Thus, there remains a clear need for further studies of the structure-activity
relationships and mechanisms of action of CBD-based formulations to ensure that
the therapeutic indices of dosage formulations are clearly understood and optimized
for patient populations.
11.1 Introduction
Cannabidiol (CBD, Fig.11.1) is an extremely lipophilic bicyclic phytocannabinoid
that is concentrated in the oil-filled glandular trichomes of certain varieties of the
Cannabis sativaplant (Turner et al. 1981 ). It is biosynthetically produced from
cannabigerolic acid through the action of cannabidiolic-acid synthase (Taura et al.
2007 ). By this pathway, the aryl carboxylic acid (i.e., cannabidiolic acid, or CBDA)
is initially formed, and it readily decarboxylates to CBD over time and during
heating (e.g., drying) or combustion (e.g., smoking) of plant material.
The synthesis (Petrzilka et al. 1967 ; Baek et al, 1985 ) and X-ray crystal struc-
tures (Jones et al. 1977 ; Ottersen et al. 1977 ) of CBD have been described, and a
variety of structural analogs and metabolites have been synthesized and tested for
pharmacological activity (Hanus et al. 2005 ). The energetically favorable orienta-
tion of the terpene ring is almost perpendicular to the aromatic ring, which deviates
from the relatively coplanar orientation of the tricyclic structure of the primary
psychoactive phytocannabinoid in cannabis,D^9 -tetrahydrocannabinol (D^9 -THC).
The perpendicular orientation of the terpene ring in CBD has been suggested to
sterically interfere with cannabinoid receptor binding (Thomas et al. 1991 ; Reggio
et al. 1993 ).
As with many phytocannabinoids, the high lipophilicity and poor aqueous sol-
ubility of CBD results in variable absorption after oral administration, which can be
affected by the vehicle or dosage formulation. Because it accumulates in fat and
lipids, CBD has an extended terminal half-life of several days after oral dosing
(Consroe et al. 1991 ). Despite their structural differences, the metabolism of CBD
Structure:Compound Names: Cannabidiol; (-)-trans-Cannabidiol, CBD
Chemical Abstract Name: 2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-
pentyl-1,3-benzenediol
CAS Number: 13956-29-1
Molecular Formula: C 21 H 30 O 2
Molecular Wt.: g/mol (average)314.4617 314.2245 g/ml (monoisotopic)Fig. 11.1 Chemical structure of cannabidiol
250 B.F. Thomas