Cannabinoids exert many of their activities by binding cannabinoid (CB) receptors. To date, two types of receptors have been identified to have different tissue distribution and mechanisms of signaling. CB₁ receptors are expressed mainly on neurons and glial cells in various parts of the brain, CB2 receptors are found predominantly in the cells of immune system. Both CB₁ and CB₂ receptors belong to the family of G-protein coupled receptors (GPCRs) that, after cannabinoid agonist binding and signaling, exert an inhibitory effect on adenylate cyclaseactivity, activation of mitogen-activated protein kinase, regulation of calcium and potassium channels, and other signal transduction pathways (Munro et al., 1993). Moreover, there is increasing evidence supporting the existence of additional cannabinoid receptors (no-CB₁ and no-CB₂) in both central and peripheral system, identified in CB1 and CB2-knockout mice, involving intracellular pathways that play a key role in neuronal physiology. This kind of receptors includes transient receptor potential vanilloid type 1 (TRPV1), G protein-coupled receptor 55 (GPR55), G protein-coupled receptor 18 (GPR18), G protein-coupled receptor 119 (GPR119) and 5-hydroxytryptamine receptor subtype 1A (5-HT1A) (Pertwee et al., 2010).^Δ9-THC, of which is well-known psychotropic effects, is believed to perform the majority of itsactions in the CNS binding CB₁ and CB₂ receptors. Non-psychotrophic phytocannabinoids exert multiple pharmacological effects via CB₁/CB₂ receptors as well as no-CB₁ and no-CB₂ receptors (Pertwee et al., 2010).

Overall, recent studies showed that cannabinoids inhibit the release of pro-inflammatory cytokines and chemokine in neurological preclinical models suppressing in this way the inflammatory response (Velayudhan et al., 2014). They show also a potent action in inhibiting oxidative and nitrosative stress, modulating the expression of inducibile nitric oxide synthase and reducing the production of reactive oxygen species (ROS) (Velayudhan et al., 2014). Moreover, cannabinoids were found to exert anti-glutamatergic action by inhibiting glutamate release and enhancing the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) (Croxford, 2003). Just about all these properties exhibited by these compounds, have prompted researchers to investigate their potential therapeutic effects in ALS, providing interesting results.