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  • There are at least two subtypes of the cannabinoid receptor - CB1 and CB2 receptors. The CB1 receptors are highly expressed throughout the peripheral and central nervous systems. Specifically, the CB1 receptors are highly expressed in the hippocampus, cortex, basal ganglia, cerebellum and spinal cord. This distribution accounts for the effects of cannabinoids on memory, cognition and movement. Both CB1 and CB2 cannabinoid receptors are coupled to inhibitory G-proteins. Activation of the cannabinoid receptors causes inhibition of adenylate cyclase and a subsequent decrease in the concentration of cAMP in the cell, resulting in the inhibition of neurotransmission. CB2 receptors are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells
  • So called herbal or legal highs became popular in Europe in late 2008. Analysis of the materials in a laboratories in Germany, found the presence of 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. These went by the names Spice, Spice Gold, Smoke, Sence, Space, Other materials were found to
  • This series of compounds were first synthesized by Walter Huffman and his group at Clemson in 1998 and were shown to have potent Cannabinoid receptor binding. They have recently been identified as being the common components of a series of “incense blends” being sold as K2, and related products, K2 Blonde, K2 Summit, etc.
  • Receptor distribution in brain correlates with areas involved in physiological, psychomotor and cognitive effects
  • On cell membranes CB1 – primarily central and Cardiovascular CB2 – primarily peripheral – immune system

Salvia K2 Dre Conference 2010 Presentation Transcript

  • 1. Barry K Logan PhD, DABFT Director of Forensic Services IACP DRE Conference 2010 Pittsburgh PA New Highs: Salvia and K2: Solutions for the DRE Program From the Premium Provider of Forensic Services
  • 2. NMS Labs DRE Offering
    • Fast TAT 3-5 days
    • Proactive Customer Support
    • New Forensic Report Format
    • Differentiating Reference Comments
      • Specific to Drug Impaired Driving
    • Fast Access to Results Reports Online
    • Wiki Access to Relevant Technical Topics
    • Quality Backed by ABFT accreditation
    For informational purposes. NMS Labs, When you need to know, the associated logo and all associated NMS Labs marks are the trademarks of NMS Labs. © Copyright 2009 NMS Labs. All Rights Reserved. 08/09
  • 3. NMS Labs DRE Test Offering
    • Blood/Urine
    • Scope: Cannabinoids, Cocaine metabolite, Amphetamines, MDMA, PCP, Barbiturates, Benzodiazepines, Opiates, Methadone, Oxycodone, Propoxyphene.
    • Confirmations included in price.
    • Proactive contact on negative cases.
    For informational purposes. NMS Labs, When you need to know, the associated logo and all associated NMS Labs marks are the trademarks of NMS Labs. © Copyright 2009 NMS Labs. All Rights Reserved. 08/09
  • 4. Marijuana Most popular recreational drug after alcohol and tobacco. #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.
  • 5. Synthetic Cannabinoids Synthetic drugs that mimic the effects of cannabis. Investigational use for appetite, blood pressure, nausea, etc First synthesized in the 1970’s Sprayed onto dried plant leaves, flowers and stems, and smoked. Legal or unregulated in most US states.
  • 6. Marijuana to Spice THC HU-210 CP 47,497 Cannabicyclohexanol
  • 7. Clemson Series - JWH JWH-018 JWH-073 JWH-250
  • 8. 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
  • 9. Herbals - Botanical Substrate Glycyrrhiza glabra (Cultivated Liquorice) Astragalus membranaceus (Milk Vetch) Verbascum thapsus (Common Mullein) (Uchiyama et al, 2010)
  • 10. Synthetic Cannabinoids
  • 11. Synthetic Cannabinoids – Drug ID
      • Agilent 5973 Mass Spectrometer
      • Agilent 6890 Gas Chromatograph
      • Electron Impact mode
      • Full scan
      • Total run time 10 minutes
      • Sensitivity 20-50 ug/g
  • 12. 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)
  • 13. 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 -
  • 14. Missouri K2 Administration Study
    • IRB Human subjects approval obtained from University of Central Missouri.
    • Six subjects smoked K2 Summit, Citron, Standard
    • Each contained JWH-018 and JWH-073, or CP47,497
    • Subjects performed SFST’s, cognitive tests and DRE Exam.
    • Blood, urine and oral fluid collected.
  • 15. Missouri K2 Administration Study
    • Onset of effects in about 2-3 minutes
      • Dry mouth
      • Light headedness
      • Blurred vision
      • Agitation, Motor restlessness
      • Time dilation
    • DRE Exam
      • Increased pulse and blood pressure
      • Lack of convergence
      • No HGN, or VGN
      • Pupils normal, muscle tone normal
    • SFST’s
      • 3-4 inches of sway, leg body tremors
      • Loss of balance
      • Loss of motor coordination
  • 16. York County PA, DRE Case
      • Vehicle crashed into snowbank
      • Subject appeared drunk or high, difficulty speaking, incoherent, mumbling, slow slurred speech, nonsense, giggling.
      • Had smoked “Space” less than 2 hours before.
      • “ I’m not a DUI. The stuff I smoked is legal. You can’t arrest me”
      • Courtesy Cpl Brian Torkar, PSP
  • 17. York County PA, DRE Case
      • Pulse 96-88, BP 150/80
      • Eyes watery, red, bloodshot, pupils dilated
      • Eyelids droopy, HGN present, no VGN
      • Lack of convergence
      • SFST’s
        • 4 inches of sway on Romberg
        • Lost balance, used arms on WAT
        • Swayed, used arms on OLS
        • Poor finger to nose performance
      • Courtesy Cpl Brian Torkar, PSP
  • 18. Synthetic Cannabinoids - Biologicals
      • Agilent 6230 TOF Mass Spectrometer
      • Agilent 1200 binary UPLC
      • ESI source with Nitrogen Jet
      • High resolution mode.
      • Total run time 10 minutes
      • Sensitivity 0.1ng/mL
      • Confirmed by LCMS/MS
    Analyte Accurate Mass JWH-018 341.45272 JWH-073 327.42584 JWH-250 335.44600
  • 19. Target analytes 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
  • 20. York County PA, DRE Case
      • Drug Identification
        • “ Space” contained JWH-018, traces of JWH-200
      • Toxicology
        • Blood collected approximately 4 hours after use.
        • Positive for diphenydramine <50ng/mL
        • Positive for JWH-018 by directed analysis, LC-TOF
  • 21. 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
  • 22.
    • Salvia; Sal; Magic Mint, Mystic Sage
    • Ska Pastora; Sally-D; Diviners Sage; Shepherdess's Herb; ska Maria Pastora; hojas de Maria; yerba de Maria;
    • “ Salvia divinorum is a sprawling perennial herb found in the Sierra Mazatec region of Mexico. Its leaves contain the extremely potent Salvinorin A. It has a history of buccal use as a divinatory psychedelic, and has been widely available since the mid 1990s primarily as a smoked herb. Its effects are considered unpleasant by many people.”
    http://www.erowid.org/plants/salvia/salvia.shtml Salvia Divinorum
  • 23. Salvia Divinorum - Chemistry
    • Active component – Salvinorin A
    • Other natural products –
      • Salvinorin C-G, Divinatorins A-E, Salvinicin A-B
    • Synthetic derivatives are under investigation for treatment of Alzheimers, Parkinsons, schizophrenia, and stimulant dependence.
    Vortherms and Roth, 2006; Grundmann et al, 2007
  • 24. Salvia Divinorum - Use
    • Currently sold in head shops, tobacco shops, and online.
    • SAMHSA estimates 750K – 1M last year use (2007).
    • “ Buy Salvia” Google search generates 285,000 hits.
    • Available as plants, crushed leaves, extract
    • Extracts contain Salvinorin A and B
    Tsujikawa et al, 2008 (mg/g) Sal A Sal B Leaves 3.2 - 5.0 0.10 – 0.17 Extract 4.1 – 38.9 0.26 – 2.42
  • 25. Salvia Divinorum - Effects
    • Following smoking, effects are intense but short lived.
    • Psychedelic–like changes in visual perception.
    • Mood and somatic changes
    • Modified perception of external reality.
    • Decreased ability to interact with self or surroundings
    Gonzalez, et al, 2006
  • 26. Salvia– Adverse Effects Vohra et al, 2009
    • 18 Isolated Salvia Exposures
    Clinical Feature Frequency Altered Mental state 7 Hallucinations 3 Excessive laughter 1 Dizziness 1 Mydriasis 2 Flushing 3 Diaphoresis 1 Tachycardia 2 Palpitations 1 Hypoglycemia 1
  • 27. Salvia Divinorum - Effects Gonzalez, et al, 2006 Best Things Worst Things Unpleasant After-Effects The “Trip” 13 Duration 12 Tiredness 4 Happiness 9 Control 5 Heaviness 4 Dissociation 6 After-effects 4 Dizziness 3 Visual Effects 5 Physical fx 3 Exhaustion 3 Rapid onset 3 Intensity 2 Grogginess 1 Great potency 3 Mental slowness 1 Relaxation 2
  • 28. Salvia Divinorum - Pharmacodynamics
    • C 11 Salvinorin A administered to baboons (IV).
    • Extremely rapid uptake
    • Peak activity achieved in 40 seconds
    • Represents 3.3% of dose
    • PET kinetics match onset and dissipation in humans
    Hooker et al, 2008
  • 29. Salvia Divinorum - Metabolism Tsujikawa et al, 2009
  • 30. NMS Labs - Salvinorin Analysis
      • Positive ion electrospray liquid chromatography tandem mass spectrometry (LC-MS/MS).
      • Blood, urine, plasma
      • Single step L/L extraction
    Test requirements available at w ww.nmslabs.com Analyte MRM MRM RT (min) Sal A 433/373 433/295 6.67 Sal A-d3 436/376 N/A 6.67 Sal B 389/313 389/295 5.88
  • 31. NMS Labs – Salvinorin B Analysis
    • Sal B
    • LOQ
      • 1ng/mL
    • LOD
      • ~0.25ng/mL
  • 32. Salvia Divinorum –Human Study
    • Two subjects with prior experience with hallucinogens, smoked 75mg of salvia leaves, for three minutes, ad lib.
    • Oral fluid collected at 1 hour post smoking.
    • Urine collected at 0-1.5 hrs, and 1.5-9 hrs.
    • Sweat patches applied and removed 2 hrs after smoking.
    • “ Unfortunately… blood collection was not possible… both volunteers experienced intense hallucinations that started about 30 seconds after inhaling peaking at 3-5 minutes, and lasting about 15-20 minutes. During that period blood drawing was considered unsafe, and at the end of the experience the subjects refused blood drawing.”
    Picini et al, 2005
  • 33. Salvia Divinorum –Human Study
    • Dose 0.58mg Salvinorin A administered.
    • Only Salvinorin A measured
    Picini et al, 2005 Oral fluid (ng/mL) Urine (ng/mL) Sweat Patch 1 hr 0-1.5hrs 1.5-9.5hrs 2 hrs Sub 1 25.0 10.9 N.D. N.D. Sub 2 11.1 2.4 N.D. N.D.
  • 34. Salvinorin A and B – Stability * unpreserved Days 1 2 9 14 28 Blood NaF 25 o C N/ Y N/ Y N/ Y N N Blood NaF 4 o C N/ Y N/ Y N/ Y N N Blood NaF -20 o C Y Y Y Y Y Plasma NaF 25 o C Y Y Y Y N Plasma NaF 4 o C Y Y Y Y Y Plasma NaF -20 o C Y Y Y Y Y Urine* 25 o C Y Y N/ Y N N Urine* 4 o C Y Y Y Y Y Urine* -20 o C Y Y Y Y Y
  • 35. Acknowledgements
      • Analysis
        • NMS Labs
          • Allan Xu
          • Matt McMullin
          • Lindsay Reinhold
      • Penn. State Police
        • Cpl Brian Torkar
      • Agilent
    • Join Forensic Toxicology on www.LinkedIn.com
      • Dosing Study
        • UCMO
          • Bob Welsh
          • Tracey Durbin
          • DRE’s and subjects
        • WSLH
          • Amy Miles
  • 36. NMS Labs Salvia and K2 test codes
      • Toxicology
      • 8070B/S/P/U - Drug Impaired Driving/DRE Toxicology Panel
      • 4150B/S/P/U - Salvinorin A & B
      • 7744B/S/P - Special Request for Synthetic Cannabinoids
      • Drug Identification
      • 7201LI/SL - Controlled Substances/Pharmaceuticals
      • 7472SL - Synthetic Cannabinoids – solid
      • 7461LI/SL - Salvinorin A identification – liquid/solid