Marijuana and the Cannabinoids

212 Huestis and Smith
trolled, randomized study (60). THC in hemp oil or Marinol was administered in three
divided daily doses at meals for 5 days. All urine specimens were collected over the
10-week study period and analyzed by several immunoassays and gas chromatography/mass
spectrometry (GC/MS). Maximum THC-COOH concentrations were 5.4–
38.2 ng/mL and 19.0–436 ng/mL for the two lower and two higher doses, respectively.
An important analytical study was published by Kemp et al. showing that significantly
higher concentrations of THC and 11-OH-THC in urine were found when
Escherichia coli β-glucuronidase was employed in the hydrolysis method compared
with either of the common hydrolysis methods using Helix pomatia glucuronidase or
base (61). Mean THC concentration in urine specimens from seven subjects collected
after each had smoked a single 3.58% marijuana cigarette was 22 ng/mL using the E.
coli glucuronidase hydrolysis method, whereas THC concentrations using either H.
pomatia glucuronidase or base hydrolysis methods were near zero. Similar differences
were found for 11-OH-THC with a mean concentration of 72 ng/mL from the E.
coli method and concentrations less than 10 ng/mL from the other methods. It is hoped
that the finding of THC in urine may provide a reliable marker of recent cannabis use;
however, adequate data from controlled drug administration studies are not yet available.
7. INTERPRETATION OF BODY FLUID AND HAIR CONCENTRATIONS
Interpreting body fluid concentrations by necessity depends on the nature of the
questions that require a science-based answer; however, the most common social questions
generally can be summarized as: Is the concentration of the drug in an individual’s
body fluid sufficiently high to indicate impairment or place them in violation of a
governing policy?
Research scientists who are conducting studies to determine cannabinoid mechanisms
of action or examine how cannabinoids may be used in clinical treatment also
have an interest in interpreting cannabinoid concentrations in body fluids and tissues.
The generic question they might ask would be: How do fluid or tissue concentrations
in humans correlate with brain concentrations or with treatment outcome? To provide
answers to these important social and scientific questions, we must examine more
closely the kinetics of the drug in bodily fluids and tissues and how these relate to
effects on the individual.
7.1. Plasma
Let us consider the specific example of a man who is stopped by a police officer
for erratic driving. The driver fails a field sobriety test indicating that he is impaired,
and subsequent laboratory testing determines that his plasma THC concentration is
2 ng/mL. Did the THC contribute to his impaired driving?
Plasma concentrations of drug are frequently measured in an attempt to answer
this question because, in general, plasma concentrations of most drugs correlate with
drug effects better than concentrations in other bodily fluids. Mason and McBay
reported in 1985 that one could not predict the effects of cannabis from plasma THC
concentrations (62). They quoted their own study of 600 drivers killed in single-vehicle