Post on 19-Oct-2019
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
0
50
100
150
200
250
300
350
400
0 0.05 0.1 0.15 0.2
BAC
Re
lati
ve R
isk
. . .
How much matters?
If you can measure the alcohol there is an effect
How many drinks for your pilot ?
0
10
20
30
40
50
60
70
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
4
6
8
10
12
14
16
18
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
2
3
4
5
6
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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0 60 120 180
Time (min)
% o
f B
as
al D
A O
utp
ut
NAc shell
Empty
Box Feeding
Di Chiara et al., Neuroscience, 1999.
FOOD
Mounts Intromissions Ejaculations
Fiorino and Phillips, J. Neuroscience, 1997.
100
150
200
DA
Co
nc
en
tra
tio
n (
% B
as
eli
ne
)
15
0
5
10
Co
pu
latio
n F
req
uen
cy
Sample
Number
1 2 3 4 5 6 7 8
SEX
Female Present
Natural rewards
0
100
200
300
400
0 1 2 3 4 5 hr Time After Cocaine
% o
f B
as
al R
ele
as
e
DA
Accumbens COCAINE
0
100
150
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250
0 1 2 3 4 5hr Time After Morphine
% o
f B
as
al R
ele
as
e Accumbens
0.5 1.0 2.5 10
Dose (mg/kg)
MORPHINE
0
100
150
200
250
0 1 2 3 hr
Time After Nicotine
% o
f B
as
al R
ele
as
e
Accumbens Caudate
NICOTINE
Di Chiara and Imperato, PNAS, 1988
Effects of Drugs on Dopamine Release
0
100
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800
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1000
1100
0 1 2 3 4 5 hr
Time After Amphetamine
% o
f B
as
al R
ele
as
e
DA
Accumbens AMPHETAMINE
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400
0 1 2 3 4 5 hr Time After Cocaine
% o
f B
as
al R
ele
as
e
DA
Accumbens COCAINE
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250
0 1 2 3 4 5hr Time After Morphine
% o
f B
as
al R
ele
as
e Accumbens
0.5 1.0 2.5 10
Dose (mg/kg)
MORPHINE
0
100
150
200
250
0 1 2 3 hr
Time After Nicotine
% o
f B
as
al R
ele
as
e
Accumbens Caudate
NICOTINE
Di Chiara and Imperato, PNAS, 1988
Effects of Drugs on Dopamine Release
0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
Time After Amphetamine
% o
f B
as
al R
ele
as
e
DA
Accumbens AMPHETAMINE
0
100
200
300
400
0 1 2 3 4 5 hr Time After Cocaine
% o
f B
as
al R
ele
as
e
DA
Accumbens COCAINE
0
100
150
200
250
0 1 2 3 4 5hr Time After Morphine
% o
f B
as
al R
ele
as
e Accumbens
0.5 1.0 2.5 10
Dose (mg/kg)
MORPHINE
0
100
150
200
250
0 1 2 3 hr
Time After Nicotine
% o
f B
as
al R
ele
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
0
5
10
15
20
25
30
Od
ds
Ra
tio
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