1. Bill Anderson, PhD, F-ABFT
Interpretation Issues with Blood Results for marijuana, opiates, designer drugs, and other therapeutic and illicit drugs
Bill Anderson, PhD, F-ABFT

2. Issues to be Discussed
What can toxicologists tell you about your results?
Cannabis Issues
Opiates Issues
Benzodiazepines Issues
Designer Drugs Issues

3. Toxicologists Testimony_1
Typical Questions
What drugs are present?
How do the detected drugs affect an individual?
Therapeutic effects, if any, maybe multiple
If impairing, signs/symptoms of impairment
What was the concentration of the drugs?
Is the concentration high or low
Is it a therapeutic concentration
I was once asked what is a normal concentration of heroin – Answer was zero
Is concentration impairing

4. Toxicologists Testimony_2
If 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?

5. What a toxicologist can really say about drugs
All of the above
Part of the above
None of the above
Depends not only on toxicologist but what information is available
Sometimes the best toxicologist in the world cannot offer opinions without support information
Driving pattern
SFST’s and/or DRE

6. Cannabis
Probably the most challenging drug we have to deal with today- why?
Pharmacokinetics and pharmacodynamics of THC
Differences in action of THC on individuals
Dose from same cigarette may vary tremendously
Higher percentage of THC in newer marijuana
Each user can titrate their dose
Presence of other drugs – especially small amounts of alcohol
Tolerance
Chronic vs occasional vs novice smokers

7. Major Issue with Cannabis
Trying to make it fit the alcohol model of intoxication

8. Marijuana (Cannabis) Active ingredient Major Metabolites
Delta-9-Tetrahydrocannabinol (THC)
Major Metabolites
11-nor-9-carboxy-delta-9-tetrahydrocannabinol
Major Metabolite
Only analyte detected in urine
Inactive
11-hydroxy-delta-9-tetrahydrocannabinol
Active
Concentration low; not measured in some labs, may become an issue with oral THC

9. THC Very different from alcohol Defies category of impairment
CNS stimulation
CNS depressant
Hallucinogen
Routes of administration
Smoking
Main route for abused marijuana
Medical Marijuana may be smoked in some states
Oral
Hash brownies, Marinol®, Sativex (oral spray)

10. THC- Mechanism of Action
Two distinct receptors identified
CB1 (central), CB2 (peripheral)
Both act like anandamide, an endogenous cannabinoid that is involved with:
Control of locomotion, Emotional behavior,
Cognitive function, Cardiovascular response
Pain, Feeding behavior, Addiction
Also acts at dopamine receptors
Pleasure, reward systems

11. Behavioral Effects of THC
Euphoria
Relaxation
Altered time perception
Lack of concentration
Impaired learning
Impaired memory, especially short term memory
Mood changes
Panic reactions, hallucinations

12. Physiological Effects of THC
Increase in heart rate
Conjunctival suffusion (red eyes)
Dry mouth and throat
Increased appetite
Hypotension and dizziness
Lack of convergence
Most behaviors return to baseline within 3-8 hours
Some impairment reported as far out as 24 hours after drug intake

13. Smoking a Single Cigarette 3.55 % THC

14. Smoking a Single Cigarette 3.55 % THC

15. THC Pharmacokinetics THC very lipophilic (fat soluble) molecule
Two phases of elimination
Redistribution (t1/2 short – few hours)
Terminal elimination (t1/2 long – up to 48 hours)
THC goes into fat cells
Leaches out slowly (rate limiting step for elimination)
Metabolized immediately upon leaving fat depots
Explains why THCCOOH can be detected so long in the urine.

16. Smoking a Single Cigarette 3.55 % THC

17. Smoking a Single Cigarette 3.55 % THC

18. Smoking a Single Cigarette 3.55% THC Casual and Chronic Smoker

19. Study of Karschner et al Addiction. 2009 December; 104(12): 2041–2048
Twenty-five long term frequent cannabis users studied for 7 days of monitored abstinence
9 had no measured THC
On day #7, 3 had values ≥ 1.0 ng/mL
3.0 ng/mL – 4 blunts/day
1.0 ng/mL – 8 blunts/day
2.2 ng/mL – 4 blunts/day
All with positive results were female
Results not correlated with body mass index
Were they impaired?

20. THC and Driving Effects have been studied primarily by three methods:
Epidemiological studies
Odds ratio for potential to be killed in MVA
Odds ratio for culpability of causing a non-fatal crash
Observations of impairment in multiple studies of arrested drivers
Various laboratory test that are markers for impairment
Driving studies
On-road
Simulators

21. General Facts about THC
In 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 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.

22. General Facts about THC - 2
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 = min after smoking with significantly less impairment than at 55 min when THC = 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

23. General Facts about THC - 3
Tolerance to some THC effects can occur with heavy smoking
Tolerance does NOT develop with all measures of impairment
Big argument in literature about just how much tolerance does develop
Cognitive deficits have been observed in chronic smokers for as long as 21 days.
Big debate about degree of impairment exists in chronic smokers

24. General Facts about THC - 4
Oral THC disposition very different than smoked THC
THC peaks at 120 min and concentration is low 3-7 ng/mL up to19 ng/mL
Active hydroxy metabolite ≥ than THC, tmax after THC

25. THC Plus Alcohol
Two drugs that impair ability to drive by acting on multiple receptors
Would expect at least additive affects
Many researches report a synergistic effect
Multiple studies have demonstrated this phenomenon
Significant impairment seen with low doses of alcohol (0.04 g/100mL)

26. Testimony Last Week THC 8.7 ng/mL THCCOOH 19 ng/mL Issues
Does 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?

27. Opiates and Opioids Major issues
Dose can vary tremendously from person to person
Therapeutic concentration of methadone can be from 50 ng/mL up to 800 ng/mL or higher
High dose pain patients can have concentrations of any opiate that would kill naïve users
Tolerance develops for almost all opiates
Tolerance can be lost or greatly diminished with only one day of abstinence
Do pharmacokinetic calculations allow toxicologist to estimate expected concentration after dosing?

28. Opiates – The Good News Non impaired individuals are not or do not:
Slow and lethargic
Sleepy and “on the nod”
Fail SFST’s
They will have pin-point pupils
Good officer observations and articulation is paramount to making a case.

29. Benzodiazepines/Carisoprodol and Z Drugs (zolpidem, zopiclone, zaleplon)
Therapeutic concentrations known for most conditions, but can vary widely
Often prescribed with other CNS depressants and/or opiates
Tolerance does develop
If 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?

30. People have a right to drive with prescribed drugs.
They do not have a right to drive while impaired by prescribed drugs.

31. Designer Drugs Lab may not have standards
No pharmacological or pharmacokinetic studies performed.
Concentration in blood may not be available
If it is, we might not know what it means
As 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 tomorrow

32. What Does it Take to Identify Drugged Driver
Observant and articulate arresting officer
DRE exam is a great help
Competent laboratory analysis
DA awareness of issues with drugged driving
Competent toxicology testimony