Authors:
Fernández-Ruiz J, Sagredo O, Pazos MR, García C, Pertwee R, Mechoulam R, Martínez-Orgado J.
Abstract:
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for
numerous disorders exerted through molecular mechanisms that are yet to
be completely identified. CBD acts in some experimental models as an
anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic
and antipsychotic agent, and is therefore a potential medicine for the
treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and
nausea, anxiety and schizophrenia, respectively. The neuroprotective
potential of CBD, based on the combination of its anti-inflammatory and
anti-oxidant properties, is of particular interest and is presently
under intense preclinical research in numerous neurodegenerative
disorders. In fact, CBD combined with Δ(9)-tetrahydrocannabinol is
already under clinical evaluation in patients with Huntington’s disease
to determine its potential as a disease-modifying therapy. The
neuroprotective properties of CBD do not appear to be exerted by the
activation of key targets within the endocannabinoid system for
plant-derived cannabinoids like Δ(9)-tetrahydrocannabinol, i.e. CB(1)
and CB(2) receptors, as CBD has negligible activity at these cannabinoid
receptors, although certain activity at the CB(2) receptor has been
documented in specific pathological conditions (i.e. damage of immature
brain). Within the endocannabinoid system, CBD has been shown to have an
inhibitory effect on the inactivation of endocannabinoids (i.e.
inhibition of FAAH enzyme), thereby enhancing the action of these
endogenous molecules on cannabinoid receptors, which is also noted in
certain pathological conditions. CBD acts not only through the
endocannabinoid system, but also causes direct or indirect activation of
metabotropic receptors for serotonin or adenosine, and can target
nuclear receptors of the PPAR family and also ion channels.