658 M.A. Huestis
AbstractIncreasing interest in the biology, chemistry, pharmacology, and toxicol-
ogy of cannabinoids and in the development of cannabinoid medications neces-
sitates an understanding of cannabinoid pharmacokinetics and disposition into
biologicalfluidsandtissues.Adrug’spharmacokineticsdeterminestheonset,mag-
nitude, and duration of its pharmacodynamic effects. This review of cannabinoid
pharmacokinetics encompasses absorption following diverse routes of adminis-
tration and from different drug formulations, distribution of analytes throughout
the body, metabolism by different tissues and organs, elimination from the body
in the feces, urine, sweat, oral fluid, and hair, and how these processes change over
time. Cannabinoid pharmacokinetic research has been especially challenging due
to low analyte concentrations, rapid and extensive metabolism, and physicochem-
ical characteristics that hinder the separation of drugs of interest from biological
matrices—and from each other—and lower drug recovery due to adsorption of
compounds of interest to multiple surfaces.∆^9 -Tetrahydrocannabinol, the primary
psychoactive component ofCannabis sativa, and its metabolites 11-hydroxy-∆^9 -
tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol are the focus
of this chapter, although cannabidiol and cannabinol, two other cannabinoids with
an interesting array of activities, will also be reviewed. Additional material will be
presented on the interpretation of cannabinoid concentrations in human biological
tissues and fluids following controlled drug administration.
KeywordsCannabinoids · Pharmacokinetics · Tetrahydrocannabinol · Cannabid-
iol · Absorption · Distribution · Metabolism · Excretion · Interpretation · Oral
fluid · Sweat · Hair · Plasma · Urine · Alternate matrix · Marijuana
1
Introduction
Currently, there is a growing interest in the biology, chemistry, pharmacology, and
toxicology of cannabinoids and in the development of potential cannabinoid med-
ications. It is clear that the endogenous cannabinoid system plays a critical role in
physiological and behavioral processes. Endogenous cannabinoid neurotransmit-
ters, receptors, and transporters, synthetic cannabinoid agonists and antagonists,
and cannabis-based extracts are the subject of extensive research. It is hoped that
theseagentsmightprovidenovelapproachestotreathumandiseasesanddisorders.
The therapeutic usefulness of oral cannabinoids is being investigated for medicinal
applications, including analgesia, treatment of acquired immunodeficiency syn-
drome (AIDS)-wasting disease, counteracting spasticity of motor diseases, and the
prevention of emesis following chemotherapy, among others. Cannabis, also, is one
of the oldest and most commonly abused drugs in the world, and its use may have
consequences in terms of pathological and behavioral toxicity. For these reasons,
it is important to understand cannabinoid pharmacokinetics and the disposition
of cannabinoids into biological fluids and tissues. Understanding a drug’s phar-
macokinetics is essential to understanding the onset, magnitude, and duration of
its pharmacodynamic effects.