Table 2.

Cannabinoid receptors (CBRs) ligands and their effects shown in different animal models of MS (pertinent references are in parenthesis).

Structure and Name	Origin and Activity	Animal Model and Effects
∆9-THC	Phytocannabinoid CB1R partial agonist	In EAE rats: amelioration of EAE progression [100]. In CREAE mice: amelioration of tremor and spasticity [102].
∆8-THC	Phytocannabinoid CB1R ligand	In EAE rats: amelioration of the clinical manifestations of EAE [101].
WIN-55212	Synthetic cannabinoid CB2R agonist	In CREAE mice: amelioration of tremor and spasticity [102]. In TMEV-infected mice: improvement of motor function on established neurological symptomatology; stimulation of the remyelination; reduction of microglial activation and of the number of CD4+ infiltrated T cells [105].
JWH-133	Synthetic cannabinoid CB2R agonist	In CREAE mice: amelioration of tremor and spasticity [102]. Intrathecal administration in EAE mice: reduction, dose-dependently, of both mechanical and cold hypersensitivity without any signs of ataxia or sedation [108].
Methanadamide	Endocannabinoid CB1R/CB2R agonist	In CREAE mice: amelioration of tremor and spasticity [102].
Palmitoylethanolamide (PEA)	Endocannabinoid CB1R/CB2R agonist	In CREAE mice: transient inhibition of spasticity [102].
Arachidonyl-2-chloroethylamide (ACEA)	Synthetic cannabinoid CB1R agonist	In TMEV-infected mice: improvement of motor function on established neurological symptomatology; stimulation of the remyelination; reduction of microglial activation and of the number of CD4+ infiltrated T cells [105].
JWH-015	Synthetic cannabinoid CB2R agonist	In TMEV-infected mice: improvement of motor function on established neurological symptomatology; stimulation of the remyelination; reduction of microglial activation and of the number of CD4+ infiltrated T cells [105].
O-1966	Synthetic cannabinoid CB2R agonist	In the chronic EAE model: improved motor function; reduction of rolling and adhesion of endogenous leukocytes to pial microvasculature [106].
Gp-1a	Synthetic cannabinoid CB2R agonist	In EAE mice: reduction of clinical scores; amelioration of the recovery [107].
compound 21	Synthetic cannabinoid CB2R agonist	In EAE mice: reduction of the clinical scores and symptoms; decrease of leukocyte infiltration in the spinal cord and demyelination in white matter [109].
PM-226	Synthetic cannabinoid CB2R agonist	In TMEV-infected mice: dampening of neuroinflammation; reduction of microglial activation [110,111].
compound 57	Synthetic cannabinoid CB2R agonist	In EAE mice: alleviation of the clinical symptoms of EAE; protection of the murine central nervous system from immune damage; reduction of leukocyte infiltration and demyelination [112].
VCE-004.8	Synthetic cannabinoid CB2R agonist	In EAE and TMEV mice: immunomodulatory activity; inhibition of inflammatory chemokines, chemokines receptors, and cytokines; inhibition of the expression of adhesion molecules (VCAM and ICAM-1); induction of the expression of the hypoxia-inducible factor (HIF) [113].
β-caryophyllene (BCP)	Phytocannabinoid CB2R agonist	In EAE mice: reduction of mechanical hyperalgesia, inflammation and pain [115].