Healing agents which modulate the cann abinoid program are effective in treating a large number of conditions characterized by inflammation. Furthermore, in neuroinflammatory conditions such as Alzheimer s illness, CB2 receptors MAPK phosphorylation look like substantially up controlled specifically in activated microglia, and selective activation of these receptors blocks the level of characteristic neurotoxic markers. Mice which overexpress human mutant G93A SOD1 protein create a progressive motor neuron illness which is similar to human ALS. In the spinal cords of G93ASOD1 mice, an elevated presence of endocannabinoids fits with presentation of symptoms, and levels continue to turn until the end point of the disease. Pharmacological or genetic top of endocannabinoid levels also somewhat delays disease progression in mice, while having no effect on survival. Management of the non selective incomplete cannabinoid agonists 9 THC or cannabinol are minimally successful in slowing motor disability and prolonging survival in rats after the onset of signs. Last but not least, a current study reported elevated levels of CB2 Eumycetoma receptors in microglia isolated from post-mortem human spinal cords of ALS patients. Collectively, these studies claim that cannabinoid receptors might serve as novel therapeutic targets for ALS drug development. The cornerstone for the beneficial actions of cannabinoids in ALS is not known. Moreover, even though possibly involved in the pathogenesis of ALS, the function and expression of CB1 and CB2 receptors in the G93A mouse model haven’t been determined. Most importantly, particular CB2 agonists, which appear to be most effective for treatment of chronic neuroinflammatory conditions, have yet to be evaluated in rats. Thus, the goal of the present study was to check the hypothesis that in the first stages of disease progression in rats, CB2 receptors are selectively upregulated in spinal cords as a compensatory, protective measure. As a result, daily treatment with CB2 agonists, Letrozole clinical trial even begun as late as indication onset, may notably prolong survival of affected mice. Materials and methods Drugs examined The non-selective CB1/CB2 agonists reviewed in this research were CP 55, 940 cis 3 trans WIN 55, 4 cyclohexanol, pyrrolo benzoxazin yl methanone and HU 210 11 hydroxy delta tetrahydrocannabinol dimethylheptyl. The selective CB1 agonist used was ACEA Deborah eicosatetraenamide. The particular CB1 antagonists used were AM 251 methyl 1Hpyrazole 3 carboxamide and E 2050, tetrahydro trimethyl 6H dibenzopyran. The particular CB2 agonists examined were GW 405833 methanone and AM 1241 methanone. The particular CB2 antagonists used were AM 630, methyl 1 1H indol 3 yl methanone and SR 144528, D heptan 2 yl pyrazole 3 carbo xamide.