Transcript PowerPoint - CLEAR Alliance

INTERPRETATION ISSUES WITH
BLOOD RESULTS FOR MARIJUANA,
OPIATES, DESIGNER DRUGS, AND
OTHER THERAPEUTIC AND ILLICIT
DRUGS
Bill Anderson, PhD, F-ABFT
Issues to be Discussed





What can toxicologists tell you about your
results?
Cannabis Issues
Opiates Issues
Benzodiazepines Issues
Designer Drugs Issues
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
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?
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
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
MAJOR ISSUE WITH
CANNABIS
Trying to make it fit the alcohol model of
intoxication
Marijuana (Cannabis)

Active ingredient


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
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)
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
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
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
Smoking a Single Cigarette
3.55 % THC
THC (ng/mL) - Plasma
300
250
200
150
100
50
0
0
1
2
3
4
Time (hrs)
5
6
7
THC (ng/mL) in Plasma
Smoking a Single Cigarette
3.55 % THC
6
5
4
3
2
1
0
0
2
4
6
8
Time (hrs)
10
12
14
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.
Smoking a Single Cigarette
3.55 % THC
THC (ng/mL) - Plasma
300
250
200
THC
THCCOOH
150
11-OH-THC
100
50
0
0
2
4
Time (hrs)
6
8
THC (ng/mL) - Plasma
Smoking a Single Cigarette
3.55 % THC
80
70
60
50
40
30
20
10
0
THC
THCCOOH
11-OH-THC
0
1
2
Time (hrs)
3
4
THC (ng/mL) in Plasma
Smoking a Single Cigarette 3.55% THC
Casual and Chronic Smoker
14
12
10
8
Casual
6
Chronic
4
2
0
0
5
10
Time (hrs)
15
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?
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
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
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.
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 = 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 - 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
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
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)
Testimony Last Week



THC
THCCOOH
Issues







8.7 ng/mL
19 ng/mL
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?
Opiates and Opioids

Major issues

Dose can vary tremendously from person to person
•
•

Tolerance develops for almost all opiates
•

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 can be lost or greatly diminished with only one
day of abstinence
Do pharmacokinetic calculations allow toxicologist
to estimate expected concentration after dosing?
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.
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?


People have a right to drive with
prescribed drugs.
They do not have a right to drive while
impaired by prescribed drugs.
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
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