STOP DRUGGED DRIVING

Bruce A. Goldberger, Ph.D., DABFT

Professor and Director of ToxicologyCollege of Medicine - Pathology & Psychiatry

President, American Academy of Forensic Sciences

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.

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

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

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

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)

The Grand Rapids Study

Relative Probability of Causing an Accident

www-nrd.nhtsa.dot.gov/pdf/nrd-30/NCSA/TSF2005/AlcoholTSF05.pdf

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Traffic Fatalities

Total FatalitiesNo AlcoholLow AlcoholHigh AlcoholVery High Alcohol

Traffic Fatalities in Florida

Drugged Driving In a Campus Community

Excessive drinking threatens the academic mission of colleges, and the health and

safety of their communities.

Research Team

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

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)

Establishment Visits

Each establishment visit consisted of:(1) Observational

assessment inside establishment

(2) Sidewalk interviews outside establishment

Sidewalk Interviews

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

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

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.

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)

Oral Fluid Specimen

Participants provided a saliva sample to be examined for genetic markers linked to excessive drinking and alcohol dependence.

Oral Fluid Specimen

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

Breath Sample

Participants provided a breath sample to estimate blood alcohol concentration.

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

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

Effects of Drugs on Driving

• CoordinationEffects on nerves/muscles - steering, braking, accelerating, manipulation of vehicle

• Reaction TimeInsufficient response - reaction

• JudgmentCognitive effects, risk reduction, avoidance of potential hazards, anticipation, risk-taking behavior, inattention, decreased fear, exhilaration, loss of control

• TrackingStaying in lane, maintaining distance

• AttentionDivided, not focussed. Time-shared task with high demand for info processing

• Perception90% of info processed while driving is visual. Glare resistance, recovery, dark and light adaptation, dynamic visual acuity

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

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)

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.)

Determining “Under the Influence”

A. Driving pattern

B. Impairment Visual Physiological Performance

C. Positive toxicology Ethanol Drugs

- blood vs. urine

- parent vs. metabolite

- quantitation

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

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

Toxicology IssuesQuantitative 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?

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

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

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”

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

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

Quantitation

Numbers help, but certainly aren’t the end all answer

Therapeutic vs. abuse vs. toxic Research is still evolving

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

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”?

Poly-drug Challenges

Inconsistent symptoms Determine dominant drug Show consistencies with that drug Explain how other drugs present

may contribute to effects

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

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)

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

Analytical Recommendations

Survey Data

Ten Drugs Most Often Identified

Recommended Scope of Cutoffs

Medical/Clinical/Forensic Diagnostics

BREATH

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

Target Molecules in Breath

O

HO

OH

OH

OHHO

-D-glucose

OH

H3C CH3

CH3CH3

Propofol

H3C

O

N

N

Fentanyl

Ethanol

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

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 =

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)

Breath Propofol - Measurements

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TOT. SIG.

PROPOFOL RELATIVE BREATH CONCENTRATION PROFILE

TIME (MIN.)

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(C

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120 μg/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

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TOT. SIG.

PROPOFOL RELATIVE BREATH CONCENTRATION PROFILE

TIME (MIN.)

TO

TA

L S

IGN

AL

(C

OU

NT

S)

120 μg/Kg/min

50 μg/Kg/min

200 mg bolus

40mg bolus, 100 μg/Kg/min

40 mg bolus

60 mg bolus

infusion off

Will we develop per se laws for drugs and driving?

And will you really be driving under the influence?

In the future…

Recent Trends in Florida

Marijuana Xanax Methamphetamine Inhalants - Difluoroethane

(Dust-off)

Thank You!