Pharmacological Actions of Cannabinoids 3Fig. 1.The structures of four plant cannabinoids,∆^9 -THC,∆^8 -THC, cannabinol and cannabidiol
Fig. 2.The structure of nabilone
ume). Because of its high lipid solubility and low water solubility,∆^9 -THC was
long thought to owe its pharmacological properties to an ability to perturb the
phospholipid constituents of biological membranes (reviewed in Pertwee 1988).
However, all this changed in the late 1980s with the discovery in mammalian tissues
of specific cannabinoid receptors.
Two types of cannabinoid receptor have so far been identified (reviewed in
Howlett et al. 2002). These are CB 1 , cloned in Tom Bonner’s laboratory in the USA
in 1990, and CB 2 , cloned by Sean Munro in the UK in 1993. Both these receptors
are coupled through Gi/oproteins, negatively to adenylate cyclase and positively
to mitogen-activated protein kinase. CB 1 receptors are also coupled through Gi/o
proteins, positively to A-type and inwardly rectifying potassium channels and
negatively to N-type and P/Q-type calcium channels and to D-type potassium
channels. In addition, there are reports that CB 1 and CB 2 receptors can enhance
intracellular free Ca2+concentrations (Fan and Yazulla 2003; Rubovitch et al. 2002;
Sugiura et al. 1996, 1997, 2000). It is unclear whether this enhancement is Gi/o