| dc.description.abstract | There have been numerous studies reporting that cannabinoids, both exogenous
and endogenous, have a potential beneficial function during incidences of
neurological damage. Using gene knockout mice and cannabinoid-selective agents,
this study demonstrates the diverse actions of cannabinoids with a particular focus
on experimental autoimmune encephalomyelitis, an animal model of multiple
sclerosis. The results presented here report on the action of stimulators of
cannabinoid receptors in the nervous system (CNS) on; immune function, as a
mechanism of suppressing autoimmune attack of the central nervous system, as
agents to suppress neurodegenerative events leading to disease progression and as
agents that can control signs of disease that occur as the consequences of
autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the
psychoactive component in cannabis and the CB1 cannabinoid receptor appears to
be central to many of the therapeutic actions of cannabis but also to the side-effect
potential of cannabinoid drugs. This study reports on methods to avoid
psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists
whilst exploiting the therapeutic potential of the cannabinoid system in order to
control spasticity. This was achieved by targeting mechanisms of endocannabinoid
degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore,
this study also reports the development of novel cannabinoid compounds that are
excluded from the brain and inhibit spasticity and also demonstrates the
mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This
study provides further evidence for the efficacy of cannabinoid compounds during
an ongoing CNS disease and also their efficacy for treating the consequences of
CNS autoimmune disease, which hopefully, will give additional impetus for further
clinical investigations of cannabinoid agents in not only multiple sclerosis but also
other neurodegenerative diseases of the CNS. | en_US |
