Drugs and workplace safety

Professor Edward Ogden PSM MA MBBS BMedSc DipCrim GradCertMgt FRACGP FAChAM FFCFM(RCPA)

What is ICADTS?

• ICADTS is an independent nonprofit body whose only goal is to reduce the mortality and morbidity brought about by misuse of alcohol and drugs by operators of vehicles in all modes of transportation.

• The Council sponsors international and regional conferences.

International Council on Alcohol, Drugs and Traffic Safety

Illegal Drugs and Driving Alcohol Ignition Interlocks Alcohol Biomarkers Prescribing Guidelines for Medicinal Drugs and Driving Clinical Signs of Impairment for Drugs Other than Alcohol Young Drivers Standardization of Reporting Alcohol and Drug Involvement in Fatal Crashes Low and Middle Income Countries Designer Drugs and Driving Young Scientists

Upcoming International Conference www.t2019.org

www.icadtsinternational.com

T2022

Rotterdam, The Netherlands

Worry about what?

Drugs and work

The problem with cannabis!

What to do about ICE

Medication and driving

1

2

5

3

4

Is alcohol a useful model? Where is the good data?

How big is the drug problem in Australia?

CIOBANU, L., FERRARI, A., E ERSKINE, H., SANTOMAURO, D., CHARLSON, F., LEUNG, J., AMARE, A., OLAGUNJU, A., WHITEFORD, H. & BAUNE, B. 2018. The prevalence and burden of mental and substance use disorders in Australia: Findings from the Global Burden of Disease Study 2015.

= 1.2 million Australians

WHICH DRUG SHOULD WE WORRY ABOUT?

Is alcohol a useful model?

• Ethanol is a simple molecule

• Taken in gram quantities

• Zero-order pharmacokinetics

• Risks studied for 150 years

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0 0.05 0.1 0.15 0.2

BAC

Re

lati

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isk

. . .

How much matters?

If you can measure the alcohol there is an effect

How many drinks for your pilot ?

0

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30

40

50

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80

Time

Del

ta-9

-TH

C in

ng/

ml

Placebo 0 0 0 0 0 0 0

1.74% THC 0 55.46 12.84 6.16 4.32 3.18 2.53

2.93% THC 0 70.59 13.85 6.79 5.13 3.72 2.42

Before

Smoking

THC

0 mins

after

smoking

20 mins 50 mins 75 mins 100 mins 125 mins

Other drugs are not so simple

• Complex pharmacodynamics (e.g. cannabis)

• Long half life (e.g. methamphetamine)

• Complex relationship between dose and risk o Exponential - sedatives like alcohol, benzodiazepines o Quadratic - cannabis, opiates, antidepressants

• Drug interactions

o Symbiotic o Antagonistic o Complex

0 0.05 0.1 0.15 0.2

0

50

0

Re

lati

ve R

isk

. . .

Alcohol

Cannabis Peak subjective effects

Peak impairment

So where do we look for good data?

• Epidemiology

• National Household Drug Survey

• Police data • Random Drug Testing

• Drug screening post collision

• DUI (drive under the influence)

• Responsibility studies

• Case matched studies

Prevalence

Risk

Knoche, A. DRUID: Overview of the Project Results. in International Conference on Alcohol, Drugs and Traffic Safety (T2013), 20th, 2013, Brisbane, Queensland, Australia. 2013.

Responsibility analysis

The involvement of drugs in drivers of motor vehicles killed in Australian road traffic crashes Olaf H. Drummer, Jim Gerostamoulos , Helen Batziris, Mark Chua, John Caplehorn, Michael D. Robertson, , Philip Swann, Accident Analysis and Prevention 36 (2004) 239–248

0

2

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12

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20

Control Drug/spresent

0.05% to0.10%*Alcohol

0.10% to0.15%*Alcohol

THCpresent

THC>5ng/ml

Alcohol &THC

Stimulants

Landmark study of fatality risk

0

10

20

30

40

50

60

70

Control Drugs present BAC. 0.05% to0.10%

BAC. 0.10% to0.15%

THC present THC >5ng/ml Alcohol & THC Stimulants Benzodiazepines Opiates

Od

ds R

ati

o

Ogden et al. (n=1809) Drummer et al. (n=3398) Gadegbeku et al. (n =10,308)

Drummer, O.H., et al., The involvement of drugs in drivers of motor vehicles killed in Australian road traffic crashes. Accident Analysis And Prevention, 2004. 36(2): p. 239-48. Ogden, E., et al., The relationship between accident culpability and presence of drugs in blood from injured Victorian drivers., in 19th International Council on Alcohol Drugs and Traffic Safety. 2010: Oslo. Gadegbeku, B., E. Amoros, and B. Laumon, Responsibility study: main illicit psychoactive substances among car drivers involved in fatal road crashes. Annals Of Advances In Automotive Medicine 2011. 55: p. 293-300.

The odds of responsibility for fatal and non-fatal collisions are different

Meta-analysis of risk

0

1

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7

8

9

Control Amphetamine Analgesics Antidepressants Antihistamines Benzodiazepines THC present Opiates Zopiclone

Od

ds R

ati

o

Fatal Injury Property damage

Elvik, R., Risk of road accident associated with the use of drugs: a systematic review and meta-analysis of evidence from epidemiological studies. Accid Anal Prev, 2013. 60: p. 254-67.

Combining psychotropic drugs

Not reponsible

Contributory

Responsible

DRUG & ALCOHOL FREE

30%

[CATEGORY

NAME]

Contributory Responsi

ble

USING 1 DRUG

70%

Not responsibel Contributor

y

Responsible

USING 2 DRUGS

80%

Not reponsible Contributor

y

Responsible

3 DRUGS

90%

Responsible

4 OR MORE DRUGS

100%

Odds Ratios for Drug Classes

• THC (Cannabis) 1.05 • Antidepressants 0.87 • Narcotic Analgesics 1.14 • Sedatives 1.27 • Stimulants 0.94 • Illegal Drugs 1.04 • Legal Drugs 1.03

(Adjusted for Demographic Variables: Age, Gender And Race/Ethnicity)

Compton, R. P. & Berning, A. (2015, February). Drug and alcohol crash risk. (Traffic Safety Facts Research Note, Report No. DOT HS 812 117). Washington, DC: National Highway Traffic Safety Administration.

Alcohol 0.05% 2.07 0.08% 3.93 0.10% 5.64 0.15% 12.18 0.18% 18.17 0.20%+ 23.29

Cannabis

Berghaus, G., et al., Meta-analysis of empirical studies concerning the effects of medicines and illegal drugs including pharmacokinetics on safe driving. 2011, University of Würzburg.

0 1 2 Time in hours

Subjective high, time course and impairment not related

Rapid Change in Legal Status of Marijuana Raises Important Issues

• Changes in use patterns

• More prevalence in traffic

• More prevalence in crash-involved drivers

• But does it pose greater risk?

U.S. Example: Washington State

Following legalisation the proportion of drivers

in fatal crashes with detectable THC doubled

8.3% in 2013

17.0% in 2014.

Does not necessarily indicate impairment or

that THC was causal in the crash.

Tefft, et al. Prevalence of Marijuana Involvement in Fatal Crashes: Washington, 2010 – 2014. AAA Foundation for Traffic Safety (May 2016)

Acute impairment due to THC

• Consistent evidence of impairment in many domains of cognition – Psychomotor speed

– Attention

– Visual processing

– Perception

– Executive function?

– Verbal fluency ok; working memory impaired

Naïve or less regular users less impaired

Abstinence in heavier users causes larger impairments

CREAN, R. D., CRANE, N. A. & MASON, B. J. 2011. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. Journal of addiction medicine, 5, 1.

Head Movements & Jerks

Acute effects on coordination

How well can per se laws work?

• THC concentration alone

• misclassified a substantial number of drivers as impaired

• misclassified a substantial number of drivers as unimpaired

• Simple THC levels cannot be scientifically supported

• THC impairment matters!

Interpreting THC • Formulae published 1992 and validated 2005, 2006

𝑡𝑖𝑚𝑒 = 10(−0.698∗log[𝑇𝐻𝐶]+0.687)

𝑡𝑖𝑚𝑒 = 10(0.576∗log([𝑇𝐻𝐶𝐶𝑂𝑂𝐻]/[𝑇𝐻𝐶])−0.176)

Huestis, M. A., J. E. Henningfield, et al. (1992). "Blood cannabinoids. II. Models for the prediction of time of marijuana exposure from plasma concentrations of delta

9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH)." J Anal Toxicol 16(5): 283-90.Huestis, M. A., A. Barnes, et al.

(2005). "Estimating the time of last cannabis use from plasma delta9-tetrahydrocannabinol and 11-nor-9-carboxy-delta9-tetrahydrocannabinol concentrations." Clin

Chem 51(12): 2289-95.Huestis, M.A., et al., Estimating time of last oral ingestion of cannabis from plasma THC and THCCOOH concentrations. Ther Drug Monit,

2006. 28(4): p. 540-4.

Prediction based on THC alone THC Levels after Smoking

0.0%

88.0%

97.7%

88.2%

78.6%

68.2%

0

10

20

30

40

50

60

70

80

Before 0 min 20 min 50 min 75 min 100 min 125 min

time

ng

/ml

Low dose High Dose Accuracy of prediciton

Smoking

Huestis, M. A., et al. (2005). "Estimating the time of last cannabis use from plasma delta9-tetrahydrocannabinol and 11-nor-9-carboxy-delta9-tetrahydrocannabinol concentrations." Clinical Chemistry 51(12): 2289-2295. Huestis, M. A., et al. (2006). "Estimating time of last oral ingestion of cannabis from plasma THC and THCCOOH concentrations." Therapeutic Drug Monitoring 28(4): 540-544. Ogden, E., et al. (2007). Validation of a model for estimating time of last cannabis use from known concentrations of tetrahydrocannabinol and the major metabolite. ICADTS, Seattle.

Case Study • 7.15 am offending driver crossed to incorrect side of highway

– Had driven 42 km

• Killed drivers of two cars and injured passengers

• Denied drug use

• Blood sample at 9.00 am – THC 10 ng/ml

– TCH-COOH 40 ng/ml

• Mathematical model predicts smoking within 4 hours of blood test – immediately before or whilst driving

Medicinal Marijuana: The cart before the horse

Professor Edward Ogden PSM MA MBBS BMedSc DipCrim GradCertMgt FRACGP

FAChAM FFCFM(RCPA)

The cart IS before the horse Human studies tells us …

• There is good evidence for use in

• chronic pain, multiple sclerosis, nausea

• There is limited evidence for use in

• improving weight loss in HIV, tics in Tourette Syndrome, PTSD

• Decrease in inflammatory markers

• There is evidence that it is ineffective in

• Dementia, cancers, glioma

D'SOUZA, D. C. & RANGANATHAN, M. 2015. Medical marijuana: is the cart before the horse? Jama, 313, 2431-2432.

Medical marijuana?

Public Policy Public Health

Law Medicine

Alcohol + Cannabis • Alcohol impairs

• Thinking

• Planning

• Reaction time

• Multitasking

• So the driver relies on habit

• Cannabis impairs

• Habituated responses

So the driver relies on thinking

0

10

20

30

40

50

60

70Ogden et al. (n=1809)

Ogden, E., et al., The relationship between accident culpability and presence of drugs in blood from injured Victorian drivers., in 19th International Council on Alcohol Drugs and Traffic Safety. 2010: Oslo.

Conclusion

• We should not rely on Canada and USA for data

– We need more work on cannabis and impairment

– What about ‘medical marijuana’ impairment?

– All the work concentrates on THC. What about the 100+ other cannabinoids

• Should we measure THC-COOH?

– Validation of interpretation of levels

– How would that look in legislation?

Methamphetamine is a powerful CNS stimulant derived from ephedrine and closely related to adrenaline

• First synthetized 1919

• Patented 1920

Adrenaline

Ephedrine

Methamphetamine

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utp

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NAc shell

Empty

Box Feeding

Di Chiara et al., Neuroscience, 1999.

FOOD

Mounts Intromissions Ejaculations

Fiorino and Phillips, J. Neuroscience, 1997.

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% B

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)

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Sample

Number

1 2 3 4 5 6 7 8

SEX

Female Present

Natural rewards

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MORPHINE

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Time After Nicotine

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Accumbens Caudate

NICOTINE

Di Chiara and Imperato, PNAS, 1988

Effects of Drugs on Dopamine Release

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MORPHINE

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Time After Nicotine

% o

f B

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as

e

Accumbens Caudate

NICOTINE

Di Chiara and Imperato, PNAS, 1988

Effects of Drugs on Dopamine Release

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% o

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% o

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as

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0.5 1.0 2.5 10

Dose (mg/kg)

MORPHINE

0

100

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250

0 1 2 3 hr

Time After Nicotine

% o

f B

as

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as

e

Accumbens Caudate

NICOTINE

Di Chiara and Imperato, PNAS, 1988

Effects of Drugs on Dopamine Release

Methamphetamine

ABEKAWA, T., OHMORI, T. & KOYAMA, T. 1994. Effects of repeated administration of a high dose of methamphetamine on dopamine and glutamate release in rat striatum and nucleus accumbens. Brain research, 643, 276-281.

Amphetamines

• Low doses

– Improve concentration

– Reduce fatigue

– Improve driving (esp. with ADD)

• High doses

– Brain overload

– Tunnel vision

– Psychosis

Amphetamine misuse

• Withdrawal

– Fatigue

– Sudden onset of sleep

• Abuse

– Cyclic pattern of use

• Intoxicated

• Crash

– Psychosis

Opiates and opioids

The medical opioid epidemic

Oxycodone in Victoria

HUXTABLE, C. A., J ROBERTS, L., SOMOGYI, A. & E MACINTYRE, P. 2011. Acute pain management in opioid-tolerant patients: A growing challenge.

Goulburn Valley Alcohol and Drug Service

Addiction is not tolerance or dependence

• Addiction is compulsive drug seeking knowing

the negative health and social consequences

• Tolerance is a consequence of neuroadaption

and is almost invariable long term

• Dependence result in withdrawal syndrome

Goulburn Valley Alcohol and Drug Service

Addiction is NOT simply bad patient choices

• Addiction can be the result of bad doctor choices

– High doses

– Long-acting formulation

– Combination of opioids with benzodiazepines

– Long-term use (> 3 months)

– Not recognising substance-use disorder

– Adolescence

Goulburn Valley Alcohol and Drug Service

The risk of addiction in acute pain

• The likelihood of chronic opioid use increases with each additional day of medication supplied starting with the third day

• Sharpest increase occurs after the fifth day

Volkow, N. D. and A. T. McLellan (2016). "Opioid abuse in chronic pain—misconceptions and mitigation strategies." New England Journal of Medicine 374(13): 1253-1263.

Goulburn Valley Alcohol and Drug Service

Avoid too many tablets on discharge

Shah, A., Hayes, C. J., & Martin, B. C. (2017). Characteristics of initial prescription episodes and likelihood of long-term opioid use-United States, 2006-2015. MMWR. Morbidity and mortality weekly report, 66(10), 265-269.

N=1,294,247

Goulburn Valley Alcohol and Drug Service

Do not authorise repeats

Shah, A., Hayes, C. J., & Martin, B. C. (2017). Characteristics of initial prescription episodes and likelihood of long-term opioid use-United States, 2006-2015. MMWR. Morbidity and mortality weekly report, 66(10), 265-269.

Opiate Replacement Therapy

• Methadone • No difference in traffic violation rate

• No difference in accident rate

• Infrequent in fatal drivers - 0.1%

Stout, P.R. and L.J. Farrell, Opioids-Effects on human performance and behavior. Forensic Science Review, 2003. 15(1): p. 29-58.

• Buprenorphine

• Less impairment than methadone

Soyka, M., et al., Less driving impairment on buprenorphine than methadone in drug-dependent patients? Journal of Neuropsychiatry, 2001. 13(4): p. 527-528.

Assessing fitness to drive

• Australian national standard on opiates • … Cognitive performance is reduced early in treatment, largely due to their

sedative effects, but neuroadaptation is rapidly established. This means that patients on a stable dose of an opioid may not have a higher risk of a crash. This includes patients on buprenorphine and methadone for their opioid dependency, providing the dose has been stabilised over some weeks and they are not abusing other impairing drugs. …

Assessing Fitness to Drive for Commercial and Private Vehicle Drivers. 2012, AustRoads: Canberra.

• Impairment reflects the OTHER DRUGS TAKEN not the ORT!

Tranquilisers

• 2 to 5% of Australians used a tranquiliser in the past 2 weeks

• Anxiety

• Insomnia

• Muscles relaxant

• Epilepsy

• Intoxication

• Often used with other drugs

• 23 tablets/year for every person over 15 years old in Australia

Benzodiazepines

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184 (10.2%) drivers tested positive for a benzodiazepine

83.7% responsible for or contributed to collision

94

% r

esp

on

sib

le

Ogden, E., et al., Responsibility for non-fatal collision: the abuse of benzodiazepines, in 20th International Conference on Alcohol, Drugs and Traffic Safety (T2013), 2013, Brisbane, Queensland, Australia. 2013.

What is the value of adding warning labels?

• Labelling promotes responsible use of medicine • Informed decision making

• Understanding and management of risk

• Poor labelling has unintended consequences

• “Do not drive” = stop medicine

• “Avoid alcohol’ = stop medicine

NIVEAU 1

Soyez prudent

Ne pas conduire sans avoir

lu la notice

NIVEAU 2

Soyez très prudent

Ne pas conduire sans l’avis

d’un professionnel de santé

NIVEAU 3

Attention, danger :

Ne pas conduire

Pour la reprise de la conduite,

demandez l’avis d’un médecin

NIVEAU 1

Soyez prudent

Ne pas conduire sans avoir

lu la notice

NIVEAU 2

Soyez très prudent

Ne pas conduire sans l’avis

d’un professionnel de santé

NIVEAU 3

Attention, danger :

Ne pas conduire

Pour la reprise de la conduite,

demandez l’avis d’un médecin

Schulze, H., et al., Driving under the influence of drugs, alcohol and medicines in Europe—findings from the DRUID project. 2012, European Monitoring Centre for Drugs and Drug Addiction.

ICADTS Working Party on medication and driving

2

L E V E L 1

Be careful

Do not drive without

having read the notice

L E V E L 2

Be very careful

Do not drive without the

advice of a health

professional

L E V E L 3

Attention, danger :

do not drive

Before returning to the wheel,

seek the advice of a doctor

L E V E L 1

Be careful

Do not drive without

having read the notice

L E V E L 2

Be very careful

Do not drive without the

advice of a health

professional

L E V E L 3

Attention, danger :

do not drive

Before returning to the wheel,

seek the advice of a doctor

SafeScript

Is real time prescribing information possible nationally?

Guidelines define remission as

• Abstinence from use of impairing substance/s

• Reduced frequency of use - unlikely to cause impairment

• Confirmed by biological monitoring for presence of drugs

Oxford Dictionary defines remission as

• A temporary diminution of the severity of disease or pain

Remission

Applicants are highly motivated to under-report use

• Minimise perception of problems

• Maximise chance of licence

Self report is unreliable at best

• Meta-analysis - 42% reported use when drugs were found on test

Is ‘remission’ genuine?

Which matrix for testing?

BLOOD

ORAL FLUID

URINE

SWEAT

HAIR & NAILS

Minutes Hours Days Weeks Months Years

MATRIX HAIR BLOOD URINE

Collection

Non-invasive

Easy to transport

Easy to collect

Invasive

Biohazard

Requires refrigeration

Non-invasive

Transport issues

Requires refrigeration

Adulteration

Detection

Window > 3 days to 6 months 1 – 2 days 2 hours to a week

Which matrix?

Urine

Easy to collect

Non-invasive

Cheap to analyse

Cheating …

Devices and artificial urine

Hair is the obvious choice

• Four ways to beat a hair follicle drug test

– Shave it all off

– A new industry

• “Detox products that work”

• “Personalized detox program”

• Do-it-yourself detox

but …

Clinical tests are crude

• Mini-mental state

• MoCA useful

Specialised test batteries sensitive but time consuming

• Vienna Test Battery (Schufreid)

• CANTAB (Cambridge Automated Neuropsychological Test Battery)

• CDR – Computerised assessment system

Absence of cognitive impairments

69

Driving

Simulated driving

• Safer

• No agreed standards

On-road assessment

• Inherent risk

• Requires skilled assessor

Medical & psychological assessment

Knowledge

Insight

Understanding

Change

Positive assessment Licence back

Getting it right

FIT TO DRIVE UNFIT TO

DRIVE

ABSTINENT

WRONG

DRUG USER

WRONG

Precision = true positives as percentage of positives Accuracy = percentage correctly classified

Ogden, E. J. D., et al. (2018). "When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national

guidelines." Internal Medicine Journal 48(8): 908-915.

Principles for better outcomes

Safety at work is not optional

Drug-impairment is just as important as alcohol-impairment

Professionals can help responsible workers to remain safe

They can identify problems by seeking them out

We must offer long term treatment for those who need it