Marijuana and the Cannabinoids

Human Cannabinoid Pharmacokinetics 209
Fig. 3. Individual plasma ∆ 9 -tetrahydrocannabinol (THC) time course by gas chromatography/mass
spectrometry for six subjects following smoking of a single 3.55%
THC cigarette. (From ref. 30 with permission)
plays mean data for a group of six subjects after paced smoking of a single 3.55%
THC cigarette. The number of puffs, length of inhalation and hold time, time between
puffs, and potency of the cigarette were controlled. Figure 3 shows individual THC
concentration time profiles for six subjects and demonstrates the large intersubject
variability of the smoked route of drug administration. Many individuals prefer the
smoked route, not only for its rapid drug delivery, but also for the ability to titrate
their dose.
In some studies THC was measured in blood, and expected values were found to
be about half those of plasma (31). Albumin and other proteins that bind THC and the
poor penetration of THC into red blood cells contribute to these higher plasma concentrations.
Postmortem blood is a common example where blood concentrations are
routinely reported because of difficulty obtaining acceptable plasma samples. Significant
differences in THC concentrations between the two fluids make it important to
always be informed about which is being reported.
If cannabis is ingested orally, absorption is slower and peak plasma THC concentrations
are lower (25,32–34). Wall et al. found peak THC concentrations approx
4–6 hours after ingestion of 15–20 mg of THC in sesame oil (34). Peak THC concentrations
ranging from 4.4 to 11 ng/mL were observed 1–5 hours following ingestion of
20 mg of THC in a chocolate cookie (25). Oral bioavailability has been reported to be
4–20% (25,34), in part as a result of degradation of drug in the stomach (35). Also,
there is significant first-pass metabolism to active 11-hydroxy-∆ 9 -tetrahydrocannabinol
(11-OH-THC) and inactive metabolites. Plasma 11-OH-THC concentrations range
from 50 to 100% of THC concentrations following the oral route of cannabis adminis-