6. KINETICS
6.1 Absorption by route of exposure
Oral administration
Absorption from the gastrointestinal tract is almost complete.
Peak blood levels and maximal pharmacological effects occur
later after oraladministration than after inhalation (Cone,
198
. Symptoms become apparent within 30 - 120 minutes,
reaching a peak after 2 - 3 hours (Schwartz, 1987; Jaffe,
1985).
Inhalation
After inhalation, peak plasma concentrations are achieved
within a 7 - 10 minutes; subjective effects appear in 20 or 30
minutes but rarely persist for more than 2 - 3 hours.
No data are available on other routes of absorption.
6.2 Distribution by route of exposure
Delta-9-THC is metabolised by the liver. It is intensively
lipophilic and high concentrations accumulate in fatty tissues
in great quantities; these are liberated slowly into the
circulation (Jaffe, 1986).
6.3 Biological half-life by route of exposure
The half-life of delta-9-THC is 3 days. Jaffe (1985) reported
that plasma concentrations of delta-9-THC and 11 hydroxydelta-
9-THC fall rapidly (in a few minutes) due to their
redistribution in the fatty tissues; afterwards there is a
slow decline with a half-life of 30 hours due to the
metabolism and gradual elimination of the drug. The half-life
maybe increased in chronic users to 4.1 days (range 2.9 and
5.0 days) (Johansson, 198
.
6.4 Metabolism
After oral administration but not after inhalation, delta-9-
THC undergoes first-pass hepatic metabolism via enzymatic
hydroxylation and carboxylation to the active metabolite 11-
hydroxy- delta-9-THC, then carboxylation to the more polar
inactive metabolite, 11-nordelta-9-THC acid. Enterohepatic
circulation occurs and only 35% is excreted in the urine.
Around 80 cannabinoid metabolites can be identified from a
similar metabolic pathway; the most important one is 11-
hydroxy-delta-9-THC which is metabolised to non-cannabinoid
metabolites such as terpenes and alkenes.
Delta-9-THC and its metabolites persist in human plasma for
several days or weeks (Jaffe, 1986) but repetitive ingestion
or smoking over weeks is not followed by clinically apparent
accumulation; this suggests that the persistent metabolites
are inactive.
Chronic marihuana smokers metabolise delta-9-THC more rapidly
than non-smokers.
6.5 Elimination by route of exposure
35% of delta-9-THC and its metabolites is eliminated in the
urine compared with 65% in the faeces.
Metabolites can be detected in urine even 2 - 3 days after one
exposure and, in cases of chronic use, after 4 - 5 weeks of
abstinence.
