Researchers say the findings could be an important discovery for conditions which affect memory, such as Alzheimer’s disease and post-traumatic stress disorder (PTSD), and could help better target therapies.
In the study, published in the Journal of Psychopharmacology, researchers set out to investigate how CBD influences cerebral blood flow in different regions on the brain involved in memory processing.
In human mesenteric arteries, we have very recently shown that CBD causes vasorelaxation of U46619 and endothelin-1 pre-constricted arterial segments (Stanley & O’Sullivan, 2012, under review). In human mesenteric arteries, CBD-induced vasorelaxation has a pEC50 in the mid-micromolar range which is similar to that observed in rat mesenteric arteries. However, CBD-induced vasorelaxation in human arteries has a maximal response of ∼40% reduction of pre-imposed tone. We went on to show that CBD-induced vasorelaxation in human mesenteric arteries is endothelium-dependent, involves CB1 receptor activation and TRPV channel activation, nitric oxide release and potassium hyperpolarization ( Figure 1 ) (Stanley & O’Sullivan, 2012, under review).
Direct vascular effects of CBD
The acute vascular effects of cannabinoid compounds have been well studied in a range of models. In a variety of in vivo and in vitro models, phytocannabinoids and endogenous cannabinoids (endocannabinoids) have been shown to cause vasorelaxation. However, the potency, efficacy and mechanisms of action often differ. For example, early work in rabbit cerebral arteries showed that THC and the endocannabinoid anandamide (AEA) caused vasorelaxation that was dependent on cyclooxygenase (COX) activity . Later, Randall et al.  showed AEA-induced vasorelaxation in the perfused rat mesenteric bed that was inhibited by antagonism of the CB1 receptor and inhibition of potassium hyperpolarization. The vasorelaxant effects of AEA in rat arteries are also dependent on the vessel size in that the maximal response to AEA is greater in small resistance vessels and includes an endothelial-dependent component that is not observed in larger arteries . In rat aortae, the vasorelaxant response to AEA is not sensitive to CB1 antagonism or TRPV1 desensitization, but is sensitive to Gi/o protein inhibition using pertussis toxin (PTX) . Further differences in cannabinoid effects can be found when comparing the same arterial bed of differing species. In rabbit aortae, AEA causes greater maximal relaxation than observed in rat aortae through a SR141716A (1 µ m ) sensitive pathway which is dependent on the endothelium . It has also been shown that cannabinoid responses are dependent on the cannabinoid compound used. For example, the endocannabinoids AEA and N-arachidonoyl-dopamine (NADA) cause similar degrees of vasorelaxation in rat aortae, but by different mechanisms . These studies highlight the complexity of acute vasodilator actions of cannabinoids on the vasculature (for a full review see ).
Vascular effects of cannabinoids
Taken together these studies show that in vitro and in vivo, using cell culture, isolated tissue and animal models, CBD has been demonstrated to reduce the negative effects of high glucose, diabetes and inflammation on the vasculature and on vascular hyperpermeability. As yet, the receptor sites of action for CBD in some of these studies remain unclear, but a common theme is the reduction in inflammatory markers (see Table 1 ).