3. Umbruch 4.4..2005 - Online Pot

Cannabinoids in neurodegeneration and neuroprotection 85
ical event in the pathogenesis, such as PD [4–6]. However, it must be noted
that these antioxidant properties of specific cannabinoids would be certainly
CB 1 receptor-independent [37, 55–57]. This antioxidant capability has been
proposed to explain the neuroprotective effects that ∆ 9 -THC and other related-cannabinoids
showed in animal models of cerebral ischemia ([58, 59]; see
[4–6] for review). Hampson et al. [56], using cultures of rat cortical neurons
exposed to toxic levels of glutamate, also found that both ∆ 9 -THC and CBD
provided neuroprotection, via a CB 1 receptor-independent mechanism, presumably
based on the antioxidant properties of both compounds, which are relatively
equivalent.
Cannabidiol is a plant-derived cannabinoid that presents an interesting pharmacological
profile, comparable to that previously mentioned for HU-211 (see
above). CBD is non-psychoactive, because does not bind significantly to CB 1
receptors. However, it exhibits an antioxidant potency comparable, and, even
superior, to that of classic dietary antioxidants such as ascorbate and α-tocopherol
[56]. CBD was equivalent to ∆ 9 -THC as an antioxidant compound, but
it would be more advantageous than ∆ 9 -THC for a potential clinical use
because it can be used at higher doses and for longer times than those possible
with ∆ 9 -THC, due to its lack of psychoactivity. An additional advantage for
CBD is that its use in prolonged treatment does not induce tolerance [60], a
phenomenon often observed with ∆ 9 -THC [61]. On the other hand, it should
be mentioned that recent evidence suggests that CBD might also act by blocking
endocannabinoid uptake, thus increasing endocannabinoid levels [62], or
by binding to hypothetical CBD receptors [63] still waiting to be isolated
and/or cloned. All these properties, but particularly its antioxidant potential,
enable CBD to be used as a neuroprotective compound, with minimal psychotropic
side effects, against the brain damage produced by reactive oxygen
species in brain ischemia [56] and also in several chronic neurodegenerative
diseases (see [64] and details below). In this sense, we have recently found that
in rat models of PD, either ∆ 9 -THC or CBD are able to delay/arrest the progression
of neuronal death [64]. It is possible that they might also be effective
in HD, as suggested by preliminary evidence [65], since it has been demonstrated
that production of free radicals, originated as a consequence of a mitochondrial
dysfunction, is one of the major cytotoxic events that takes place
during the pathogenesis of this motor disorder (see [66] for review).
Anti-inflammatory properties of cannabinoids
Another mechanism potentially linked to various chronic and acute brain degenerative
pathologies is the activation of inflammatory processes. Inflammation
may induce or aggravate brain damage through increasing the release of neurotoxic
mediators, such as TNF-α, interleukin (IL)-1β, IL-6, eicosanoids, NO and
reactive oxygen species. Alternatively, it could enhance the neuronal vulnerability
to these cytotoxic stimuli. These factors are predominantly produced by