CristinaBenito,1JuanPabloRomero,1,2RosaMarı ´aTolo ´n,1DiegoClemente,3Fabia ´nDocagne,3CeciliaJ.Hillard,4
1LaboratoriodeApoyoalaInvestigacio ´n,Fundacio ´nHospitalAlcorco ´n,28922Madrid,Spain,2DepartmentofBiochemistry,FranciscodeVitoria
Increasing evidence supports the idea of a beneficial effect of cannabinoid compounds for the treatment of multiple sclerosis (MS).
fatty acid amide hydrolase (FAAH) enzyme in brain tissue samples obtained from MS patients. Areas of demyelination were identified
and classified as active, chronic, and inactive plaques. CB1and CB2receptors and FAAH densities and cellular sites of expression were
against the CB1receptor with antibodies against type 2 microtubule-associated protein, myelin basic protein, and the platelet-derived
positive) in MS plaques. Specifically, CB2-positive microglial cells were evenly distributed within active plaques but were located in the
flammatory conditions, selective glial expression of cannabinoid CB1and CB2receptors and FAAH enzyme is induced in MS, thus
Cannabis sativa preparations have been used for ?4000 years for
recreational and medicinal purposes, but the mechanistic char-
acterization of some of its constituent chemicals, the “cannabi-
Felder, 2001). To date, two cannabinoid receptors have been
cloned, the CB1and the CB2receptors (Matsuda et al., 1990;
Munro et al., 1993). In addition, several endocannabinoids
have been identified, most important among them are N-
arachidonoylethanolamine [anandamide (AEA)] and 2-arachi-
donoylglycerol (Mechoulam et al., 1998). These endocannabi-
noids are synthesized and released on demand and, after release,
are removed from their sites of action by cellular uptake pro-
cesses. The endocannabinoids are metabolized intracellularly by
fatty acid amide hydrolase (FAAH) and monoglyceride lipase,
among other enzymes (Bisogno et al., 2005).
Currently, the endocannabinoid system (ECS) is a target for
the treatment of several diseases, including multiple sclerosis
(MS) (Pryce and Baker, 2005). Clinical evidence confirms the
therapeutic potential of cannabinoids in the treatment of symp-
toms of MS. A randomized, placebo-controlled trial in which
patients with both stable MS and muscle spasticity were treated
ticity using objective measures, although patients reported im-
provements (Zajicek et al., 2003). Patients who continued ?9-
in objective measures of spasticity (Zajicek et al., 2005). Patients
also reported a reduction in pain together with improvements in
mobility (Zajicek et al., 2005). Another clinical trial using the
oromucosal spray Sativex (a combination of ?9-THC and can-
nabidiol) to treat central neuropathic pain syndromes attribut-
able to MS showed that this preparation produced a significant
reduction in pain and sleep disturbances (Rog et al., 2005).
ThisworkwassupportedbyMinisteriodeEducacio ´nyCienciaGrantSAF2004-00237andComunidadAuto ´noma
contributionofMontserratDı ´az-Meco,AnaBele ´nRebolledo,andCarolinaHerranzaregratefullyacknowledged.
Correspondence should be addressed to Julia ´n Romero, Laboratorio de Apoyo a la Investigacio ´n, Fundacio ´n
HospitalAlcorco ´n,28922Alcorco ´n/Madrid,Spain.E-mail:firstname.lastname@example.org.
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