Marijuana and the Cannabinoids

Human Cannabinoid Pharmacokinetics 219
The Huestis and Cone study examined infrequent cannabis users and did not
address excretion patterns that one would expect from chronic use. As mentioned,
chronic users take longer than infrequent users to eliminate marijuana metabolites.
This is a result of the disposition of THC into poorly perfused tissues such as fat. With
chronic cannabis use, THC concentrations in these poorly perfused compartments
increase, forming less accessible depots of THC in the body. Hunt and Jones demonstrated
that the slow return of THC from these depots into the plasma was the ratelimiting
step in the terminal elimination of THC from the body (36). Fraser and Worth
studied a group of 26 chronic marijuana users, testing both the Manno and Huestis
criteria for new use and had a false-negative rate of 7.4% with the Huestis guideline
and 24% with the Manno rule (93). They extended the study to include 37 chronic
marijuana users with at least 48 hours between specimens; with the >0.5 cutoff, new
drug use was identified in 80–85% of cases (94). Of course, the smaller the ratio used,
the greater the potential for false-positive results. The reasons for conducting the urine
test, i.e., treatment or parole, and the impact of the results on the donor guide the
choice of which ratio to apply.
Based on this valuable scientific information, we can answer the question about
whether the individual on parole in our example had smoked marijuana between
donating the specimen containing 100 ng/mL THCCOOH and the specimen with
150 ng/mL THCCOOH. The answer is that we cannot tell if he used cannabis in violation
of his conditions for parole. Additional information is needed to differentiate
between new cannabis use and residual drug excretion. This spike in urine concentration
would not be unusual for an individual who had complied with his treatment
protocol. If the treatment center had collected the specimens at least 24 hours apart
and had measured creatinine concentrations, we would have additional information to
provide a more definitive answer. If the outcome of the evaluation could be used to
place the individual, who was a former chronic cannabis user, in prison for continuing
use after entering his rehabilitation program, the higher ratio of 1.5 might be a better
choice for evaluating his urine tests. This would achieve better specificity, rather than
sensitivity. In addition, more frequent monitoring may be useful if urine specimens
are being collected more than 48 hours apart.
7.3. Oral Fluid
Oral fluid is composed of saliva and secretions from the nasopharyngeal area
and mouth. Mechanisms of drug entry into oral fluid are not fully understood. Scientists
have determined that passive diffusion from blood and tissue depots and direct
entry into oral fluid following smoked, oral, sublingual, or snorted routes of drug
administration are the primary sources. In rare cases (e.g., lithium), active transport
mechanisms also may contribute. Some of the factors affecting how much drug enters
oral fluid from the blood are the lipophilicity of the drug, the degree of plasma protein
binding, the drug’s pK a , and pH differences between blood and oral fluid. In general,
if the drug is not extensively bound to plasma proteins, is lipophilic, and is present in
an unionized state, passive diffusion is the primary mechanism for drug entry into oral
fluid. The lower pH in oral fluid as compared with blood can result in ion trapping of
drugs with a higher pK a (e.g., codeine), which has concentrations three to four times