676 M.A. Huestis
Fig. 5.Predictive mathematical models for estimating the elapsed time in hours (Hrs) of last cannabis use
basedonplasma∆^9 -tetrahydrocannabinol(THC)and11-nor-9-carboxy-∆^9 -tetrahydrocannabinol(THCCOOH)
concentrations. (Reproduced from theJournal of Analytic Toxicology, by permission of Preston Publications,
a division of Preston Industries; Huestis et al. 1992c, Fig. 1 therein)
plasma THC (Mason and McBay 1984). Interpretation is further complicated by
residual THC and THCCOOH concentrations found in blood of frequent cannabis
users. In general, it is suggested that chronic cannabis smokers may have residual
plasma THC concentrations of less than 2 ng/ml 12 h after smoking cannabis (Peat
1989). Significantly higher residual concentrations of THCCOOH may be found.
Having an accurate prediction of the time of cannabis exposure would provide
valuable information in establishing the role of cannabis as a contributing factor
to events under investigation. Two mathematical models for the prediction of time
of cannabis use from the analysis of a single plasma specimen for cannabinoids
were developed (Huestis et al. 1992c). Model I was based on THC concentrations
and model II was based on the ratio of THCCOOH to THC in plasma (Fig. 5).
Both correctly predicted the times of exposure within the 95% confidence interval
for more than 90% of the specimens evaluated. Furthermore, plasma THC and
THCCOOH concentrations reported in the literature following oral and smoked
cannabis exposure, in frequent and infrequent cannabis smokers, and with mea-
surements obtained by a wide variety of methods, including radioimmunoassay
and GC/MS, were evaluated with the models. Plasma THC concentrations less than
2.0 ng/ml were excluded from use in both models due to the possibility of residual
THC concentrations in frequent smokers. Manno et al. evaluated the models’ use-
fulness in predicting the time of cannabis use in a controlled cannabis smoking
study (Manno et al. 2001). The models were found to accurately predict the time
of last use within the 95% confidence intervals. Due to the limited distribution
of THC and THCCOOH into red blood cells, it is important to remember that
when comparing whole blood THC and/or THCCOOH concentrations to plasma
concentrations, it is necessary to double the whole blood concentration prior to
comparison.