660 M.A. Huestis
2
Pharmacokinetics of THC
2.1
Absorption
2.1.1
Smoked Administration
Route of drug administration and drug formulation determine the rate of drug
absorption. Smoking, the principal route of cannabis administration, provides
a rapid and efficient method of drug delivery from the lungs to the brain, con-
tributing to its abuse potential. Intense pleasurable and strongly reinforcing effects
may be produced due to almost immediate drug exposure to the central nervous
system. Slightly lower peak THC concentrations are achieved after smoking com-
pared to intravenous administration (Ohlsson et al. 1980). Bioavailability following
the smoking route was reported as 2% to 56%, due in part to the intra- and inter-
subject variability in smoking dynamics that contribute to uncertainty in dose
delivery (Agurell et al. 1986; Agurell and Leander 1971; Ohlsson et al. 1982, 1985).
The number, duration, and spacing of puffs, hold time and inhalation volume, or
smoking topography, greatly influences the degree of drug exposure (Azorlosa et
al. 1992; Heishman et al. 1989; Perez-Reyes 1990). Expectation of drug reward also
may affect smoking dynamics. Cami et al. noted that subjects were able to change
their method of smoking hashish cigarettes to obtain higher plasma concentra-
tions of THC when they expected to receive active drug in comparison to placebo
cigarettes (Cami et al. 1991).
Fig. 1. Mean (n=6)plasmaconcentrationsof∆^9 -tetrahydrocannabinol (THC), 11-hydroxy-∆^9 -
tetrahydrocannabinol(11-OH-THC),and11-nor-9-carboxy-∆^9 -tetrahydrocannabinol(THCCOOH)duringsmok-
ing of a single 3.55% THC cigarette.Each arrowrepresents one inhalation or puff on the cannabis cigarette
(M.A. Huestis, unpublished data)