3. Umbruch 4.4..2005 - Online Pot

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tory processes due to activated immune cells entering the CNS [119, 120].
This explains why current therapies addressed to delay disease progression
include basically immunomodulatory agents (i.e. substances targeted against
immune elements, such as interferon, glatiramer or mitoxantrone [179]).
However, recent evidence also supports the ultimate occurrence of excitotoxicity
and neurodegeneration (oligodendrocyte death and axonal loss) in this disease
[121, 180–182]. It is for this reason that cannabinoids, in addition to their
well-described relieving effects on specific symptoms in MS [127–130, 183],
might be also used as neuroprotectant molecules to delay/arrest disease progression
by protecting oligodendrocytes from death and by reducing axonal
degeneration [76, 183, 184].
As regards the symptom-relieving effects of cannabinoids in MS, most of
the studies have focused in the management of pain and motor-related symptoms
such as spasticity, tremor and dystonia (for review see [76, 183]). They
have tried to provide solid experimental support to previous anecdotal, uncontrolled
or preclinical data that suggested a beneficial effect for marijuana when
smoked by MS patients to alleviate specific symptoms such as spasticity, dystonia,
tremor, ataxia, pain and others (for review see [76, 183]). This has been
the basis for a clinical trial recently completed in the UK, which has proved
that cannabinoids did not have a beneficial effect on spasticity in MS patients,
but increased the patient’s perception of improvement for different signs of
this disease [185]. In animal studies, a series of studies by Baker and coworkers
revealed a potent anti-spasticity effect of plant-derived, synthetic and
endogenous cannabinoid agonists in a mouse model of MS, chronic relapsing
experimental autoimmune encephalomyelitis (CREAE) [127–130]. They also
demonstrated that these effects were mediated by cannabinoid CB 1 and, to a
lesser extent, CB 2 receptors [127]. Using this mouse model, they have also
described anti-spastic effects of compounds that are able to inhibit the process
of termination of the biological action of endocannabinoids [128–130]. These
data were concordant with the increase in endocannabinoid levels recorded in
the brain and, in particular, in the spinal cord of these animals [128]. The
chronic administration of plant-derived cannabinoids [186, 187] or specific
endocannabinoid-uptake inhibitors [188] may also reduce or delay the incidence
and severity of clinical signs in rats with experimental autoimmune
encephalomyelitis (EAE), a monophasic model of MS where only inflammation
takes place. However, the amelioration of experimental MS in this rat
model is presumably due to the fact that cannabinoid agonists acted either as
immunosuppressive agents, by preventing the accumulation of inflammatory
cells in the CNS [186, 187], or by exerting a direct anti-inflammatory effect
[188]. Beneficial effects of cannabinoids have been also reported by other
authors [189, 190] in a MS mouse model generated by infection with the
Theiler’s murine encephalomyelitis virus. In these animals, cannabinoid agonists
produced an improvement of motor function, and reduced activated
microglia and promoted remyelination in the spinal cord [189], so cannabinoids
might provide beneficial effects in MS that would go beyond symptom