171 Indeed, treatment of postsymptomatic, 90-day-old SOD1G93A mice (a model of ALS) with WIN 55,212-2, significantly delayed disease progression. Furthermore, genetic ablation of the FAAH enzyme, which results in raised levels of the endocannabinoid anandamide, prevented the appearance

of disease signs in these mice. Surprisingly, elevation of cannabinoid levels with either WIN 55,212-2 or FAAH ablation had no effect on life span. Ablation of the CB1 receptor, in contrast, had no effect on disease onset in these mice, but significantly extended life span. Together these results show that cannabinoids have significant Inhibitors,research,lifescience,medical neuroprotective effects in this model of ALS, and suggest that these beneficial effects may be mediated by nonCB1 receptor mechanisms.172 THC was also found to delay the progression of disease.173,174 Treatment

with AM1241, a CB2-selective Inhibitors,research,lifescience,medical agonist, was effective at slowing signs of disease progression, when administered after onset of signs in an ALS mouse model. Administration at the onset of tremors delayed motor impairment in treated mice when compared with vehicle controls175; moreover, AM-1241 prolonged survival in these mice.176 In a survey among ALS patients, cannabis was reported to be moderately effective in reducing symptoms of appetite loss, depression, pain, spasticity, and drooling.177 Cannabinoids were also proposed to have a role in Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical the treatment of Alzheimer’s disease (AD). THC competitively inhibits acetylcholinesterase (AChE) and prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of AD.178 THC treatment also decreased severity of disturbed behavior, and this effect persisted during the placebo period in patients who had received THC.179 Compared with baseline, THC led to a reduction in nocturnal motor activity These findings were corroborated by improvements in the Neuropsychiatrie Inventory total score, as well as in subscores for agitation, aberrant motor, and nighttime behaviors; no side effects were observed.180 Studies on cannabinoid anticonvulsant

activity Inhibitors,research,lifescience,medical began in 1975, when CBD, and four CBD derivatives, (CBD-aldehyde-diacetate, 6-oxo-CBD-diacetate, 6-hydroxy-CBD-tri-acetate and 9-hydroxy-CBD-triacetate) were shown to protect Selleckchem MK 8776 against maximal electroshock convulsions in mice, to potentiate pentobarbital for sleeping-time and to reduce spontaneous motor activity.181 Later additional CBD analogs were shown to be active182-184 CBD was found to be an effective anticonvulsant with specificity more comparable to drugs clinically effective in major, but not in minor seizures. Furthermore, it appears that CBD enhances the anticonvulsant effects of drugs in major seizures and reduces their effects in minor seizures.185,186 Hence, CBD was suggested as a drug for the treatment of children with pharmacoresistant epilepsy.