid Disposition
Synthetic Cannabinoids at NMS Labs <ul><li>Synthetic Cannabinoids in Blood - $195 </li></ul><ul><ul><li>LCMSMS  LOQ/LOQ  -...
NMS Labs Special Projects Matrix Analytes Blood Serum Oral Fluid (Refrigerate) Parent Compounds – JWH-018, JWH-073, JWH-20...
Missouri K2 Administration Study <ul><li>IRB Human subjects and ethical approval obtained by University of Central Missour...
Missouri K2 Administration Study <ul><li>Onset of effects in about 2-3 minutes </li></ul><ul><ul><li>Dry mouth </li></ul><...
Missouri K2 Administration Study <ul><li>Reported effects: </li></ul><ul><ul><li>Tachycardia (increased heart rate, 5-30mm...
K2 use and the DRE Matrix * High doses Drug Symptom Matrix                   CNS Depressant Inhalants Dissociative Drugs  ...
NMS Labs Blood JWH-018 and -073 L/L extraction JWH-073 d-9 Istd Quantitative  LOD/LOQ 0.1ng/mL Waters TQD Acquity Gradient...
NMS Labs Blood JWH-018 and -073
Missouri K2 Administration Study Subject BM Smoked “K2 Citron” 10mg/g JWH-018/073 0.3g in water pipe 3 inhalations over 30...
Synthetic Cannabinoid Disposition
Synthetic Cannabinoid Disposition * *
NMS Labs Urine JWH-018 and -073 L/L extraction Qualitative JWH-073 d-9 Istd Method 1: hydrolyzed – Waters TQD Mono and Di ...
NMS Labs Urine SC metabolites
Missouri K2 Administration Study Subject BM - Urine Time JWH-018 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15...
York County PA, DRE Case <ul><ul><li>Vehicle crashed into snowbank </li></ul></ul><ul><ul><li>Subject appeared drunk or hi...
York County PA, DRE Case <ul><ul><li>Pulse 96-88, BP 150/80 </li></ul></ul><ul><ul><li>Eyes watery, red, bloodshot, pupils...
York County PA, DRE Case <ul><ul><li>Drug Identification </li></ul></ul><ul><ul><ul><li>“ Space” contained JWH-018, traces...
Death Investigation Case <ul><ul><li>19 yo male out for a night of partying with friends. </li></ul></ul><ul><ul><li>Smoki...
Conclusions <ul><ul><li>Synthetic cannabinoids have great toxicological significance. </li></ul></ul><ul><ul><li>The range...
Acknowledgments <ul><ul><li>Analysis </li></ul></ul><ul><ul><ul><li>NMS Labs </li></ul></ul></ul><ul><ul><ul><ul><li>Allan...
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K2 and the Synthetic Cannabinoids: Pharmacology, Effects and Chemical Analysis

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Presented September 16, 2010 by Dr. Barry K. Logan, PhD, DABFT, NMS Labs National Director of Forensic Services

NMS Labs has responded to the recent explosive growth in popularity of synthetic cannabinoid agonists in so-called “herbal blends” by developing new tests for the active chemicals in botanical material, and most recently for the parent drugs and their metabolites in blood and urine. This presentation describes the history and origin of the chemicals of concern, the composition of the various commercial products containing them, their known pharmacology, and the documented effects on drivers, and human test subjects. We also review the adverse effects that have resulted in hospitalization, and even allegedly in deaths. This presentation describes the challenges around providing a chemical test for these new drugs, information on their stability in biological fluids, and the validation of quantitative methods for their determination.

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  • more credible reports are now appearing in the medical literature also.
  • Including acute intoxications, with anxiety, paranoia, gross impairment, and marked tachycardia.
  • Marijuana, the most popular recreational drug in the United states after alcohol is enjoying growing popularity and seeing increasing efforts for its legalization. Californians will decide on November second whether to pass a ballot initiative, proposition 19, to legalize MJ under CA but not federal law, and regulate and tax its trade and distribution. Meanwhile, MJ is the number 1 drug in the DRE program, some 25 million Americans have smoked it in the past year, and a recent national roadside drug test survey showed that 6.8% of Friday and Saturday evening drivers tested positive for its use.
  • Synthetic drugs that mimic the effects of cannabis through binding at the same receptors, principally the CB1 receptor, more of which about momentarily. The drugs were developed in the 1980’s and 1990’s as potential cannabinoid agonists that might possess some of the advantageous effects of cannabis, appetite stimulation, and anti- nausea properties, blood pressure, and much flaunted as adjuncts in cancer pain therapy, without the euphoric intoxicating effects for which the drug was popular recreationally. Now the drugs are sold widely on the internet and convenience stores and gas stations, smoke shops and head shops.
  • Other C1 agonists with very diverse structures have also been identified in these illicit materials, including HU-210, a true THC analog, first synthesized at Hebrew University if Jerusalem, where the structure of THC was first elucidated, and partial analogs the synthetic compounds CP47,497 (C7 and C8 homologs), first manufactured by Pfizer, and WIN 55,212 developed by Sterling Winthrop. Their diversity makes the outlawing of these compounds as analogs, very difficult. The comparative receptor binding strengths of these compounds have been evaluated but how this relates to their potency in-vivo is unknown. HU-210 for example has a binding potency several hundred times that of THC. This potency can clearly lead to challenges in detecting pharmacologically significant amounts. There are literally dozens of these compounds whose synthesis has been described, and clearly many other analogs that could be synthesized with minor modification to circumvent scheduling or other regulation. This presents a greater challenge for the future not just dealing with those drugs already on the market, but those in the wings as the regulated landscape changes.
  • Cannabinoids and their synthetic analogs can function as either agonists or antagonists at the CB1 and 2 receptors in the brain. The latter are mainly found in the immune system and in nerve terminals where their function is not well understood, but the major effects are in the CB1 receptor sites whose distribution in the brain correlates with areas involved in physiological, psychomotor and cognitive effects. Principally in the areas associated with cognitive function, movement, learning, memory and stress, appetite, pain perception, and nausea and vomiting. All factors that we associate with and are familiar with from the effects of THC. We will see later how the initial reports of the observed effects of these synthetics correlate with these expectations.
  • Teske and coworkers conducted self administration of a product containing JWH-018. They reported sickness, sedation and dry mouth, hot flushes, burning eyes, and thought disruption. No change in pupil size. But pulse and blood pressure were noticeably elevated.
  • They reported quantitative concentrations in in serum, with peak concentrations occurring in the range of 8-10 ng/mL within a few minutes of smoking, and concentrations falling below 1ng/mL within 3 hours. Trace concentrations were reported at 24 hours (&lt;0.1ng/mL)
  • Our findings show that there are major mono di and tri hydroxymetabolites present in the first urine samples collected within a hour of administration. The isomer shown are commercially available in the last two weeks, however none of the indole hydroxylated metabolites are major, the side chain OH is minor, and the major monohydroxy metabolite is hydroxylated in a position other than shown in the Sobolevsky paper. This is under investigation, and will be reported at the workshop at AAFS in Chicago in February at the K2 workshop. Dr John Huffman will be a guest speaker and it promises to be a lively presentation.
  • Because of the complex metabolic profile, the urine method has taken a lot longer to develop and validate than the blood method. The method has been validated however through the use of authenticated positive and negative urine samples. Two independent complementary methods have been developed to provide further certainty of identification – critical for forensic casework in the absence of authentic reference standards. We believe this level of detail distinguishes our assay from that of our competitors. Other aspects of the validation procedure, sensitivity, selectivity, PPV and NPV apply to the methods also. Stability at room temp, refrigerated and frozen have been assessed, as well as in the autosampler, and appears to be relatively stable, but as noted does stick to plastic, requiring very careful handing of controls and SRMs. Authentic pedigreed samples diluted to the detection threshold are used as controls, and the method requires the presence of the major mono and di hydroxymetabolites, with transition ratios in range and retention time matching in order to report positives. All screened positives are confirmed.
  • Here is an example of the LCMSMS data from method 1. Describe
  • K2 and the Synthetic Cannabinoids: Pharmacology, Effects and Chemical Analysis

    1. 1. Barry K Logan PhD, DABFT Director of Forensic Services NMS Labs online Seminar September 16, 2010 K2 and the Synthetic Cannabinoids: Pharmacology, Effects, and Chemical Analysis From the Premium Provider of Forensic Services
    2. 2. K2 Phenomenon
    3. 3. K2 Phenomenon
    4. 4. K2 Phenomenon
    5. 5. K2 Phenomenon
    6. 6. K2 Phenomenon
    7. 7. K2 Phenomenon
    8. 8. K2 Phenomenon <ul><li>Origins of synthetic cannabinoid agonists. </li></ul><ul><li>Contents of various. commercial “K2” type products. </li></ul><ul><li>Mechanism of Action and Pharmacology. </li></ul><ul><li>Analytical challenges. </li></ul><ul><li>Human pharmacodynamics. </li></ul><ul><li>A preview of the DUI environment. </li></ul>
    9. 9. Marijuana Most popular recreational drug after alcohol and tobacco. Main psychoactive component THC #1 Drug in the DRE program Some 25 million Americans have smoked marijuana in the past year, and more than 14 million do so regularly. Possession and use illegal under federal law, but states have variable policies on enforcement and prosecution. 6.8% of Friday and Saturday evening drivers test positive for use.
    10. 10. Synthetic Cannabinoids Synthetic drugs that mimic the effects of cannabis. Investigational use for appetite, blood pressure, nausea, etc First synthesized in the 1980’s Sprayed onto dried plant leaves, flowers and stems, and smoked. Legal or unregulated in most US states.
    11. 11. K2 Phenomenon Kansas, Georgia, Kentucky, Alabama, Tennessee, Louisiana, Missouri, Hawaii, Arkansas, Illinois Mississippi
    12. 12. Clemson Series - JWH JWH-018 JWH-073 JWH-250
    13. 13. Marijuana to Spice THC HU-210 CP 47,497 WIN 55,212
    14. 14. Cannabinoid Mechanism of Action Cerebral Cortex Higher Cognitive Function Basal Ganglia Cerebellum Movement Hippocampus Learning, Memory, Stress Hypothalamus Appetite Spinal Chord Pain, Peripheral sensation Medulla Nausea, Vomiting
    15. 15. Herbals - Botanical Substrate Glycyrrhiza glabra (Cultivated Liquorice) Astragalus membranaceus (Milk Vetch) Verbascum thapsus (Common Mullein) (Uchiyama et al, 2010)
    16. 16. Synthetic Cannabinoids – Drug ID <ul><ul><li>Agilent 5973 Mass Spectrometer </li></ul></ul><ul><ul><li>Agilent 6890 Gas Chromatograph </li></ul></ul><ul><ul><li>Electron Impact mode </li></ul></ul><ul><ul><li>Full scan </li></ul></ul><ul><ul><li>Total run time 10 minutes </li></ul></ul><ul><ul><li>Sensitivity 20-50 ug/g </li></ul></ul>
    17. 17. Synthetic Cannabinoids – Drug ID JWH-018 JWH-073 JWH-200 HU-210/11 JWH-019 JWH-200 WIN 55,212 JWH-015 JWH-133 JWH-250 CP55,940 CP 47,497 (n=7) CP 47,497 (n=8)
    18. 18. K2 Blends - Drug Content (* Uchiyama et al, 2010) JWH-018 (mg/g) JWH-073 (mg/g) CP47,497 (n=8) (mg/g) JWH-250 (mg/g) K2 Blonde 12 13 - - K2 Standard 9 9 - - K2 Citron 10 10 - - K2* (Unknown) - - 6 - K2 Summit 11 9 - - K2 Blue 15 - - - K2 Pink 11 - - - K2 Latte 16 0.28 - 14 K2 Mint 19 0.30 - - K2 Silver 8 - - 16 Spike Gold 20 11 - - Spike Maxx 17 - - 19 Spike Diamond 17 0.07 - - Spike Silver 9 16 - - Space 10 - - - Herbal blends* 2.0 – 35.9 - 1.1 – 16.9 -
    19. 19. Synthetic Cannabinoid Effects
    20. 20. Synthetic Cannabinoid Effects
    21. 21. Synthetic Cannabinoid Metabolism
    22. 22. Synthetic Cannabinoid Effects T. Sobolevsky, et al., Detection of JWH-018 metabolites in smoking mixture post-administration urine, Forensic Sci. Int. (2010), doi:10.1016/j.forsciint.2010.04.003
    23. 23. Synthetic Cannabinoid Disposition
    24. 24. Synthetic Cannabinoids at NMS Labs <ul><li>Synthetic Cannabinoids in Blood - $195 </li></ul><ul><ul><li>LCMSMS LOQ/LOQ - 0.1ng/mL </li></ul></ul><ul><ul><li>JWH-018, JWH-073 (screened, confirmed, quantitated). </li></ul></ul><ul><ul><li>JWH-018, JWH-073, JWH-019, JWH-250 (screened, confirmed) </li></ul></ul><ul><li>Synthetic Cannabinoids in Urine - $60 </li></ul><ul><ul><li>LCMSMS, LOD - 0.1ng/mL </li></ul></ul><ul><ul><li>JWH-018 mono-hydroxy and di-hydroxy metabolites (screened, confirmed) </li></ul></ul><ul><ul><li>JWH-018 tri-hydroxy metabolites (monitored) </li></ul></ul>
    25. 25. NMS Labs Special Projects Matrix Analytes Blood Serum Oral Fluid (Refrigerate) Parent Compounds – JWH-018, JWH-073, JWH-200, HU-210, HU-211, JWH-019, JWH-200 WIN 55,212, JWH-015, JWH-133, JWH-250, CP55,940, CP 47,497 (n=7) CP 47,497 (n=8) … Urine (Freeze) Ring monohydroxylated metabolites – glucuronidated Ring dihydroxylated metabolites – glucuronidated Desmethyl ring hydroxylated metabolites - glucuronidated
    26. 26. Missouri K2 Administration Study <ul><li>IRB Human subjects and ethical approval obtained by University of Central Missouri. </li></ul><ul><li>Six subjects smoked K2 Summit, Citron, or Standard </li></ul><ul><li>Each contained JWH-018, JWH-073, or CP47,497 </li></ul><ul><li>Subjects performed SFST’s, cognitive tests and DRE Exam. </li></ul><ul><li>Blood, urine and oral fluid collected. </li></ul>
    27. 27. Missouri K2 Administration Study <ul><li>Onset of effects in about 2-3 minutes </li></ul><ul><ul><li>Dry mouth </li></ul></ul><ul><ul><li>Light headedness </li></ul></ul><ul><ul><li>Blurred vision </li></ul></ul><ul><ul><li>Agitation, Motor restlessness </li></ul></ul><ul><ul><li>Time dilation </li></ul></ul><ul><li>DRE Exam </li></ul><ul><ul><li>Increased pulse and blood pressure </li></ul></ul><ul><ul><li>Lack of convergence </li></ul></ul><ul><ul><li>No HGN, or VGN </li></ul></ul><ul><ul><li>Pupils normal, muscle tone normal </li></ul></ul><ul><li>SFST’s </li></ul><ul><ul><li>3-4 inches of sway, leg body tremors </li></ul></ul><ul><ul><li>Loss of balance </li></ul></ul><ul><ul><li>Loss of motor coordination </li></ul></ul>
    28. 28. Missouri K2 Administration Study <ul><li>Reported effects: </li></ul><ul><ul><li>Tachycardia (increased heart rate, 5-30mm/Hg) </li></ul></ul><ul><ul><li>Dry Mouth </li></ul></ul><ul><ul><li>Felt Impaired, subjective thought disruption </li></ul></ul><ul><ul><li>Changes in perception </li></ul></ul><ul><ul><li>Impaired sense of time </li></ul></ul><ul><ul><li>Mild anxiety, paranoia </li></ul></ul><ul><ul><li>Sedation </li></ul></ul><ul><ul><li>Post-intoxication exhaustion </li></ul></ul>
    29. 29. K2 use and the DRE Matrix * High doses Drug Symptom Matrix                   CNS Depressant Inhalants Dissociative Drugs CNS Stimulants Hallucinogens Narcotic analgesics Cannabis K2                   Horizontal nystagmus Yes Yes Yes No No No No No Vertical Nystagmus Present * Present* Present No No No No No Lack of Convergence Present Present Present No No No Present Present Pupil Size Normal Normal Normal Dilated Dilated Constricted Dilated* Normal Reaction to Light Slow Slow Normal Slow Normal Little to none Normal Normal Pulse Rate Down Up Up Up Up Down Up Up Blood Pressure Down Up/Down Up Up Up Down Up Up Body Temperature Normal Up/Down/Normal up Up Up Down Normal Normal
    30. 30. NMS Labs Blood JWH-018 and -073 L/L extraction JWH-073 d-9 Istd Quantitative LOD/LOQ 0.1ng/mL Waters TQD Acquity Gradient 4 minute run Formic acid vs ACN 2 Transitions per analyte
    31. 31. NMS Labs Blood JWH-018 and -073
    32. 32. Missouri K2 Administration Study Subject BM Smoked “K2 Citron” 10mg/g JWH-018/073 0.3g in water pipe 3 inhalations over 30 minutes
    33. 33. Synthetic Cannabinoid Disposition
    34. 34. Synthetic Cannabinoid Disposition * *
    35. 35. NMS Labs Urine JWH-018 and -073 L/L extraction Qualitative JWH-073 d-9 Istd Method 1: hydrolyzed – Waters TQD Mono and Di hydroxy metabolites 2 transitions per analyte Method 2: unhydrolyzed – ABI 5000 Monohydroxy glucuronide – daughter – grandaughter 2 transitions per analyte and precursor
    36. 36. NMS Labs Urine SC metabolites
    37. 37. Missouri K2 Administration Study Subject BM - Urine Time JWH-018 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 +/- √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √ Time JWH-073 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 X √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √
    38. 38. York County PA, DRE Case <ul><ul><li>Vehicle crashed into snowbank </li></ul></ul><ul><ul><li>Subject appeared drunk or high, difficulty speaking, incoherent, mumbling, slow slurred speech, nonsense, giggling. </li></ul></ul><ul><ul><li>Had smoked “Space” less than 2 hours before. </li></ul></ul><ul><ul><li>“ I’m not a DUI. The stuff I smoked is legal. You can’t arrest me” </li></ul></ul><ul><ul><li>Courtesy Cpl Brian Torkar, PSP </li></ul></ul>
    39. 39. York County PA, DRE Case <ul><ul><li>Pulse 96-88, BP 150/80 </li></ul></ul><ul><ul><li>Eyes watery, red, bloodshot, pupils dilated </li></ul></ul><ul><ul><li>Eyelids droopy, HGN present, no VGN </li></ul></ul><ul><ul><li>Lack of convergence </li></ul></ul><ul><ul><li>SFST’s </li></ul></ul><ul><ul><ul><li>4 inches of sway on Romberg </li></ul></ul></ul><ul><ul><ul><li>Lost balance, used arms on WAT </li></ul></ul></ul><ul><ul><ul><li>Swayed, used arms on OLS </li></ul></ul></ul><ul><ul><ul><li>Poor finger to nose performance </li></ul></ul></ul><ul><ul><li>Courtesy Cpl Brian Torkar, PSP </li></ul></ul>
    40. 40. York County PA, DRE Case <ul><ul><li>Drug Identification </li></ul></ul><ul><ul><ul><li>“ Space” contained JWH-018, traces of JWH-200 </li></ul></ul></ul><ul><ul><li>Toxicology </li></ul></ul><ul><ul><ul><li>Blood collected approximately 4 hours after use. </li></ul></ul></ul><ul><ul><ul><li>Positive for diphenydramine <50ng/mL </li></ul></ul></ul><ul><ul><ul><li>0.2 ng/mL for JWH-018 by directed analysis, LC-TOF </li></ul></ul></ul>
    41. 41. Death Investigation Case <ul><ul><li>19 yo male out for a night of partying with friends. </li></ul></ul><ul><ul><li>Smoking marijuana and K2. </li></ul></ul><ul><ul><li>Becomes disoriented. </li></ul></ul><ul><ul><li>Returned home late in evening. </li></ul></ul><ul><ul><li>Found dead in bed the following morning. </li></ul></ul><ul><ul><li>No anatomic cause of death. </li></ul></ul><ul><ul><li>Toxicology (cardiac) </li></ul></ul><ul><ul><ul><li>Delta-9-carboxy THC 13ng/mL </li></ul></ul></ul><ul><ul><ul><li>JWH-018 0.71ng/mL </li></ul></ul></ul><ul><ul><li>Cause of Death – currently undetermined </li></ul></ul>
    42. 42. Conclusions <ul><ul><li>Synthetic cannabinoids have great toxicological significance. </li></ul></ul><ul><ul><li>The range of synthetics is likely to be a moving target. </li></ul></ul><ul><ul><li>Effect profile very similar to marijuana </li></ul></ul><ul><ul><li>Should be considered in “marijuana” cases where no THC or metabolites present. </li></ul></ul><ul><ul><li>Blood analysis should target parent drugs <1ng/mL </li></ul></ul><ul><ul><li>Urine analysis must look for multiple points of identification, as standards are unavailable. </li></ul></ul>
    43. 43. Acknowledgments <ul><ul><li>Analysis </li></ul></ul><ul><ul><ul><li>NMS Labs </li></ul></ul></ul><ul><ul><ul><ul><li>Allan Xu </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Matt McMullin </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lindsay Reinhold </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Donna Warrington </li></ul></ul></ul></ul><ul><ul><ul><li>Webinar </li></ul></ul></ul><ul><ul><ul><ul><li>Amanda Panepinto </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Julie Ruth </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sherri Kacinko </li></ul></ul></ul></ul><ul><ul><li>Dosing Study </li></ul></ul><ul><ul><ul><ul><li>Bob Welsh </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Tracey Durbin </li></ul></ul></ul></ul><ul><ul><ul><ul><li>DRE’s and subjects </li></ul></ul></ul></ul><ul><ul><ul><li>WSLH </li></ul></ul></ul><ul><ul><ul><ul><li>Amy Miles </li></ul></ul></ul></ul>www.NMSLabs.com 1.866.522.2216

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