1. S TOP D RUGGED D RIVING Bruce A. Goldberger, Ph.D., DABFT Professor and Director of Toxicology College of Medicine - Pathology & Psychiatry President, American Academy of Forensic Sciences

2. Alcohol / Drugs and Driving Which Drugs Can Affect Driving?  Any drug that affects the brain’s perception, collection, processing, storage or critical evaluation processes.  Any drug that affects communication of the brain’s commands to muscles or organ systems.  For the most part, drugs that affect the central nervous system.

3. Alcohol and Drugs Drug Impaired Driving Results in Injuries and Deaths –  No database to track injuries and deaths  Problem is under-reported, under- recognized  Drugs are a constant factor in traffic crashes  Societal impact unknown

4. Alcohol and Drugs National Center for Injury Prevention and Control –  “During 2005, 16,885 people in the U.S. died in alcohol-related motor vehicle crashes, representing 39% of all traffic-related deaths (NHTSA 2006).”  “In 2005, nearly 1.4 million drivers were arrested for driving under the influence of alcohol or narcotics (Department of Justice 2005).”  “Drugs other than alcohol (e.g., marijuana and cocaine) are involved in about 18% of motor vehicle driver deaths. These other drugs are generally used in combination with alcohol (Jones et al. 2003).” www.cdc.gov/ncipc/factsheets/drving.htm

5. Drug Impaired Driving  Drugs detected in 10 to 22% of drivers involved in crashes, often in combination with alcohol  Drugs detected in up to 40% of injured drivers requiring medical treatment  Drug use among drivers arrested for motor vehicle offenses is 15-50%  Highest rates reported among those arrested for impaired or reckless driving Source: NHTSA, National Highway and Traffic Safety Administration

6. Young People  Incidence of non-alcohol related driving impairment higher among young people  22% of young people report using drugs prior to driving  23.5% of drivers under 21 tested positive for drugs (DHHS)  16-20 year olds more than twice as likely to drive after non-alcohol drug use compared with those over 21y (SAMHSA)  20% of twelfth grade students report smoking marijuana in cars (PRIDE)

8. The Grand Rapids Study Relative Probability of Causing an Accident

9. www-nrd.nhtsa.dot.gov/pdf/nrd-30/NCSA/TSF2005/AlcoholTSF05.pdf Traffic Fatalities in Florida

10. Drugged Driving In a Campus Community Excessive drinking threatens the academic mission of colleges, and the health and safety of their communities.

11. Research Team

12. Binge Drinking  Heavy episodic or “binge” drinking has been associated with numerous problems in the college student population:  sexual assault  violent behavior  physical injury  property damage  high-risk sexual behavior  poor academic performance  death

13. Methods  This study was conducted during six nights of December, 2006 and May, 2007.  Sidewalk interviews and breath alcohol tests were conducted with 291 patrons exiting 15 drinking establishments in Gainesville, FL.  University of Florida (49,000 students)  Santa Fe Community College (16,000 students)

14. Establishment Visits Each establishment visit consisted of: (1) Observational assessment inside establishment (2) Sidewalk interviews outside establishment

15. Sidewalk Interviews Each sidewalk interview consisted of a 3-5 minute interview and breath alcohol test.

16. Sidewalk Interviews  Examples of questions asked during interview:  When did you start drinking today?  How many drinks have you had today?  Did you take advantage of a drink special today?  After the interview and breath test, participants were given a “walk-away” card:  phone numbers for safe ride services  local sources of help for an alcohol problem  contact information of principal investigator and institutional review board

17. Sample  Of approximately 600 exiting patrons, 291 agreed to participate.  61% were men  86% were college students  84% were 21 years of age or older  Average BrAC =0.091 (range 0.0-0.281)  58% above the legal limit to drive (BAC ≥.08)  No sex differences in regards to BAC.

18. The Interview  After being recruited and giving verbal informed consent, participants completed a 10-15 minute interview and anonymous survey about their behaviors that night.  Participants also provided 3 specimens – breath and oral fluid (2x)

19. Oral Fluid Specimen  Participants provided a saliva sample to be examined for genetic markers linked to excessive drinking and alcohol dependence.

20. Oral Fluid Specimen  Participants provided an oral fluid sample to detect recent use (i.e., tobacco, marijuana, other illicit and prescription drugs).

21. Breath Sample  Participants provided a breath sample to estimate blood alcohol concentration.

22. Sample  Demographics (N=477)  65% were men  77% were white  91% were college students  76% were 21 years of age or older  Average BAC =0.091 (range: 0 - 0.262)  58% above the 0.08  25% were under 21 years of age  21% planned to drive home in less than an hour  15% used drugs besides alcohol to get high that night

23. Results of Drug Testing Of those participants who provided an oral fluid sample to detect recent drug use,  95% reported drinking alcohol that night  12% reported using drugs other than alcohol 11% tested positive for drugs 8% tested positive for marijuana 2% tested positive for cocaine 2% tested positive for multiple drugs

25. Effects of Drugs on Driving Coordination Effects on nerves/muscles - steering, braking, accelerating, manipulation of vehicle Reaction Time Insufficient response - reaction Judgment Cognitive effects, risk reduction, avoidance of potential hazards, anticipation, risk-taking behavior, inattention, decreased fear, exhilaration, loss of control Tracking Staying in lane, maintaining distance Attention Divided, not focussed. Time-shared task with high demand for info processing Perception 90% of info processed while driving is visual. Glare resistance, recovery, dark and light adaptation, dynamic visual acuity

26. Alcohol and Drugs Drugs commonly associated with impaired driving –  Cannabinoids (marijuana)  Depressants: sedative/hypnotics, muscle relaxants, antihistamines  Stimulants: cocaine, methamphetamine  Narcotic analgesics: morphine, codeine, hydrocodone, hydromorphone, oxycodone, methadone

27. Alcohol and Drugs Depressants commonly associated with impaired driving –  Sedative/hypnotics including diazepam and alprazolam (Valium and Xanax)  Muscle relaxants including carisoprodol (Soma)  Antihistamines including diphenhydramine (Benadryl)

29. Basis for the Opinion of Impairment?  Impairment is based on knowledge of the drug(s), intended effects, side effects and toxic effects  The toxicologist can rarely give an opinion based upon the toxicology report alone  The opinion may depend on the context of the case and information gathered by the investigator (situation, environment, observations, driving pattern etc.)

30. Determining “Under the Influence” A. Driving pattern B. Impairment  Visual  Physiological  Performance C. Positive toxicology  Ethanol  Drugs - blood vs. urine - parent vs. metabolite - quantitation

31. What the Toxicologist cannot do….  Determine impairment in a specific individual from a blood concentration alone  Determine exactly how much drug was taken  Determine exactly when a drug was taken

32. Drug Interpretation Issues  Multiple drug use  Tolerance  History of drug use (chronic vs. naïve)  Health  Metabolism  Genetic/ethnic differences  Individual sensitivity/response  Withdrawal  Put in context of case e.g. environmental factors

33. Toxicology Issues Quantitative or Qualitative Analysis?  Therapeutic, toxic, lethal concentration in blood?  High or low dose?  Recent use or residual drug?  Effect of tolerance, history of drug use  Individual sensitivity/response  Effect of other drugs?

34. Drugs in Urine  Good specimen to screen for large number of drugs and drug classes  Typically see metabolites  Usually indicates drug use within the past 2-3 days or more  Cannot definitively establish impairment  “Consistent with” or “Explanation for” the impairment

35. Drugs in Blood  If drug is present in the blood, it is assumed to be affecting central nervous system and other target organs  Typically see parent compounds (or both)  Quantitation is vital to prosecution

36. Urine vs Blood  Since urine is an end-product of absorption, distribution and metabolism, a drug in the urine does not show it is still circulating in the body and producing an effect  Cannot say one is “under the influence”

37. Urine vs Blood  Blood however is circulating throughout the body and one is experiencing the drug’s effects – “under the influence”  But, is one “impaired”?  Must know pharmacology  Drugs and Driving literature evolving

38. Parent vs Drug Metabolite  Parent drug is the compound ingested  Metabolites are formed by enzymatic or chemical processes in the body  Metabolites can be pharmacologically active or inactive, more or less toxic than the parent  Metabolites usually have longer half-lives so will be detected longer and exert its effects longer than the parent drug and may help determine time frame of use

39. Quantitation  Numbers help, but certainly aren’t the end all answer  Therapeutic vs. abuse vs. toxic  Research is still evolving

40. Drug Impairment Issues  More complex than alcohol  Often in combination with other drugs and/or alcohol (additive or synergistic effects)  Scientific literature is complex  May require a toxicologist to interpret the results and provide an opinion  These complex issues must be explained to the court using every day language

41. It Gets Very Complicated…  Unusual or incomplete signs  Individual responses vary  Phase of the drug use (up or down?)  Chronic or naïve drug user  Tolerance  Are there “normal ranges” ?

42. Poly-drug Challenges  Inconsistent symptoms  Determine dominant drug  Show consistencies with that drug  Explain how other drugs present may contribute to effects

43. How it’s done now  Work with the triad of driving pattern, impairment and positive toxicology whenever possible  Research the drugs and driving literature before forming an opinion  Is the number meaningful?  Missing information needs to be carefully considered  Be prepared to discuss general issues in cases where impairment cannot be definitively determined

44. Approaches to Prosecution  May require the driver to be “affected by”  May require the drug to impair a driver’s ability to operate a vehicle safely, incapable of driving safely or require a driver to be under the influence, impaired or affected by an intoxicating drug  Per-se or zero tolerance drug laws  Make it a criminal offense to have a specified drug or metabolite in the body while operating a motor vehicle  Any amount (zero tolerance) or a specified level (per se)

45. How is the testing done…  Specimens - blood, urine and oral fluid  Immunoassay screen for drug or drug panel Homogeneous immunoassay ELISA  Gas Chromatography Screen GC or GC-MS  Confirmation/Quantitation by mass spectrometry GC-MS or GC-MS-MS LC-MS or LC-MS-MS

46. Analytical Recommendations

47. Survey Data

48. Ten Drugs Most Often Identified

49. Recommended Scope of Cutoffs

50. Medical/Clinical/Forensic Diagnostics BREATH

51. Specific Molecular Entities in Breath Endogenous Biomarkers of Disease Glutamate – Brain injury (trauma or stroke) Stress markers – Inflammatory mediators Histamine – Asthma Exogenous Drugs – particularly those with a narrow TI Chemotherapeutic agents Antimicrobials THC, cocaine, GHB, ecstasy, etc. – Drugs of Abuse Biomarker Drugs – Assess enzyme competence

52. Target Molecules in Breath O HO OH OH OHHO  -D-glucose Propofol Fentanyl Ethanol

53. Human Lung and Breath Ideal Media for Diagnostics (Breath = Gas + Liquid)  Blood  Lungs  Breath  Blood transports all chemicals  Breath - volatiles and non-volatiles 100% Cardiac Output  Lungs  Excellent transport given lungs surface area for diffusion Breath  free drug blood concentration Rapid kinetics Non-invasive Not “dirty” versus other sampling sites Unprecedented opportunities for portable, accurate, sensitive/specific, non-invasive, real time (breath-to-breath) POC diagnostics for many medical applications

54. Why do we need nano for breath detectors? NANO Answer: Nano provides the “horsepower” to sensitively and specifically detect low concentrations of analytes. 2 critical factors in breath: 1) physiologically relevant free drug concentrations, and 2) relationship between blood and breath drug concentrations. Potent Drugs ± Type D Behavior =

55. 3 general types: Antibodies – proteins (amino acids)  Many commercially available; vast array available including those directed against multiple epitopes on a specific molecule  Functional well in vivo and ex vivo  Excellent for nano-based breath diagnostics Aptamers – DNA/RNA (oligonucleotides)  Few available for small molecules; most proteins  Functional poorly in vivo; better ex vivo Enzymes – catalyze degradation of substrates  Can have extraordinary selectivity for specific substrates  e.g., glucose oxidase for glucose Molecular Recognition Entities (MREs)

56. Breath Propofol - Measurements 4035302520151050 - 1000 0 1000 2000 3000 4000 5000 6000 TOT. SIG. PROPOFOL RELATIVE BREATH CONCENTRATION PROFILE TIME (MIN.) TOTAL SIGNAL (COUNTS) 120μg/Kg/min 50 μg/Kg/min 200 mg bolus 40mg bolus, 100 μg/Kg/min 40 mg bolus 60 mg bolus infusion off 4035302520151050 - 1000 0 1000 2000 3000 4000 5000 6000 TOT. SIG. PROPOFOL RELATIVE BREATH CONCENTRATION PROFILE TIME (MIN.) TOTAL SIGNAL (COUNTS) 120μg/Kg/min 50 μg/Kg/min 200 mg bolus 40mg bolus, 100 μg/Kg/min 40 mg bolus 60 mg bolus infusion off

57. Will we develop per se laws for drugs and driving? And will you really be driving under the influence? In the future…

58. Recent Trends in Florida  Marijuana  Xanax  Methamphetamine  Inhalants - Difluoroethane (Dust-off)

59. Thank You!