Bill Anderson PhD FABFT Issues to be Discussed What can toxicologists tell you about your results Cannabis Issues Opiates Issues Benzodiazepines Issues Designer Drugs Issues Toxicologists Testimony1 ID: 544870
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Interpretation Issues with Blood Results for marijuana, opiates, designer drugs, and other therapeutic and illicit drugs
Bill Anderson, PhD, F-ABFTSlide2
Issues to be DiscussedWhat can toxicologists tell you about your results?Cannabis IssuesOpiates IssuesBenzodiazepines Issues
Designer Drugs IssuesSlide3
Toxicologists Testimony_1Typical QuestionsWhat drugs are present?How do the detected drugs affect an individual?Therapeutic effects, if any, maybe multipleIf impairing, signs/symptoms of impairment
What was the concentration of the drugs?Is the concentration high or lowIs it a therapeutic concentration I was once asked what is a normal concentration of heroin – Answer was zeroIs concentration impairingSlide4
Toxicologists Testimony_2If multiple drugs are present would they be additive, synergistic, or would they cancel each other out?If methamphetamine and heroin taken together would they mitigate the response of each other?Actually may modify DRE observations. How about tolerance?
Do impairing affects disappear with long term use?Was a new drug recently added or was a dose recently increased?Slide5
What a toxicologist can really say about drugsAll of the abovePart of the aboveNone of the aboveDepends not only on toxicologist but what information is availableSometimes the best toxicologist in the world cannot offer opinions without
support informationDriving patternSFST’s and/or DRESlide6
CannabisProbably the most challenging drug we have to deal with today- why?Pharmacokinetics and pharmacodynamics of THCDifferences in action of THC on individualsDose from same cigarette may vary tremendously
Higher percentage of THC in newer marijuanaEach user can titrate their dosePresence of other drugs – especially small amounts of alcoholToleranceChronic vs occasional vs novice smokersSlide7
Major Issue with CannabisTrying to make it fit the alcohol model of intoxicationSlide8
Marijuana (Cannabis)Active ingredient Delta-9-Tetrahydrocannabinol (THC)Major Metabolites11-nor-9-carboxy-delta-9-tetrahydrocannabinol
Major Metabolite Only analyte detected in urineInactive11-hydroxy-delta-9-tetrahydrocannabinolActiveConcentration low; not measured in some labs, may become an issue with oral THCSlide9
Very different from alcoholDefies category of impairmentCNS stimulationCNS depressantHallucinogenRoutes of administration SmokingMain route for abused marijuanaMedical Marijuana may be smoked in some states
OralHash brownies, Marinol®, Sativex (oral spray) THCSlide10
Two distinct receptors identifiedCB1 (central), CB2 (peripheral) Both act like anandamide, an endogenous cannabinoid that is involved with:Control of locomotion, Emotional behavior, Cognitive function, Cardiovascular responsePain, Feeding behavior, Addiction
Also acts at dopamine receptorsPleasure, reward systemsTHC- Mechanism of ActionSlide11
EuphoriaRelaxationAltered time perceptionLack of concentrationImpaired learningImpaired memory, especially short term memoryMood changesPanic reactions, hallucinations
Behavioral Effects of THCSlide12
Increase in heart rateConjunctival suffusion (red eyes)Dry mouth and throatIncreased appetiteHypotension and dizzinessLack of convergenceMost behaviors return to baseline within 3-8 hours
Some impairment reported as far out as 24 hours after drug intakePhysiological Effects of THCSlide13
Smoking a Single Cigarette 3.55 % THCSlide14
Smoking a Single Cigarette 3.55 % THCSlide15
THC PharmacokineticsTHC very lipophilic (fat soluble) moleculeTwo phases of eliminationRedistribution (t1/2 short – few hours)
Terminal elimination (t1/2 long – up to 48 hours)THC goes into fat cellsLeaches out slowly (rate limiting step for elimination)Metabolized immediately upon leaving fat depotsExplains why THCCOOH can be detected so long in the urine.Slide16
Smoking a Single Cigarette 3.55 % THCSlide17
Smoking a Single Cigarette 3.55 % THCSlide18
Smoking a Single Cigarette 3.55% THCCasual and Chronic SmokerSlide19
Study of Karschner et alAddiction. 2009 December; 104(12): 2041–2048Twenty-five long term frequent cannabis users studied for 7 days of monitored abstinence
9 had no measured THCOn day #7, 3 had values ≥ 1.0 ng/mL3.0 ng/mL – 4 blunts/day1.0 ng/mL – 8 blunts/day2.2 ng/mL – 4 blunts/day
All with positive results were female
Results not correlated with body mass index
Were they impaired?Slide20
Effects have been studied primarily by three methods:Epidemiological studiesOdds ratio for potential to be killed in MVAOdds ratio for culpability of causing a non-fatal crashObservations of impairment in multiple studies of arrested driversVarious laboratory test that are markers for impairmentDriving studies
On-roadSimulatorsTHC and DrivingSlide21
General Facts about THCIn Northern Nevada, more than half of THC concentrations in DUID cases are between 2-5 ng/mL.For casual smoker, THC is <2
ng/mL within 3-4 hours.Major effects of THC last for 4-6 hours, depending upon whom you believe.Impairment for pilots on highly complex task reported after 24 hours.Slide22
There is no proven relationship between THC concentration and impairment.THC drops so rapidly, it is impossible to know what specimen concentration was at the time of driving.Recent study from Australia, Papafotiou et al.THC = 6.2-13.8
ng/mL@ 30 min after smoking with significantly less impairment than at 55 min when THC = 3.2-5.1 ng/mL.How can we explain that?Does THC in CNS peak later than it does in the blood?No correlation of urine with much of anything except use General Facts about THC - 2Slide23
Tolerance to some THC effects can occur with heavy smokingTolerance does NOT develop with all measures of impairmentBig argument in literature about just how much tolerance does developCognitive deficits have been observed in chronic smokers for as long as 21 days.Big debate about degree of impairment exists in chronic smokers
General Facts about THC - 3Slide24
Oral THC disposition very different than smoked THCTHC peaks at 120 min and concentration is low 3-7 ng/mL up to19 ng/mLActive hydroxy
metabolite ≥ than THC, tmax after THCGeneral Facts about THC - 4Slide25
Two drugs that impair ability to drive by acting on multiple receptorsWould expect at least additive affectsMany researches report a synergistic effectMultiple studies have demonstrated this phenomenonSignificant impairment seen with low doses of alcohol (0.04 g/100mL)THC Plus AlcoholSlide26
Testimony Last WeekTHC 8.7 ng/mLTHCCOOH 19 ng/mLIssuesDoes THC impair driving?Does THC increase crash risk?Does THC sometimes improve driving?
Was this a recent smoking?Was subject a chronic smoker?Do SFST’s and/or DRE work for THC?Was he impaired?Slide27
Opiates and OpioidsMajor issuesDose can vary tremendously from person to personTherapeutic concentration of methadone can be from 50 ng/mL up to 800 ng/mL or higherHigh dose pain patients can have concentrations of any opiate that would kill naïve users
Tolerance develops for almost all opiatesTolerance can be lost or greatly diminished with only one day of abstinenceDo pharmacokinetic calculations allow toxicologist to estimate expected concentration after dosing?Slide28
Opiates – The Good NewsNon impaired individuals are not or do not:Slow and lethargicSleepy and “on the nod”Fail SFST’sThey will have pin-point pupilsGood officer observations and articulation is paramount to making a case.Slide29
Benzodiazepines/Carisoprodol and Z Drugs (zolpidem, zopiclone, zaleplon)Therapeutic concentrations known for most conditions, but can vary widelyOften prescribed with other CNS depressants and/or opiatesTolerance does developIf severely impaired have look and feel of alcohol intoxication
For Z-Drugs, I am often asked if the concentration is therapeutic. It often is, but what are these drugs used for?Slide30
People have a right to drive with prescribed drugs.They do not have a right to drive while impaired by prescribed drugs.Slide31
Designer DrugsLab may not have standardsNo pharmacological or pharmacokinetic studies performed.Concentration in blood may not be availableIf it is, we might not know what it meansAs soon as designer drugs are made illegal, users switch to something new
Current favorites are ethylone and butylone, U-47700, designer fentanyls at least until tomorrowSlide32
What Does it Take to Identify Drugged DriverObservant and articulate arresting officerDRE exam is a great helpCompetent laboratory analysisDA awareness of issues with drugged drivingCompetent toxicology testimony