The effects of phytocannabinoids in stroke and pharmacology of CBD and TMP co-application in cellular models

In an ever ageing population, stroke represents a growing burden on society. After the age of 55, the likelihood of experiencing a stroke increases two-fold. People in this age group are also at a substantially higher risk of developing a disability following a stroke. Numerous studies have demonstrated the involvement of the endocannabinoid system in modulating molecular disturbances associated with stroke. Thus phytocannabinoids that modulate the endocannabinoid system may represent a novel strategy for treating a stroke. A Meta-analysis was conducted to collate the data of relevant studies in the area of cannabidiol (CBD) mediated protection in animal models of stroke. A search of existing literature identified two separate laboratories both using focal ischemic-reperfusion injury (8 articles) induced by middle cerebral artery occlusion, to assess the efficacy of CBD. CBD administered intraperitoneally in male ddY mice (n: control 70, CBD 68) reduced infarct volume by a mean difference of 29.60 mm3 (Cl [34.94, 24.26], p<0.00001) and CBD administered via intracerebroventricular injections in adult male Wistar rats (n: control 81, CBD 81) reduced infarct volume by a mean of 88.62 mm3 (Cl [101.98, 75.26], p<0.0001). Publication bias was evident (p=0.004), and median study quality was 2 (range 0-4/10). Eggers statistic suggested publication bias was evident and negative studies were missing. The results of the meta-analysis indicated more robust evidence was needed to form any meaningful conclusions surrounding the efficacy of CBD in animal models of stroke. The results from the previous chapter prompted an in vivo investigation into the effects of CBD and cannabidiolic acid (CBDA) in a mouse model of stroke. CBD and CBDA had no significant effect on infarct volume 24 h following permanent middle carotid artery occlusion (pMCAO). An indirect measurement of vasogenic swelling was made, which showed CBD at 1 mg/kg increased brain water content by 7.6% ± 2.6, 95% CI [-5.9, 8.1] (p