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For The Defense  ■  April 2016  ■  77
T R U C K I N G L A W
■  Annette B. Santamaria, PhD, MPH, DABT, is a board-certified toxicologist with Rimkus Consulting Group
in Houston, a corporate member of DRI. She has over 25 years of multidisciplinary experience critically eval-
uating a broad range of toxicological, epidemiological, and clinical studies, conducting exposure and human
health risk assessments, and communicating results to clients and governmental agencies. Carla Kinslow,
PhD, a toxicologist with Rimkus, has over 25 years of biomedical, regulatory, and environmental experience.
She has expertise in inhalation toxicology, toxicogenomics, toxicological risk assessment, ambient air moni-
tor placement, human health impacts analysis from emission events, monitoring data, modeling data related
to ambient and indoor air quality, and stakeholder communication.
Marijuana and Driving
Can a Blood or Urine
Test Determine
Impairment?
Marijuana is mentioned in historical texts
dating back at least 5,000 years, and its
recreational and medicinal uses have been
well documented for centuries (Bostwick
2012;Littlebury,1737).IntheUnitedStates,
marijuana was officially listed as an ille-
gal substance in 1937, and its lawfulness
has been debated ever since. The recre-
ational use of marijuana in the United
States emerged most notably in the 1960s
as part of a counter-­culture movement. At
that time, its use evoked a negative conno-
tation and was associated closely with the
use of other illicit drugs such as cocaine
and heroin. Over the years, the public and
scientific view of marijuana use has soft-
ened as researchers have found beneficial
uses of the drug for medicinal purposes. In
2013, the U.S. federal government allowed
legalization and oversight at the state level
(NCSL 2016). As of early 2016, 25 states had
legalized medical marijuana, and 17 others
had passed limited access marijuana prod-
uct (low THC/high CBD-­cannabidiol) laws
(NCSL 2016). However, one may argue that
complete legalization of this very complex
and understudied drug is a bit premature.
One point to consider is that many state
governments have set legal thresholds for
marijuana exposure that are intended to
identify drivers who are impaired. How-
ever, there is no accepted, scientifically-­
based biological threshold for impairment
from marijuana.
The following white paper is designed
to help the reader understand the current
state of the science with respect to how
marijuana affects the body, how to test for
By Annette B. Santamaria
and Carla J. Kinslow
The recent trend to
legalize marijuana
use by various states
makes understanding
marijuana science, tests,
and potential effects
important to protecting
trucking operating
companies and the public.
The illegality of cannabis is outrageous, an impediment
to full utilization of a drug which helps produce the seren-
ity and insight, sensitivity and fellowship so desperately
needed in this increasingly mad and dangerous world.
—Carl Sagan, 1969
© 2016 DRI. All rights reserved.
78  ■  For The Defense  ■  April 2016
T R U C K I N G L A W
its effects, and how toxicology can be used
to provide a better understanding of the
effects of marijuana impairment on activi-
ties such as driving.
What Is Marijuana?
Many marijuana advocates boast that it is a
“natural” product that has been used safely
for millennia; however, today’s marijuana
is not the same as that of the Greeks (Lit-
tlebury 1737; Wargo 2013). Over the years,
marijuana aficionados, kitchen chem-
ists, and backyard cultivators have devel-
oped ways to elevate their “high” through
breeding, extraction, and further concen-
trating the psychoactive components of
marijuana. This has resulted in marijuana
that is as much as 22 times more potent
than that of the 1960s (Greydanus et al.
2013; Volkow et al. 2014). Resinous secre-
tions from the plant can be collected, dried,
compressed, and smoked as hashish. Hash-
ish oil is extracted using a solvent and
can also be smoked, eaten, or vaporized
(NHTSA 2004). Each of these techniques
effectively concentrates the main psycho-
active compound, delta-­9-­tetrahydrocan-
nabinol (THC), thus creating a more potent
“high”. This process results in the unin-
tended concentration of many other chem-
icals as well, including pesticides (Raber et
al. 2015).
THC is one of many naturally occur-
ring cannabinoids in marijuana and is
the most significant and potent psycho-
active cannabinoid in the plant. The aver-
age THC concentration in marijuana can
range between 1–22 percent, with concen-
trations in hashish ranging between 5–15
percent and concentrations in hashish oil
raging between 3–20 percent (Greydanus et
al. 2013; NHTSA 2004). Marijuana canna-
binoids have also used for medicinal pur-
poses. For example, Dronabinol (Marinol)
is a synthetic THC that has several clinical
uses, such as an appetite stimulant and an
antiemetic to treat or prevent nausea and
vomiting caused by cancer medications or
to increase the appetite in AIDS patients.
Acute Health Effects of Marijuana
Once inhaled, THC blood concentration
peaks between 3–10 minutes, quickly
followed by psychological effects within
5–30 minutes (Huestis 2007; Neavyn et
al. 2014). Marijuana induces acute effects
in multiple organ systems, including car-
diovascular, respiratory, immune, gas-
trointestinal, and neurological (Sachs et
al. 2015). Acute, dose-­dependent cardio-
vascular effects of marijuana exposure
includes tachycardia, increased car-
diac labor, systemic vasodilation, and
increased blood pressure (Sachs et al.
2015). The acute respiratory effects include
increased airway resistance, inflamma-
tion of large airways, and damaged lung
tissue (Sachs et al. 2015). It is clear that
marijuana affects cognitive behavior, and
there is strong evidence that short-term
cannabis use can affect a user’s ability to
have free recall, acquisition of informa-
tion, working memory, and procedural
memory (Sachs et al. 2015). Other cogni-
tive abilities that are impaired by short-
term use include attention, impulsivity,
inhibition, sensory perception, and exec-
utive function (Sachs et al. 2015). Addi-
tional acute effects include increased total
sleep at the cost of poor sleep quality,
impairments of gross motor tasks, and
decrements in decision making (Sachs et
al. 2015). Notably, all of these abilities that
marijuana affects are essential to navigat-
ing a vehicle properly (Sachs et al. 2015).
The many types of cognitive impair-
ments that are effected by short-term can-
nabis use are transient and diminish over
time upon cessation of marijuana use
(Sachs et al. 2015). Yet, there are some
studies that indicate functional alterations
in the brain can be found in adolescents
shortlyafterusingthisdrug,suggestingthe
younger brain may be uniquely susceptible
to long-term damage even after short-term
exposure (Sachs, 2015).
Chronic Health Effects of Marijuana
There is some evidence of persistent neu-
rophysiological impairments after chronic
use of marijuana; however, the risk of
developing these impairments is related
to the age of initial use and the frequency
and duration of use (Sachs et al. 2015).
Essentially serious deficits of IQ, visual
attention, verbal fluency, inhibition, short-
term recall, impulsivity, and executive
functions have been associated with early
(young adult) and prolonged use of mari-
juana (Sachs et al. 2015). Importantly, with
early and chronic use, these conditions are
not transient, and cognitive deficits may
remain after cessation (Sachs et al. 2015).
Chronic use since adolescence is also asso-
ciated with structural abnormalities in
the brain of the adult and has been shown
to cause a reduction in the size of specific
regions of the brain, including the parahip-
pocampal, hippocampal, and thalamic vol-
umes (Sachs et al. 2015).
Immune disorders associated with
marijuana use are complex and not fully
understood and there is evidence that mar-
ijuana is immunosuppressive and has been
shown to have anti-­inflammatory prop-
erties (Sachs et al. 2015). Based on lim-
ited information, researchers speculate
that naturally-­occurring cannabinoids
(endocannabinoids) generally enhance the
immune response, whereas exogenous can-
nabinoids, such as those in marijuana,
play a role in immunosuppression (Sachs
et al. 2015).
Pharmacokinetics of Marijuana
The very complicated pharmacokinet-
ics (absorption, distribution, metabolism,
excretion, ADME) of marijuana (THC and
other metabolites) has been studied for
decades. The early studies focused on the
effects of the drug on behavior and less on
the toxicity or complex pharmacological
properties of the drug. The recent interest
in legalizing the drug has driven a four-fold
increase in scientific studies over the past
15 years, and these studies have shown that
There is some evidence of
persistent neurophysiological
impairments after chronic
use of marijuana; however,
the risk of developing
these impairments is
related to the age of initial
use and the frequency
and duration of use.
For The Defense  ■  April 2016  ■  79
marijuana is a complex mixture of chem-
icals that have both beneficial and detri-
mental health effects. Other than THC,
there are more than 100 different cannabi-
noids in marijuana, many of which can be
metabolized to other reactive compounds.
While scientific studies on the effects of
marijuana have increased, the full effects
are still unknown. One complicating fac-
tor in understanding its metabolism is that
there are 100 currently known metabolites
of THC (Huestis 2007).
Once ingested or inhaled, THC is
quickly absorbed into the blood stream
and systemically distributed throughout
the body. The general order of organ dep-
osition over time for THC is first in the
blood-brain-high profusion tissues (heart,
lung, liver), secondly in the low perfusion
tissues (adrenal glands, skin), and then it is
ultimately stored in fat (Kreutz and Axel-
rod 1973). With prolonged use, THC will
concentrate in fat, suggesting that THC
forms stable fatty acid conjugates. Fat dep-
osition is an important factor in the inter-
pretation of testing results, especially for
chronic marijuana users. Over time and
during abstinence, THC redistributes from
the fat tissue to the blood stream, and then
systemically. THC is primarily metabo-
lized in the liver to two primary metab-
olites, 11-­hydroxytetrahydrocannabinol
(11-OH-THC) and 11-nor-9-­carboxy-
tetrahydrocannabinol(THCCOOH),which
are eliminated in the urine (Huestis 2007).
THC COOH in the urine is used as an indi-
rect indicator for THC exposure or past
marijuana use. Chronic users may have
detectable THC COOH in their urine for
weeks or months after cessation due to
the slow release of THC from fat tissues,
which is then metabolized to THC COOH.
However, for acute or occasional users,
detectable THC COOH in the urine may be
present for less than 24 hours (Battistella et
al. 2013; Huestis et al. 2006). It is suggested
that prolonged retention of THC in heavy
cannabis users is responsible for the pro-
longed detection of THC COOH in urine,
cannabis-­related flashbacks, and cognitive
deficits (Huestis 2007).
Incontrasttoalcoholimpairmenteffects,
which are driven by one primary compo-
nent (ethanol), marijuana is a mixture of
different components that contribute to
multiple (positive and negative) effects in
individuals. Smoking or eating marijuana
has been shown to induce psychoactive,
pain-­killing, appetite stimulation, anti-­
nausea, and many other effects, many of
which are currently under study. It is well
known that marijuana has diverse and
individual psychoactive effects in humans;
however, it is the individual-­specific nature
of these effects that makes it very difficult
to determine the dose-­response associated
with the use of marijuana and impaired
driving for the general public.
Factors Affecting Determining Dose-
Response of Marijuana Impairment
Variability in dose, exposure duration, and
metabolism can dramatically affect how a
drugsuch asmarijuanawouldaffect behav-
ior. Alcohol is an example of a more simple
and predicable dose-response relationship
involving one substance (ethanol), and
increases in alcohol consumption directly
correlates to increased driving impair-
ment. Marijuana is a mixture of about
100 different cannabinoids, all with differ-
ent efficacies (Huestis 2007). When con-
sidering how marijuana as a drug would
affect behavior, all of these compounds
may play a role, so one cannot assume
that effects are accounted for by a simple
dose-­relationship model. Alcohol levels,
which have linear pharmacokinetics, are
easier to back-­calculate to the time of an
accident, and they are consistently linked
with increased culpability in automobile
accidents (Sewell et al. 2009). In addition,
alcohol in the blood, which moves easily
throughout the body with little difference
in concentration between bodily compart-
ments (e.g., blood, fat), can be approx-
imated with a good degree of accuracy
through measuring blood or breath levels
(Sewell et al. 2009). However, the same is
not true of THC, which is highly lipophilic
and concentrates preferentially in fat tis-
sue. Consequently, experimental studies
have shown that functional impairment of
marijuana, which reaches a maximum an
hour after smoking, lags behind THC blood
level, which peaks within minutes and then
decreases rapidly thereafter (Sewell et al.
2009). Therefore, it is much harder to gen-
erate blood level versus impairment curves
for marijuana than it is for alcohol.
Exposure to inhaled marijuana is mea-
sured by how deeply someone breathes in
and how long he or she holds their breath
before exhaling. These factors vary greatly
amongst individuals and are reported to
contribute to the inconsistencies in dose-
behavior responses found within and
between studies (Huestis 2007). The pri-
mary routes of exposure are smoking
(inhalation) or eating (ingestion) and the
bioavailabilityofmarijuanavariesamongst
individuals by 10–35 percent when smoked
and5–20percent when ingested (Neavyn et
al. 2014). Furthermore, as discussed above,
cannabinoid concentrations in marijuana
can vary by as much as 22-fold between
the different types, and no two “joints”
contain the same quantity of marijuana
(NHTSA 2004). Therefore, the exposure
concentration of THC (“dose”) from one
joint to the next (or other forms of admin-
istration) is not uniform and is very diffi-
cult to ascertain.
The metabolism of marijuana can vary
based on route of exposure, chronic or
acute use, and individual biochemistry
(Huestis 2007). Smoking is an efficient
method to allow THC to quickly enter the
blood stream through the lungs, but con-
trolled clinical studies have shown that
the maximum THC concentration in the
blood can vary by 5-fold within the first
15 minutes of inhalation (Schwope et al.
2011). Once in the blood stream, it can
quickly move to the brain to affect behav-
ior (Huestis 2007). Smoking is not rec-
ommended for medicinal uses due to the
harmful effects of smoking, so ingestion
is an alternative route recommended for
medicinal uses (Huestis 2007). However,
if a quick “high” is the goal, ingestion is
not as efficient because absorption of THC
Variability in dose,
exposure duration,
and metabolism can
dramatically affect how a
drug such as marijuana
would affect behavior.
80  ■  For The Defense  ■  April 2016
T R U C K I N G L A W
is slower when ingested and results in a
more delayed peak in THC concentrations
(Huestis 2007).
Recentstudieshaveshownthatcannabis
dependence, cannabis craving, and with-
drawal symptoms due to cannabis absti-
nence can be associated with idiosyncratic
genetic differences, including genetic poly-
morphisms. Furthermore, cannabinoid
metabolism can be inhibited by the reduc-
tion of active drug transporters in the liver
(Greydanus et al. 2013).
Marijuana Impairment and Driving
“I have mentioned that in the cannabis
experience there is a part of your mind
that remains a dispassionate observer,
who is able to take you down in a hurry
if need be. I have on a few occasions
been forced to drive in heavy traffic
when high. I’ve negotiated it with no
difficulty at all, though I did have some
thoughts about the marvelous cherry-
red color of traffic lights.”
Carl Sagan, 1969.
There is a global understanding that
cannabis confers an array of diverse and
many times unpredictable effects on the
brain. Marijuana produces its psychoactive
effects by targeting innate receptors of the
brain, including the basal ganglia, cerebel-
lum, hippocampus, neocortex, and hypo-
thalamus (Sachs et al. 2015). Studies have
shown that marijuana has profound effects
on the brain, specifically changing signal-
ing to nerve cells through release of various
brain-­specific messengers, such as dopa-
mine (Neavyn et al. 2014). Clinical stud-
ies have shown that blood flow amongst
different areas of the brain changes dur-
ing marijuana smoking and these find-
ings indicate that it affects many brain
processes that are important for driving,
including decreases in perceptual motor
control, motor inhibition, and cognition
(Neavyn et al. 2014; Battistella et al. 2013).
Interestingly, marijuana-­smoking drivers
try to compensate for their deficiency by
slowing down in traffic, which is in con-
trast to alcohol impaired drivers who are
more reckless and may speed (Battistella
et al. 2013; Neavyn et al. 2014). Taken
together, the majority of psychomotor tests
indicate that marijuana use affects the
skills needed to drive a vehicle; however,
the crash test data does not support this
conclusion (Battistella et al. 2013; Neavyn
et al. 2014; NHTSA 2015).
The National Transportation Safety
Board (NTSB) states that impairment
from alcohol or drugs accounts for one-
third of all road fatalities (NTSB 2013).
One National Highway Transportation
Safety Administration (NHTSA) “Crash
Risk” Study reported 10 percent of 3,000
crash-involved drivers tested positive for
illegal drug use (NTHSA 2015). Statistics
for the general public appear to be differ-
ent from those for the trucking commu-
nity. Illegal drug use can play a significant
role in trucking accidents, however, the
results from the Large Truck Crash Causa-
tion Study performed by the Transporta-
tion Research Board indicates that illegal
drug use accounted for only 2.3 percent
of accidents (TRB 2010). Importantly, ille-
gal drug use was ranked 24th of 25 factors
that contributed to truck crashes and mar-
ijuana use is only a portion of this value.
An analysis by the Federal Motor Car-
rier Safety Administration showed that
drugs were detected in 13.8 percent of
fatal accidents involving truck drivers in
2013 (FMCSA 2015). With respect to crash-
risk data, it is important to focus on the
correct statistics to get the most accurate
picture of the potential driving risks asso-
ciated with marijuana use in automobile or
truck drivers.
According to a report from the Depart-
ment of Health and Human Services of
Oregon, in the United States, the num-
ber of drivers using marijuana involved
in fatal collisions significantly increased
from 29 percent to 37 percent from 1993
to 2010 (Repp and Raich 2014). According
to the report, the percent of “marijuana-­
drugged” drivers involved in fatal crashes
increased 49 percent pre-­legalization to
post-­legalization of medical marijuana
in Oregon (Repp and Raich 2014). Crash
research demonstrates that marijuana is
usually used in conjunction with alco-
hol ingestion (Repp and Raich 2014). With
marijuana use alone, the odds of a fatal
motor vehicle crash increase approximately
two times and with alcohol ingestion alone
the odds of a fatal crash increase approx-
imately 14 times (Repp and Raich 2014).
According to the Oregon report, driving
under the influence of both alcohol and
drugs increases the odds of a fatal motor
vehicle crash over 23 times relative to those
drivers without drugs and alcohol in their
system (Repp and Raich 2014).
Testing requirements and testing pro-
cedures for the trucking industry are reg-
ulated by the United States Department
of Transportation (USDOT) and may be
found in the Code of Federal Regulations
under the “Procedures for Transporta-
tion Workplace Drug and Alcohol Test-
ing Programs” (USDOT 2015). Under the
“Cutoff Concentrations for Drug-­Testing”
rule, employees are initially tested for THC
COOH by urinalysis, and they must be
below the cutoff concentration of 50 nano-
grams per milliliter (ng/mL) to be con-
sidered negative. If a result is at or above
the USDOT cutoff concentration, a con-
firmation test must be conducted, and a
positive test is considered above the con-
firmatory cutoff of 15 ng/mL THC COOH
(USDOT 2015).
Crash Test Studies of
Marijuana Impairment
There have been numerous studies to eval-
uate the potential for marijuana-­induced
car accidents due to driver impairment
(Hels et al. 2011; NHTSA 1999; NHTSA
2015; Ramaekers et al. 2004). Each of
these studies has many limitations, in-
cluding the lack of control groups and
documented pre-­exposure. Furthermore,
the body of literature is not consistent
with respect to the attribution of mar-
ijuana to driving impairment (NHTSA
2015). Some studies have concluded
that marijuana use alone has no effect
on crash risk, while others have esti-
mated an increase in crashes (NHTSA
There is a global
understanding that
cannabis confers an
array of diverse and
many times unpredictable
effects on the brain.
For The Defense  ■  April 2016  ■  81
2015). A recent population-­based study
known as Driving Under the Influence of
Drugs, Alcohol and Medicines (DRUID),
was the largest study of this type and
included nine European Union (EU) coun-
tries (Hels et al. 2011). The study con-
cluded that there is extreme variability for
risk of vehicle crashes among those test-
ing positive for marijuana, ranging from
0.29 times (reduced crash involvement)
to 25.38 times (increased crash involve-
ment) (Hels et al. 2011). A more recent
study by NHTSA (2015) evaluated 3,000
drivers involved in crashes and 6,000 con-
trol drivers not involved in crashes in Vir-
ginia Beach, Virginia. The results showed
that both control (6.1 percent) and crash
(7.6 percent) drivers tested positive for
THC. This study found that marijuana
use was statically associated with crashes;
however, the population of crash subjects
has a disproportionate number of young
males, which were already at a high risk
for car crashes.
Taken together, there is a lack of scien-
tific evidence that definitively confirms an
increased crash risk with testing positive
for THC.
Clinical Testing for Marijuana
Obtaining a representative cannabinoid
concentration (THC or THC COOH) from
a person is essential to understanding the
effects of smoking or ingesting marijuana
on driving behavior. For marijuana, four
types of biological samples can be col-
lected and examined for cannabinoid con-
centration; blood, urine, saliva, or hair.
There are advantages and disadvantages
to each.
Blood samples represent the most accu-
rate account of THC concentration, and
THC correlates well with psychomotor
deficiencies (Huestis 2007), especially after
acute exposure. THC is rapidly metabo-
lizedwithin30minutesofinhalationexpo-
sure and blood concentrations can drop to
below 5 micrograms per liter (µg/L) within
3 hours of exposure for non-­chronic users
(Battistella et al. 2013). Thus, to corre-
late behavior such as impaired driving to
THC blood concentrations, samples should
be taken and analyzed as soon as possi-
ble. Additionally, taking blood samples is
considerably more invasive and requires a
skilled technician. These factors pose sig-
nificant challenges to using blood as the
testing media to indicate driving impair-
ment. Blood samples may be beneficial in
legal cases because generally an accurate
concentration is required to determine an
exceedance of a legal threshold. THC con-
centration in saliva correlates well with
blood concentrations, and saliva testing is
less invasive, provides rapid results, and is
currently being used for road-side testing
(Lee and Huestis 2014). However, the con-
centration of THC in saliva that directly
corresponds to deficiencies in psycho-
active behavior has not been fully eluci-
dated, and there is considerable variability
among testing populations. Urine test-
ing offers an opportunity to test only for
the presence of THC COOH. This meth-
odology is even less invasive, but it pro-
vides little information regarding recent
marijuana use because THC COOH can be
detected in the urine for weeks to months
after drug use (Huestis 2007). Hair test-
ing is the least invasive and has been used
extensively, especially for marijuana-­
related cases involving employment and
child protection (Moosmann 2015; Pichini
2014). However, interpretation of hair-test
results for THC, THC COOH, or THCA-
A (Δ 9-­tetrahydrocannabinolic acid A,
the non-­psychoactive precursor of THC),
is limited to past use or passive second-
hand exposure. Studies have shown that
these three cannabinoids can be detected
in hair of non-­consuming individuals due
to transfer through the cannabis consumer
via touch, sebum/sweat, or smoke (Moos-
mann 2015; Pichini 2014). It is generally
accepted that hair is not an appropriate
medium to illustrate impairment or recent
use (Moosmann 2015).
There are a few studies that have shown
that storage conditions and containers
used for the biological sample can affect
THC testing results (McCurdy et al. 1989;
Schwope et al. 2011; Stout et al. 2000).
Collection of whole blood in plastic con-
tainers and stored at room tempera-
ture (20–25°C), followed by being frozen
for four weeks can result in a 0–40 per-
cent decrease of THC in the samples. No
change in THC concentration was found
in those samples collected in glass vials
(McCurdy et al. 1989). Another study of
THC COOH in urine collected in plas-
tic containers reported a 14–17 percent
decrease in THC COOH when samples
were stored at 4°C. Samples stored at 25°C,
a higher temperature, indicate 5 percent
decrease in THC COOH levels (Stout et
al. 2000). This presents yet another layer
of uncertainty with interpreting testing
results relative to impairment at the time
that the biological sample was collected.
Mathematical Models to Predict
Past Exposure and Impairment
Clinical data (e.g., blood, breath) taken
after an accident are commonly used to
determine blood alcohol content and level
of impairment before, or at the time of an
accident. As previously discussed, the way
that the body responds to and metabolizes
alcohol easily permits the use of predic-
tive models. Those models provide sci-
entifically valid and practical estimates
for interpreting the level of impairment
due to alcohol at the time of an accident.
Unfortunately, cannabinoid metabolism
is considerably more complicated. This is
due to possible psychoactive effects from
multiple cannabinoids that can contrib-
ute to impairment. In addition, THC can
be stored in fat tissues and later released in
chronic marijuana users; it is metabolized
by enzymes that are known to have a vary-
ing rate of activity, and the pharmacoki-
netics and pharmacodynamics depend on
the individual (Huestis 2007). Early stud-
ies in the development of pharmacokinetic
models for marijuana were promising and
may be considered in some cases (Huestis
et al. 1992). However, the application and
interpretation of these models should be
performed with caution, and limitations
should be clearly stated.
There have been
numerous studies to
evaluate the potential
for marijuana-­induced
car accidents due to
driver impairment.
82  ■  For The Defense  ■  April 2016
T R U C K I N G L A W
Furthermore, it is hard for a marijuana
smoker to predict his or her own psy-
chological responses to different types of
marijuana. There is no standard concen-
tration labeling for a joint or a marijuana-­
containing food product as there is for
alcohol products, such as a bottle of beer,
which would have labeling indicating the
beer’s alcohol concentration. Thus, even if
someone self-reports marijuana use, the
dose would be unknown and can be very
difficult to determine.
There are several important weaknesses
in the body of literature regarding the
metabolism of cannabinoids and how can-
nabinoids affect psychomotor skills, as well
as driving skills. The most striking limita-
tion is an almost global lack of pre-­study
testing for THC or THC COOH to deter-
mine baseline levels, which may be pres-
ent in the case of chronic users, especially
in the early studies. In addition, most stud-
ies rely on questionnaires to self-report
prior cannabis use, which may bias the
study results. Without understanding the
pre-study cannabinoid concentrations, the
attribution of the test substance versus
that from previous exposures to the test-
ing endpoint (e.g. blood concentrations,
urine concentrations, psychomotor test-
ing, among others) would be in question
(Sachs et al. 2015). This limits the applica-
tion of these studies for determining the
contribution of the drug to a level of mea-
sured impairment.
Global variation in smoking behavior is
also a significant factor to consider when
applying study data to forensic analysis for
marijuana. In one small study, the authors
attribute reported cannabinoid concentra-
tions in clinical samples to differences in
smoking behaviors, including side-stream
inhalation, smoking retention, and depth
of inhalation (Schwope et al. 2011). Another
problem with many of these studies is the
lack of appropriate control groups (Neavyn
et al. 2014; Sachs et al. 2015).
How Toxicology Can Help Evaluate
Marijuana Impairment
As discussed above, testing positive for
marijuana does not automatically indi-
cate impairment or an increase in crash
risk. A study by the NHTSA indicated that
there appears to be virtually no difference
in the percentage of crash-involved driv-
ers testing positive for legal drugs (5.6 per-
cent) and control drivers testing positive
for legal drugs (5.5 percent). However, for
illegal drugs, a statistically significantly
10.4 percent of the crash-involved drivers
tested positive compared to 8.8 percent of
control drivers that tested positive for ille-
gal drugs (NHTSA 2015).
There is scientific consensus that the
combination of alcohol and marijuana re-
sults in a synergistic effect on the reckless
behavior of the intoxicated driver, result-
ing in a several-fold increase in crash risk
compared with alcohol or marijuana alone
(Battistella et al. 2013). It is suggested that
when starting with a blood alcohol con-
centration of 0.07 percent (g/dL), the addi-
tion of either low or moderate THC results
in decrements in driving performance that
are similar to those with blood alcohol con-
centration (BAC) concentrations between
0.09 percent and 0.14 percent, respectively
(NHTSA 1999).
Toxicology can be used to help under-
stand how or to what extent the clini-
cal data indicate impairment, or if other
contributing factors could be involved.
NHTSAstudiesindicatethatmarijuanause
is frequently associated with other drugs
or alcohol, including prescription drugs
(NHTSA 1999; NHTSA 2015). A toxicolo-
gist can examine the blood or urine sam-
ple for the presence of other substances at
levels that can be attributed to impairment
by legal or illegal drugs. A toxicologist can
also help with understanding the limita-
tions in the use of mathematical models
to predict past exposure, as well as the sig-
nificant issues regarding identifying the
marijuana dose-responses associated with
various levels and forms of impairment.
Conclusion
Attributing a level of impairment to a level
of marijuana use is quite complicated, pri-
marily because there is a lack of scientific
consensus about the dose-response for
the amount of inhaled or ingested mari-
juana that is associated with various lev-
els of impairment. A dose-response is
necessary to mathematically identify a
threshold for impairment during an activ-
ity such as driving by a marijuana user.
In addition, the behavioral and cognitive
responses from the use of marijuana vary
dramatically among individuals. How-
ever, blood, urine, and saliva are being
used to assess marijuana use and impair-
ment in many states in the United States,
and there may be some cases of false pos-
itives with respect to whether someone is
actually impaired. In addition, an evalua-
tion of a positive test of low levels of TCH
may incorrectly conclude that someone
is not impaired. Toxicologists can eval-
uate clinical data obtained from a driver
involved in an accident and evaluate how
it can be associated or not associated with
impairment. In addition, there are many
scientific studies underway to evaluate the
effects of marijuana, particularly in light of
legalization for medicinal or recreational
use in so many states, so this is a rapidly
developing, evolving, and challenging area
of science.
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Santamaria and Kinslow 2016

  • 1. For The Defense  ■  April 2016  ■  77 T R U C K I N G L A W ■  Annette B. Santamaria, PhD, MPH, DABT, is a board-certified toxicologist with Rimkus Consulting Group in Houston, a corporate member of DRI. She has over 25 years of multidisciplinary experience critically eval- uating a broad range of toxicological, epidemiological, and clinical studies, conducting exposure and human health risk assessments, and communicating results to clients and governmental agencies. Carla Kinslow, PhD, a toxicologist with Rimkus, has over 25 years of biomedical, regulatory, and environmental experience. She has expertise in inhalation toxicology, toxicogenomics, toxicological risk assessment, ambient air moni- tor placement, human health impacts analysis from emission events, monitoring data, modeling data related to ambient and indoor air quality, and stakeholder communication. Marijuana and Driving Can a Blood or Urine Test Determine Impairment? Marijuana is mentioned in historical texts dating back at least 5,000 years, and its recreational and medicinal uses have been well documented for centuries (Bostwick 2012;Littlebury,1737).IntheUnitedStates, marijuana was officially listed as an ille- gal substance in 1937, and its lawfulness has been debated ever since. The recre- ational use of marijuana in the United States emerged most notably in the 1960s as part of a counter-­culture movement. At that time, its use evoked a negative conno- tation and was associated closely with the use of other illicit drugs such as cocaine and heroin. Over the years, the public and scientific view of marijuana use has soft- ened as researchers have found beneficial uses of the drug for medicinal purposes. In 2013, the U.S. federal government allowed legalization and oversight at the state level (NCSL 2016). As of early 2016, 25 states had legalized medical marijuana, and 17 others had passed limited access marijuana prod- uct (low THC/high CBD-­cannabidiol) laws (NCSL 2016). However, one may argue that complete legalization of this very complex and understudied drug is a bit premature. One point to consider is that many state governments have set legal thresholds for marijuana exposure that are intended to identify drivers who are impaired. How- ever, there is no accepted, scientifically-­ based biological threshold for impairment from marijuana. The following white paper is designed to help the reader understand the current state of the science with respect to how marijuana affects the body, how to test for By Annette B. Santamaria and Carla J. Kinslow The recent trend to legalize marijuana use by various states makes understanding marijuana science, tests, and potential effects important to protecting trucking operating companies and the public. The illegality of cannabis is outrageous, an impediment to full utilization of a drug which helps produce the seren- ity and insight, sensitivity and fellowship so desperately needed in this increasingly mad and dangerous world. —Carl Sagan, 1969 © 2016 DRI. All rights reserved.
  • 2. 78  ■  For The Defense  ■  April 2016 T R U C K I N G L A W its effects, and how toxicology can be used to provide a better understanding of the effects of marijuana impairment on activi- ties such as driving. What Is Marijuana? Many marijuana advocates boast that it is a “natural” product that has been used safely for millennia; however, today’s marijuana is not the same as that of the Greeks (Lit- tlebury 1737; Wargo 2013). Over the years, marijuana aficionados, kitchen chem- ists, and backyard cultivators have devel- oped ways to elevate their “high” through breeding, extraction, and further concen- trating the psychoactive components of marijuana. This has resulted in marijuana that is as much as 22 times more potent than that of the 1960s (Greydanus et al. 2013; Volkow et al. 2014). Resinous secre- tions from the plant can be collected, dried, compressed, and smoked as hashish. Hash- ish oil is extracted using a solvent and can also be smoked, eaten, or vaporized (NHTSA 2004). Each of these techniques effectively concentrates the main psycho- active compound, delta-­9-­tetrahydrocan- nabinol (THC), thus creating a more potent “high”. This process results in the unin- tended concentration of many other chem- icals as well, including pesticides (Raber et al. 2015). THC is one of many naturally occur- ring cannabinoids in marijuana and is the most significant and potent psycho- active cannabinoid in the plant. The aver- age THC concentration in marijuana can range between 1–22 percent, with concen- trations in hashish ranging between 5–15 percent and concentrations in hashish oil raging between 3–20 percent (Greydanus et al. 2013; NHTSA 2004). Marijuana canna- binoids have also used for medicinal pur- poses. For example, Dronabinol (Marinol) is a synthetic THC that has several clinical uses, such as an appetite stimulant and an antiemetic to treat or prevent nausea and vomiting caused by cancer medications or to increase the appetite in AIDS patients. Acute Health Effects of Marijuana Once inhaled, THC blood concentration peaks between 3–10 minutes, quickly followed by psychological effects within 5–30 minutes (Huestis 2007; Neavyn et al. 2014). Marijuana induces acute effects in multiple organ systems, including car- diovascular, respiratory, immune, gas- trointestinal, and neurological (Sachs et al. 2015). Acute, dose-­dependent cardio- vascular effects of marijuana exposure includes tachycardia, increased car- diac labor, systemic vasodilation, and increased blood pressure (Sachs et al. 2015). The acute respiratory effects include increased airway resistance, inflamma- tion of large airways, and damaged lung tissue (Sachs et al. 2015). It is clear that marijuana affects cognitive behavior, and there is strong evidence that short-term cannabis use can affect a user’s ability to have free recall, acquisition of informa- tion, working memory, and procedural memory (Sachs et al. 2015). Other cogni- tive abilities that are impaired by short- term use include attention, impulsivity, inhibition, sensory perception, and exec- utive function (Sachs et al. 2015). Addi- tional acute effects include increased total sleep at the cost of poor sleep quality, impairments of gross motor tasks, and decrements in decision making (Sachs et al. 2015). Notably, all of these abilities that marijuana affects are essential to navigat- ing a vehicle properly (Sachs et al. 2015). The many types of cognitive impair- ments that are effected by short-term can- nabis use are transient and diminish over time upon cessation of marijuana use (Sachs et al. 2015). Yet, there are some studies that indicate functional alterations in the brain can be found in adolescents shortlyafterusingthisdrug,suggestingthe younger brain may be uniquely susceptible to long-term damage even after short-term exposure (Sachs, 2015). Chronic Health Effects of Marijuana There is some evidence of persistent neu- rophysiological impairments after chronic use of marijuana; however, the risk of developing these impairments is related to the age of initial use and the frequency and duration of use (Sachs et al. 2015). Essentially serious deficits of IQ, visual attention, verbal fluency, inhibition, short- term recall, impulsivity, and executive functions have been associated with early (young adult) and prolonged use of mari- juana (Sachs et al. 2015). Importantly, with early and chronic use, these conditions are not transient, and cognitive deficits may remain after cessation (Sachs et al. 2015). Chronic use since adolescence is also asso- ciated with structural abnormalities in the brain of the adult and has been shown to cause a reduction in the size of specific regions of the brain, including the parahip- pocampal, hippocampal, and thalamic vol- umes (Sachs et al. 2015). Immune disorders associated with marijuana use are complex and not fully understood and there is evidence that mar- ijuana is immunosuppressive and has been shown to have anti-­inflammatory prop- erties (Sachs et al. 2015). Based on lim- ited information, researchers speculate that naturally-­occurring cannabinoids (endocannabinoids) generally enhance the immune response, whereas exogenous can- nabinoids, such as those in marijuana, play a role in immunosuppression (Sachs et al. 2015). Pharmacokinetics of Marijuana The very complicated pharmacokinet- ics (absorption, distribution, metabolism, excretion, ADME) of marijuana (THC and other metabolites) has been studied for decades. The early studies focused on the effects of the drug on behavior and less on the toxicity or complex pharmacological properties of the drug. The recent interest in legalizing the drug has driven a four-fold increase in scientific studies over the past 15 years, and these studies have shown that There is some evidence of persistent neurophysiological impairments after chronic use of marijuana; however, the risk of developing these impairments is related to the age of initial use and the frequency and duration of use.
  • 3. For The Defense  ■  April 2016  ■  79 marijuana is a complex mixture of chem- icals that have both beneficial and detri- mental health effects. Other than THC, there are more than 100 different cannabi- noids in marijuana, many of which can be metabolized to other reactive compounds. While scientific studies on the effects of marijuana have increased, the full effects are still unknown. One complicating fac- tor in understanding its metabolism is that there are 100 currently known metabolites of THC (Huestis 2007). Once ingested or inhaled, THC is quickly absorbed into the blood stream and systemically distributed throughout the body. The general order of organ dep- osition over time for THC is first in the blood-brain-high profusion tissues (heart, lung, liver), secondly in the low perfusion tissues (adrenal glands, skin), and then it is ultimately stored in fat (Kreutz and Axel- rod 1973). With prolonged use, THC will concentrate in fat, suggesting that THC forms stable fatty acid conjugates. Fat dep- osition is an important factor in the inter- pretation of testing results, especially for chronic marijuana users. Over time and during abstinence, THC redistributes from the fat tissue to the blood stream, and then systemically. THC is primarily metabo- lized in the liver to two primary metab- olites, 11-­hydroxytetrahydrocannabinol (11-OH-THC) and 11-nor-9-­carboxy- tetrahydrocannabinol(THCCOOH),which are eliminated in the urine (Huestis 2007). THC COOH in the urine is used as an indi- rect indicator for THC exposure or past marijuana use. Chronic users may have detectable THC COOH in their urine for weeks or months after cessation due to the slow release of THC from fat tissues, which is then metabolized to THC COOH. However, for acute or occasional users, detectable THC COOH in the urine may be present for less than 24 hours (Battistella et al. 2013; Huestis et al. 2006). It is suggested that prolonged retention of THC in heavy cannabis users is responsible for the pro- longed detection of THC COOH in urine, cannabis-­related flashbacks, and cognitive deficits (Huestis 2007). Incontrasttoalcoholimpairmenteffects, which are driven by one primary compo- nent (ethanol), marijuana is a mixture of different components that contribute to multiple (positive and negative) effects in individuals. Smoking or eating marijuana has been shown to induce psychoactive, pain-­killing, appetite stimulation, anti-­ nausea, and many other effects, many of which are currently under study. It is well known that marijuana has diverse and individual psychoactive effects in humans; however, it is the individual-­specific nature of these effects that makes it very difficult to determine the dose-­response associated with the use of marijuana and impaired driving for the general public. Factors Affecting Determining Dose- Response of Marijuana Impairment Variability in dose, exposure duration, and metabolism can dramatically affect how a drugsuch asmarijuanawouldaffect behav- ior. Alcohol is an example of a more simple and predicable dose-response relationship involving one substance (ethanol), and increases in alcohol consumption directly correlates to increased driving impair- ment. Marijuana is a mixture of about 100 different cannabinoids, all with differ- ent efficacies (Huestis 2007). When con- sidering how marijuana as a drug would affect behavior, all of these compounds may play a role, so one cannot assume that effects are accounted for by a simple dose-­relationship model. Alcohol levels, which have linear pharmacokinetics, are easier to back-­calculate to the time of an accident, and they are consistently linked with increased culpability in automobile accidents (Sewell et al. 2009). In addition, alcohol in the blood, which moves easily throughout the body with little difference in concentration between bodily compart- ments (e.g., blood, fat), can be approx- imated with a good degree of accuracy through measuring blood or breath levels (Sewell et al. 2009). However, the same is not true of THC, which is highly lipophilic and concentrates preferentially in fat tis- sue. Consequently, experimental studies have shown that functional impairment of marijuana, which reaches a maximum an hour after smoking, lags behind THC blood level, which peaks within minutes and then decreases rapidly thereafter (Sewell et al. 2009). Therefore, it is much harder to gen- erate blood level versus impairment curves for marijuana than it is for alcohol. Exposure to inhaled marijuana is mea- sured by how deeply someone breathes in and how long he or she holds their breath before exhaling. These factors vary greatly amongst individuals and are reported to contribute to the inconsistencies in dose- behavior responses found within and between studies (Huestis 2007). The pri- mary routes of exposure are smoking (inhalation) or eating (ingestion) and the bioavailabilityofmarijuanavariesamongst individuals by 10–35 percent when smoked and5–20percent when ingested (Neavyn et al. 2014). Furthermore, as discussed above, cannabinoid concentrations in marijuana can vary by as much as 22-fold between the different types, and no two “joints” contain the same quantity of marijuana (NHTSA 2004). Therefore, the exposure concentration of THC (“dose”) from one joint to the next (or other forms of admin- istration) is not uniform and is very diffi- cult to ascertain. The metabolism of marijuana can vary based on route of exposure, chronic or acute use, and individual biochemistry (Huestis 2007). Smoking is an efficient method to allow THC to quickly enter the blood stream through the lungs, but con- trolled clinical studies have shown that the maximum THC concentration in the blood can vary by 5-fold within the first 15 minutes of inhalation (Schwope et al. 2011). Once in the blood stream, it can quickly move to the brain to affect behav- ior (Huestis 2007). Smoking is not rec- ommended for medicinal uses due to the harmful effects of smoking, so ingestion is an alternative route recommended for medicinal uses (Huestis 2007). However, if a quick “high” is the goal, ingestion is not as efficient because absorption of THC Variability in dose, exposure duration, and metabolism can dramatically affect how a drug such as marijuana would affect behavior.
  • 4. 80  ■  For The Defense  ■  April 2016 T R U C K I N G L A W is slower when ingested and results in a more delayed peak in THC concentrations (Huestis 2007). Recentstudieshaveshownthatcannabis dependence, cannabis craving, and with- drawal symptoms due to cannabis absti- nence can be associated with idiosyncratic genetic differences, including genetic poly- morphisms. Furthermore, cannabinoid metabolism can be inhibited by the reduc- tion of active drug transporters in the liver (Greydanus et al. 2013). Marijuana Impairment and Driving “I have mentioned that in the cannabis experience there is a part of your mind that remains a dispassionate observer, who is able to take you down in a hurry if need be. I have on a few occasions been forced to drive in heavy traffic when high. I’ve negotiated it with no difficulty at all, though I did have some thoughts about the marvelous cherry- red color of traffic lights.” Carl Sagan, 1969. There is a global understanding that cannabis confers an array of diverse and many times unpredictable effects on the brain. Marijuana produces its psychoactive effects by targeting innate receptors of the brain, including the basal ganglia, cerebel- lum, hippocampus, neocortex, and hypo- thalamus (Sachs et al. 2015). Studies have shown that marijuana has profound effects on the brain, specifically changing signal- ing to nerve cells through release of various brain-­specific messengers, such as dopa- mine (Neavyn et al. 2014). Clinical stud- ies have shown that blood flow amongst different areas of the brain changes dur- ing marijuana smoking and these find- ings indicate that it affects many brain processes that are important for driving, including decreases in perceptual motor control, motor inhibition, and cognition (Neavyn et al. 2014; Battistella et al. 2013). Interestingly, marijuana-­smoking drivers try to compensate for their deficiency by slowing down in traffic, which is in con- trast to alcohol impaired drivers who are more reckless and may speed (Battistella et al. 2013; Neavyn et al. 2014). Taken together, the majority of psychomotor tests indicate that marijuana use affects the skills needed to drive a vehicle; however, the crash test data does not support this conclusion (Battistella et al. 2013; Neavyn et al. 2014; NHTSA 2015). The National Transportation Safety Board (NTSB) states that impairment from alcohol or drugs accounts for one- third of all road fatalities (NTSB 2013). One National Highway Transportation Safety Administration (NHTSA) “Crash Risk” Study reported 10 percent of 3,000 crash-involved drivers tested positive for illegal drug use (NTHSA 2015). Statistics for the general public appear to be differ- ent from those for the trucking commu- nity. Illegal drug use can play a significant role in trucking accidents, however, the results from the Large Truck Crash Causa- tion Study performed by the Transporta- tion Research Board indicates that illegal drug use accounted for only 2.3 percent of accidents (TRB 2010). Importantly, ille- gal drug use was ranked 24th of 25 factors that contributed to truck crashes and mar- ijuana use is only a portion of this value. An analysis by the Federal Motor Car- rier Safety Administration showed that drugs were detected in 13.8 percent of fatal accidents involving truck drivers in 2013 (FMCSA 2015). With respect to crash- risk data, it is important to focus on the correct statistics to get the most accurate picture of the potential driving risks asso- ciated with marijuana use in automobile or truck drivers. According to a report from the Depart- ment of Health and Human Services of Oregon, in the United States, the num- ber of drivers using marijuana involved in fatal collisions significantly increased from 29 percent to 37 percent from 1993 to 2010 (Repp and Raich 2014). According to the report, the percent of “marijuana-­ drugged” drivers involved in fatal crashes increased 49 percent pre-­legalization to post-­legalization of medical marijuana in Oregon (Repp and Raich 2014). Crash research demonstrates that marijuana is usually used in conjunction with alco- hol ingestion (Repp and Raich 2014). With marijuana use alone, the odds of a fatal motor vehicle crash increase approximately two times and with alcohol ingestion alone the odds of a fatal crash increase approx- imately 14 times (Repp and Raich 2014). According to the Oregon report, driving under the influence of both alcohol and drugs increases the odds of a fatal motor vehicle crash over 23 times relative to those drivers without drugs and alcohol in their system (Repp and Raich 2014). Testing requirements and testing pro- cedures for the trucking industry are reg- ulated by the United States Department of Transportation (USDOT) and may be found in the Code of Federal Regulations under the “Procedures for Transporta- tion Workplace Drug and Alcohol Test- ing Programs” (USDOT 2015). Under the “Cutoff Concentrations for Drug-­Testing” rule, employees are initially tested for THC COOH by urinalysis, and they must be below the cutoff concentration of 50 nano- grams per milliliter (ng/mL) to be con- sidered negative. If a result is at or above the USDOT cutoff concentration, a con- firmation test must be conducted, and a positive test is considered above the con- firmatory cutoff of 15 ng/mL THC COOH (USDOT 2015). Crash Test Studies of Marijuana Impairment There have been numerous studies to eval- uate the potential for marijuana-­induced car accidents due to driver impairment (Hels et al. 2011; NHTSA 1999; NHTSA 2015; Ramaekers et al. 2004). Each of these studies has many limitations, in- cluding the lack of control groups and documented pre-­exposure. Furthermore, the body of literature is not consistent with respect to the attribution of mar- ijuana to driving impairment (NHTSA 2015). Some studies have concluded that marijuana use alone has no effect on crash risk, while others have esti- mated an increase in crashes (NHTSA There is a global understanding that cannabis confers an array of diverse and many times unpredictable effects on the brain.
  • 5. For The Defense  ■  April 2016  ■  81 2015). A recent population-­based study known as Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID), was the largest study of this type and included nine European Union (EU) coun- tries (Hels et al. 2011). The study con- cluded that there is extreme variability for risk of vehicle crashes among those test- ing positive for marijuana, ranging from 0.29 times (reduced crash involvement) to 25.38 times (increased crash involve- ment) (Hels et al. 2011). A more recent study by NHTSA (2015) evaluated 3,000 drivers involved in crashes and 6,000 con- trol drivers not involved in crashes in Vir- ginia Beach, Virginia. The results showed that both control (6.1 percent) and crash (7.6 percent) drivers tested positive for THC. This study found that marijuana use was statically associated with crashes; however, the population of crash subjects has a disproportionate number of young males, which were already at a high risk for car crashes. Taken together, there is a lack of scien- tific evidence that definitively confirms an increased crash risk with testing positive for THC. Clinical Testing for Marijuana Obtaining a representative cannabinoid concentration (THC or THC COOH) from a person is essential to understanding the effects of smoking or ingesting marijuana on driving behavior. For marijuana, four types of biological samples can be col- lected and examined for cannabinoid con- centration; blood, urine, saliva, or hair. There are advantages and disadvantages to each. Blood samples represent the most accu- rate account of THC concentration, and THC correlates well with psychomotor deficiencies (Huestis 2007), especially after acute exposure. THC is rapidly metabo- lizedwithin30minutesofinhalationexpo- sure and blood concentrations can drop to below 5 micrograms per liter (µg/L) within 3 hours of exposure for non-­chronic users (Battistella et al. 2013). Thus, to corre- late behavior such as impaired driving to THC blood concentrations, samples should be taken and analyzed as soon as possi- ble. Additionally, taking blood samples is considerably more invasive and requires a skilled technician. These factors pose sig- nificant challenges to using blood as the testing media to indicate driving impair- ment. Blood samples may be beneficial in legal cases because generally an accurate concentration is required to determine an exceedance of a legal threshold. THC con- centration in saliva correlates well with blood concentrations, and saliva testing is less invasive, provides rapid results, and is currently being used for road-side testing (Lee and Huestis 2014). However, the con- centration of THC in saliva that directly corresponds to deficiencies in psycho- active behavior has not been fully eluci- dated, and there is considerable variability among testing populations. Urine test- ing offers an opportunity to test only for the presence of THC COOH. This meth- odology is even less invasive, but it pro- vides little information regarding recent marijuana use because THC COOH can be detected in the urine for weeks to months after drug use (Huestis 2007). Hair test- ing is the least invasive and has been used extensively, especially for marijuana-­ related cases involving employment and child protection (Moosmann 2015; Pichini 2014). However, interpretation of hair-test results for THC, THC COOH, or THCA- A (Δ 9-­tetrahydrocannabinolic acid A, the non-­psychoactive precursor of THC), is limited to past use or passive second- hand exposure. Studies have shown that these three cannabinoids can be detected in hair of non-­consuming individuals due to transfer through the cannabis consumer via touch, sebum/sweat, or smoke (Moos- mann 2015; Pichini 2014). It is generally accepted that hair is not an appropriate medium to illustrate impairment or recent use (Moosmann 2015). There are a few studies that have shown that storage conditions and containers used for the biological sample can affect THC testing results (McCurdy et al. 1989; Schwope et al. 2011; Stout et al. 2000). Collection of whole blood in plastic con- tainers and stored at room tempera- ture (20–25°C), followed by being frozen for four weeks can result in a 0–40 per- cent decrease of THC in the samples. No change in THC concentration was found in those samples collected in glass vials (McCurdy et al. 1989). Another study of THC COOH in urine collected in plas- tic containers reported a 14–17 percent decrease in THC COOH when samples were stored at 4°C. Samples stored at 25°C, a higher temperature, indicate 5 percent decrease in THC COOH levels (Stout et al. 2000). This presents yet another layer of uncertainty with interpreting testing results relative to impairment at the time that the biological sample was collected. Mathematical Models to Predict Past Exposure and Impairment Clinical data (e.g., blood, breath) taken after an accident are commonly used to determine blood alcohol content and level of impairment before, or at the time of an accident. As previously discussed, the way that the body responds to and metabolizes alcohol easily permits the use of predic- tive models. Those models provide sci- entifically valid and practical estimates for interpreting the level of impairment due to alcohol at the time of an accident. Unfortunately, cannabinoid metabolism is considerably more complicated. This is due to possible psychoactive effects from multiple cannabinoids that can contrib- ute to impairment. In addition, THC can be stored in fat tissues and later released in chronic marijuana users; it is metabolized by enzymes that are known to have a vary- ing rate of activity, and the pharmacoki- netics and pharmacodynamics depend on the individual (Huestis 2007). Early stud- ies in the development of pharmacokinetic models for marijuana were promising and may be considered in some cases (Huestis et al. 1992). However, the application and interpretation of these models should be performed with caution, and limitations should be clearly stated. There have been numerous studies to evaluate the potential for marijuana-­induced car accidents due to driver impairment.
  • 6. 82  ■  For The Defense  ■  April 2016 T R U C K I N G L A W Furthermore, it is hard for a marijuana smoker to predict his or her own psy- chological responses to different types of marijuana. There is no standard concen- tration labeling for a joint or a marijuana-­ containing food product as there is for alcohol products, such as a bottle of beer, which would have labeling indicating the beer’s alcohol concentration. Thus, even if someone self-reports marijuana use, the dose would be unknown and can be very difficult to determine. There are several important weaknesses in the body of literature regarding the metabolism of cannabinoids and how can- nabinoids affect psychomotor skills, as well as driving skills. The most striking limita- tion is an almost global lack of pre-­study testing for THC or THC COOH to deter- mine baseline levels, which may be pres- ent in the case of chronic users, especially in the early studies. In addition, most stud- ies rely on questionnaires to self-report prior cannabis use, which may bias the study results. Without understanding the pre-study cannabinoid concentrations, the attribution of the test substance versus that from previous exposures to the test- ing endpoint (e.g. blood concentrations, urine concentrations, psychomotor test- ing, among others) would be in question (Sachs et al. 2015). This limits the applica- tion of these studies for determining the contribution of the drug to a level of mea- sured impairment. Global variation in smoking behavior is also a significant factor to consider when applying study data to forensic analysis for marijuana. In one small study, the authors attribute reported cannabinoid concentra- tions in clinical samples to differences in smoking behaviors, including side-stream inhalation, smoking retention, and depth of inhalation (Schwope et al. 2011). Another problem with many of these studies is the lack of appropriate control groups (Neavyn et al. 2014; Sachs et al. 2015). How Toxicology Can Help Evaluate Marijuana Impairment As discussed above, testing positive for marijuana does not automatically indi- cate impairment or an increase in crash risk. A study by the NHTSA indicated that there appears to be virtually no difference in the percentage of crash-involved driv- ers testing positive for legal drugs (5.6 per- cent) and control drivers testing positive for legal drugs (5.5 percent). However, for illegal drugs, a statistically significantly 10.4 percent of the crash-involved drivers tested positive compared to 8.8 percent of control drivers that tested positive for ille- gal drugs (NHTSA 2015). There is scientific consensus that the combination of alcohol and marijuana re- sults in a synergistic effect on the reckless behavior of the intoxicated driver, result- ing in a several-fold increase in crash risk compared with alcohol or marijuana alone (Battistella et al. 2013). It is suggested that when starting with a blood alcohol con- centration of 0.07 percent (g/dL), the addi- tion of either low or moderate THC results in decrements in driving performance that are similar to those with blood alcohol con- centration (BAC) concentrations between 0.09 percent and 0.14 percent, respectively (NHTSA 1999). Toxicology can be used to help under- stand how or to what extent the clini- cal data indicate impairment, or if other contributing factors could be involved. NHTSAstudiesindicatethatmarijuanause is frequently associated with other drugs or alcohol, including prescription drugs (NHTSA 1999; NHTSA 2015). A toxicolo- gist can examine the blood or urine sam- ple for the presence of other substances at levels that can be attributed to impairment by legal or illegal drugs. A toxicologist can also help with understanding the limita- tions in the use of mathematical models to predict past exposure, as well as the sig- nificant issues regarding identifying the marijuana dose-responses associated with various levels and forms of impairment. Conclusion Attributing a level of impairment to a level of marijuana use is quite complicated, pri- marily because there is a lack of scientific consensus about the dose-response for the amount of inhaled or ingested mari- juana that is associated with various lev- els of impairment. A dose-response is necessary to mathematically identify a threshold for impairment during an activ- ity such as driving by a marijuana user. In addition, the behavioral and cognitive responses from the use of marijuana vary dramatically among individuals. How- ever, blood, urine, and saliva are being used to assess marijuana use and impair- ment in many states in the United States, and there may be some cases of false pos- itives with respect to whether someone is actually impaired. In addition, an evalua- tion of a positive test of low levels of TCH may incorrectly conclude that someone is not impaired. Toxicologists can eval- uate clinical data obtained from a driver involved in an accident and evaluate how it can be associated or not associated with impairment. In addition, there are many scientific studies underway to evaluate the effects of marijuana, particularly in light of legalization for medicinal or recreational use in so many states, so this is a rapidly developing, evolving, and challenging area of science. References • Battistella G, Fornari E, Thomas A, Mall JF, Chtioui H, Appenzeller M, Annoni JM, Favrat B, Maeder P, Giroud C. Weed or wheel! 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