Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.
Angelo A. Izzo1, 4, , Francesca Borrelli1, 4, Raffaele Capasso1, 4, Vincenzo Di Marzo2, 4 and Raphael Mechoulam3
D9-tetrahydrocannabinol binds cannabinoid (CB1 and
CB2) receptors, which are activated by endogenous com-
pounds (endocannabinoids) and are involved in a wide
range of physiopathological processes (e.g. modulation
of neurotransmitter release, regulation of pain percep-
tion, and of cardiovascular, gastrointestinal and liver
functions). The well-known psychotropic effects of D9-
tetrahydrocannabinol, which are mediated by activation
of brain CB1 receptors, have greatly limited its clinical
use. However, the plant Cannabis contains many can-
nabinoids with weak or no psychoactivity that, thera-
peutically, might be more promising than D9-
tetrahydrocannabinol. Here, we provide an overview
of the recent pharmacological advances, novel mechan-
isms of action, and potential therapeutic applications of
such non-psychotropic plant-derived cannabinoids.
Special emphasis is given to cannabidiol, the possible
applications of which have recently emerged in inflam-
mation, diabetes, cancer, affective and neurodegenera-
tive diseases, and to D9-tetrahydrocannabivarin, a novel
CB1 antagonist which exerts potentially useful actions in
the treatment of epilepsy and obesity
Angelo A. Izzo1, 4, , Francesca Borrelli1, 4, Raffaele Capasso1, 4, Vincenzo Di Marzo2, 4 and Raphael Mechoulam3
D9-tetrahydrocannabinol binds cannabinoid (CB1 and
CB2) receptors, which are activated by endogenous com-
pounds (endocannabinoids) and are involved in a wide
range of physiopathological processes (e.g. modulation
of neurotransmitter release, regulation of pain percep-
tion, and of cardiovascular, gastrointestinal and liver
functions). The well-known psychotropic effects of D9-
tetrahydrocannabinol, which are mediated by activation
of brain CB1 receptors, have greatly limited its clinical
use. However, the plant Cannabis contains many can-
nabinoids with weak or no psychoactivity that, thera-
peutically, might be more promising than D9-
tetrahydrocannabinol. Here, we provide an overview
of the recent pharmacological advances, novel mechan-
isms of action, and potential therapeutic applications of
such non-psychotropic plant-derived cannabinoids.
Special emphasis is given to cannabidiol, the possible
applications of which have recently emerged in inflam-
mation, diabetes, cancer, affective and neurodegenera-
tive diseases, and to D9-tetrahydrocannabivarin, a novel
CB1 antagonist which exerts potentially useful actions in
the treatment of epilepsy and obesity