1 Driving under the influence of drugs – the scientific evidenceKim Wolff Professor of Addiction Science King’s College London Drug Driving 2016 KW (c)

2 2011 UK Government agreed to implement recommendations from the North Report Government’s 2011 Framework for Road safety “…We will explore the case for introducing an offence of having a specified drug in the body while driving, in addition to the current offence of driving whilst impaired by drugs…..”   Drug Driving 2016 KW (c)

3 LEVEL of RISK rather than IMPAIRMENTOur APPROACH did not seek to define, measure or proportion a drug level to a certain degree of impairment Legislation already in place for driving whilst impaired Where a test is employed to judge a drivers level of impairment at the road-side: used in England and Wales, Road Traffic Act Section 4 (UK Government, 1988) In terms of our ToR defining impairment for different classes of drugs too complicated Impairment differs for different classes of drugs: (stimulants Vs depressants Vs hallucinogens) There is no universal agreement on how to measure impairment

4 CANNABIS SEVERAL KEY FACTS FOR Δ9- TETRA HYDROCANNABINOL (THC): In UK adults (16 to 59 yrs.) who reported drug-driving with illegal drugs (once or twice in the last 12 months) Cannabis as elsewhere is most commonly used illicit drug in drivers Significant dose related decrement in driving performance (observed in experimental, real-life, simulator, laboratory and Forensic Traffic Data): Higher dose – the worse you drive! Raised THC blood concentration are significantly associated with increased risk of Traffic Crash and serious or fatal crash risk Meta-analysis shows mean blood concentration >3.7µg/L impairs individuals to a degree comparable to blood alcohol levels 50mg/100mL blood. Drug Driving 2016 KW (c)

5 CANNABIS - 2 CANNABIS USE BEHAVIOUR Smoking a single cannabis cigarette infrequently (recreational use): higher conc THC (21 µg/L µg/L) causing acute intoxication In chronic, daily or near daily use over a prolonged period (years), steady-state concentrations of THC ranging between 1 µg/L to 6.4 µg/L Blood concentrations are maintained by sequestration of the drug from the tissues: falling to <1 µg/L after 24 hours abstinence and <0.5 µg/L after 7 days abstinence. Passive exposure to cannabis smoke leads to very low levels of THC: less than 1 µg/L; There is clearly a case for cannabis. Drug Driving 2016 KW (c)

6 CANNABIS – RISK OF RTC Meta-analysis of over 120 studies: the higher the conc THC in blood, the greater the driving impairment; Significant increased crash risk when THC in the blood was ≥ 5 µg/L, whether or not ingestion had occurred recently and regardless of the origin of the drug (medicinal or illicit) Wolff & Johnston, 2013 Individuals who drive within 2 hours of using cannabis have raised rates of collision. Drivers consuming cannabis 2 or 6 times more likely to be at risk RTC. Indeed the risk of a driving accident was increased by 16 times when cannabis and alcohol were consumed concurrently by drivers Possible need to look at alcohol in combination with cannabis Drug Driving 2016 KW (c)

7 Drug Driving 2016 KW (c)

8 Medicinal cannabinoidsMedicinal cannabinoids, providing they are taken in accordance with directions given by the prescriber, produce low steady-state blood concentrations of THC (about 1 μg/L to 2 μg/L). This is because the amount of THC prescribed is very low: Nabilone (Cesamet®) is prescribed in doses ranging from 2mg to 6mg/day Nabiximols (Sativex®), an oromucosal spray containing THC together with cannabidiol (CBD) is delivered in a fixed dose of 2.7 mg THC and 2.5 mg CBD. Drug Driving 2016 KW (c)

9 WHICH Amphetamine? Scientific data largely refers to amphetamine, methamphetamine and MDMA (often combined) Methamphetamine breaks down in the body into amphetamine UK does not see methamphetamine too often Amphetamine prescribed in drug treatment settings and for Attention Deficit Hyperactivity Disorder (ADHD) Seligiline, clobenzorex, famprofazone, fencamine, furfenorex and prenylamine (amphetamine metabolite) Other stimulants: Mephedrone, BZP, cathinone, etc - little data about these substances since laboratories do not routinely screen for them Drug Driving 2016 KW (c)

10 Amphetamine and sleep Sleep deprivation Amphetamine and sleepAmphetamine increases alertness, risk taking, suppresses sleepiness and tiredness for up to 6h after dosing After 6h feel restless, over- active and fatigued: Characterised by sleeplessness Considered by DRUID researchers to be equivalent to 50 mg alcohol/100 ml Blood 10-40 mg amphetamine did not compensate for poor driving produced by sleep deprivation (Hjalmdadhl et al, 2012) Amphetamine and sleep Drug Driving 2016 KW (c)

11 Evidence regarding amphetamineAmphetamine and impairment Drivers apprehended under influence of amphetamine No evidence of impairment at low doses amphetamine: small doses used by military to maintain concentration/wakefulness At therapeutic doses plasma conc not usually more than 200 ug/L Mean conc in UK 496 ug/L to 651 ug/L Time lag between blood collection and accident about 2h Fatigue after amphetamine use may be a factor Evidence regarding amphetamine Drug Driving 2016 KW (c)

12 The Evidence for Driving riskAlthough amphetamine less prevalent ORs are higher for risk of RTC following consumption than either cannabis or cocaine Amphetamine 4.46 (p<0.05) Meta analysis of 8 laboratory studies analysing presence of amphetamines in drivers fatally injured in road crashes Amphetamine 8.88 (p<0.001) Case control study (Thailand) comparing urine methamphetamine Methamphetamine 8.35 ( ) Dutch RTCs Drug Driving 2016 KW (c)

13 COCAINE OR suggest 3 times at risk of being seriously injured if use cocaine and drive Driving whilst sleep deprived following cocaine binge also been reported as problem Analytical issues as cocaine fast acting drug Would all dangerous driving be captured by screening for cocaine alone? Should benzoylecgonine (BZE) the main metabolite be considered as well? Should a threshold be set for cocaine alone, Cocaine and BZE or even BZE alone Alcohol use and cocaine also a concern Drug Driving 2016 KW (c)

14 COCAINE Substance OR CIs Basis of the ORCocaine (p<0.05) Meta analysis of 4 studies analysing presence of cocaine in drivers fatally injured in road crashes Cocaine Analysis of blood samples collected from individuals seriously injured in RTAs in 6 European countries between Cocaine Dutch Case-control study comparing 110 drivers hospitalised after a RTA Drug Driving 2016 KW (c)

15 MARCH 2015 new LEGISLATION SUMMARY – SO FARA new offence of driving with certain specified controlled drugs* in excess of specified WHOLE BLOOD concentration in the body came into force during March 2015. This offence is an addition to the existing rules on drug impaired driving and fitness to drive. The legislation also provides for a statutory “medical defence” for this new offence, for patients taking their medicines in accordance with instructions. Controlled drugs are defined in the Misuse of Drugs Act 1971 Strict liability offence: Fine, lose license, prison MARCH 2015 new LEGISLATION Drug Driving 2016 KW (c)

16 CUT-OFFS for illicit drugs in BLOODRISK based EXPERT PANEL Low level detection QUANTIFicATION (LLOQ) LEGISLATION THC ug/L Cocaine ug/L BZE ug/L Methylamphetamine 200 ug/L MDMA ug/L Ketamine ug/L LSD 6-MAM THC ug/L Cocaine ug/L BZE ug/L Methylamphetamine 10 ug/L MDMA ug/L Ketamine ug/L LSD ug/L 6 MAM ug/L CUT-OFFS for illicit drugs in BLOOD Drug Driving 2016 KW (c)

17 OTHER APPROACHES Some countries have instigated a programme of zero tolerance Equates to a complete ban on the use of a specified drug whilst driving Another approach is often referred to as the ‘per se’ approach Based on the detection of a drug in a driver above a defined cut-off concentration predominantly in whole blood Cut-off concentrations often been linked to risk and driver safety. Drug Driving 2016 KW (c)

18 PRESCRIBED CONTROLLED DRUGSAlso included in the legislation Controlled Drug - this is a legal definition and refers to those drugs that are controlled under the 1971 Act - this regulates the import, export, possession, supply, and other aspects of activities relating to those drugs specified in the 1971 Act. Drug Driving 2016 KW (c)

19 BENZODIAZEPINES: SEDATIVES/ ANXIOLYTICSBZ used more in the UK than in Europe by driving population. In Europe women aged 35+, day-time drivers DRUID 2-5 times risk RTC compared no BZ First 2-4 weeks of prescription Anxiolytics: Diazepam, Lorazepam and Oxazepam OR: 2.5 to 5.5 having an accident severe enough to require hospitalisation Benzodiazepine/driving collaboration group. BZ and Alcohol OR: 2.00 (alcohol alone g/L) OR: 7.00 (alcohol >0.2g/L + BZ ) Drug Driving 2016 KW (c)

20 BENZODIAZEPINES: SEDATIVES/ANXIOLYTICSDRUID among killed drivers: benzodiazepines was the second most frequent toxicological finding after alcohol (DRUID, D2.2.5, 2012, WOMEN AGED 35+, DAY-TIME DRIVERS) Benzodiazepine deleterious driving behaviour in the older patient when longer-acting and larger quantities of benzodiazepines were consumed. RTC victims aged ≥60 years, benzodiazepines use were associated with a significantly greater risk of a crash (OR:5.3,3.6–7.8,p<.001): Older patients were between 4-6 fold more likely to be hospitalised following a RTC than others in the same age group not prescribed benzodiazepines   Drug Driving 2016 KW (c)

21 DRIVER RISK WITH MEDICATION: SEDATION OR ANTI-ANXIETYBENZODIAZEPINES AND Z-DRUGS Impairment in apprehended drivers in Norway *Adjusted for all background variables Bramness et al, 2002 Diazepam OR: 1.61 (n=/411;P Oxazepam OR: 3.65 (n=/73; P Flunitrazepam OR: 4.11 (n=/211;(P UK study, Tayside police 19, 386 drivers involved first RTA: Barbone et al Lancet, 1998 Zopiclone alone OR: 4.00 (1.31 – 12.2) Any BZ with positive breath test OR; 8.15 ( ) Drug Driving 2016 KW (c)

22 PRESCRIBED MEDICATION: PAIN RELIEFOPIOIDS usually mean Morphine, Methadone and Diamorphine together Acknowledged in Europe that Opiates/opioids increases risk RTA between 2-10 times Medicinal opioids seem to have higher risk than illicit use Over-the-counter medicine (codeine) little risk if taken as prescribed ANY Opiate/Opioid or BZ with any amount of alcohol significantly increases risk of RTA Drug Driving 2016 KW (c)

23 DRIVER RISK and PAIN RELIEF MEDICATIONOpiates, Opioids, Medicinal opioids: Odds individuals seriously injured in RTCs in 6 European countries when consumed Illicit opiates (heroin/morphine) OR ( ) . Odds individuals being killed in road accidents in 4 European countries between who consumed Illicit opiates OR ( ) Odds individuals being seriously injured in RTCs in 6 European countries who consumed Medicinal opioids (methadone/diacetylmorphine/morphine) OR 9.06 ( ) Odds individuals killed in RTCs in 4 European countries between who consumed Medicinal opioids OR 4.82 ( ) Drug Driving 2016 KW (c)

24 METHADONE Decided to set threshold high 500 ug/L Doses 80 mg and aboveLiterature mixed about the impact of methadone on driving Use of other drugs Blood concentrations between 90 ug/L and 132 ug/L drivers successfully passed driving test At high concentrations reaction time and decision time decreases Decided to set threshold high 500 ug/L Doses 80 mg and above BUT use any methadone with alcohol risk RTC increases Need to report to DVLA glancewww.gov.uk/government/publications/at-a-glance 200, 000 M patients 3% known to DVLA Drug Driving 2016 KW (c)

25 PRESCRIBED CONTROLLED DRUGS in BLOODExpert panel LEGISLATION Methadone 500 ug/L Amphetamine 600 ug/L Morphine 80 ug/L Diazepam ug/L Oxazepam 300 ug/L Flunitrazepam 300 ug/L Clonazepam 50 ug/L Lorazepam 100 ug/L Temazepam ug/L Methadone 500 ug/L Amphetamine 250 ug/L Morphine 80 ug/L Diazepam ug/L Oxazepam 300 ug/L Flunitrazepam 300 ug/L Clonazepam 50 ug/L Lorazepam 100 ug/L Temazepam ug/L PRESCRIBED CONTROLLED DRUGS in BLOOD Drug Driving 2016 KW (c)

26 Medical Defence Drugs proscribed for driving can be used legitimately, in accordance with medical advice (CANNABIS for multiple sclerosis). Recognised may be more dangerous for a person to drive not having taken their prescribed medication than driving having taken it. The legislation not expected to affect those who are properly and safely taking medically prescribed drugs and driving in accordance with medical advice, and for whom, there is no evidence of driving in an unsafe way. A statutory defence is available for a driver who has taken a drug supplied or prescribed for medical purposes and who has taken the drug in line with directions and instructions. (This is included in Clause 27 of the Crime and Courts Bill) Drug Driving 2016 KW (c)

27 ADVICE……… It was deemed helpful for patients to keep some suitable evidence with them when they are driving that  provides medical confirmation of drug they are taking (the controlled drug) as a medicine prescribed or supplied by a healthcare professional  and taken in accordance with the leaflet accompanying the medicine, in case that patient was ever stopped by the police.  Drug Driving 2016 KW (c)

28 ALCOHOL and DRUG use Significant risk with multiple drug useAlcohol use multiplies risk How do we deal with this? Evidence of risk for Alcohol and drugs combined DRUID (2012) OR seriously injured RTC ( ) Drug Driving 2016 KW (c)

29 MULTIPLE DRUG USE Significant risk with multiple drug useApproximately 6 times more risk of a RTC if using multiple drugs compared with no drug OR: 6.05 (95% CI: ) If combine more than one drug with alcohol the risk of a RTC substantially increases and was estimated to be more than 100 times as risky as using no drugs at all Drugs + alcohol compared with no drugs OR: 112 (95% CI: ) Movig et al, 2004 Drug Driving 2016 KW (c)

30 In PRACTICE Stopped by police for driving offence Breathalysed firstThen drug screen. Oral Fluid (saliva test) – only test for cannabis or cocaine at moment If deemed unfit or impaired or positive Blood sample at Police Station will test for all 17 drugs Image – In PRACTICE Drug Driving 2016 KW (c)

31 At present Blood is the only matrix that can be used as evidence in a court of law to confirm drug use Scientific evidence is concerned with Blood (urine not suitable) Oral Fluid being discussed as a confirmatory matrix but evidence is not conclusive especially drugs contaminated by nasal use (heroin, cocaine, cannabis) Approach in UK – screening device at road side based on immunoassay using Oral Fluid, then confirmatory blood test at police station The time lap between blood sample collection and receipt by laboratory is vital (<2 hrs) Chain of custody important: tamper proof drug test kits; standardised preservatives Accreditation of laboratory essential BIOLOGICAL SAMPLES Drug Driving 2016 KW (c)

32 DRINK-DRIVE PENALTIESBeing in charge of a vehicle while above the legal limit or unfit through drink You may get: 3 months’ imprisonment; up to £2,500 fine a possible driving ban Driving or attempting to drive while above the legal limit or unfit through drink You may get: 6 months’ imprisonment; an unlimited fine a driving ban for at least 1 year (3 years if convicted twice in 10 years) Refusing to provide a specimen of breath, blood or urine for analysis a ban from driving for at least 1 year Causing death by careless driving when under the influence of drink You may get: 14 years’ imprisonment; an unlimited fine a ban from driving for at least 2 years; an extended driving test before your licence is returned ;

33 Penalties for drug driving If you’re convicted of drug driving you’ll get: a minimum 1 year driving ban an unlimited fine up to 6 months in prison a criminal record Your driving licence will also show you’ve been convicted for drug driving. This will last for 11 years. Drug Driving 2016 KW (c)

34 Ketamine: Growing evidenceCSEW: subjects notified for driving under the influence suggested 40% previous experiences of ketamine intake, either alone or in combination with other drugs 2012, 13 out of 853 oral fluid specimens taken from random roadside testing in Victoria were found positive for ketamine (Chu et al, 2012). More recently, 14 of 376 suspected cases of driving under the influence were reported to be ketamine-positive individuals (Birch et al, 2013). In this UK study, ketamine was not included in the standard panel and was assessed only if suspected. The mean and median concentrations of KET detected in those cases were 421 and 385 ng/mL, respectively, and the mean and median concentrations of norketamine, the main metabolite, were 605 and 410 mg/mL, respectively. Another survey (Bezemer et al, 2014) found that 10 of blood samples collected from impaired drivers were KET-positive. Two further studies reported 45% KET positivity among intoxicated drivers involved in non-fatal traffic accident (Wong et al, 2012) and 9% positivity among those involved in fatal crashes (Cheng et al, 2005) Drug Driving 2016 KW (c)

35 KETAMINE Driving under the influence of ketamine (Cheng 2007)Hong Kong 62 volunteers exiting from a dance-event 39 had ketamine detected with in oral fluid. 21 (54%) had only used ketamine Others used MDMA, benzodiazepines and/or THC) 15 successfully identified by FIT Impairment greatest concentration >300 ug/L. Clinical reports (Weiner et al, 2000) “Moderate” to “extreme” disturbance of perceptions at 200 ug/L KETAMINE Drug Driving 2016 KW (c)

36 ACKNOWLEDGEMENTS Expert Panel on Drug Driving: Roger Brimblecombe, Colin Forfar, A. Robert Forrest, Eilish Gilvarry, Judith Morgan, M. David Osselton, Lily Read, David Taylor, and Atholl Johnston REFERENCES https://www.gov.uk/government/publications/driving-under- the-influence-of-drugs--2 driving-limits/ ACKNOWLEDGEMENTS Drug Driving 2016 KW (c)

37 ANY QUESTIONS THANK YOU Drug Driving 2016 KW (c)