The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years. Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite,
analgesia and anti-
emesis have lead to the medicinal application of cannabis. Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a
neuroprotective effect of the cultivar. The discovery of the psychoactive component of cannabis resin,
Delta(9)-tetrahydrocannabinol (Delta(9)-THC) occurred long before the serendipitous identification of a
G-protein coupled receptor at which
Delta(9)-THC is active in the brain. The subsequent finding of endogenous
cannabinoid compounds, the synthesis of which is directed by neuronal excitability and which in turn served to regulate that excitability, further widened the range of potential
drug targets through which the
endocannabinoid system can be manipulated. As a result of this, alterations in the
endocannabinoid system have been extensively investigated in a range of
neurodegenerative disorders. In this review we examine the evidence implicating the
endocannabinoid system in the cause, symptomatology or treatment of
neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of
endocannabinoid-based
therapies in each disease context.