Boosting endocannabinoids in the hippocampus prevented both cardiovascular and anxiety responses to stress in rats

The FAAH inhibitor URB597 injected into the dorsal hippocampus prevented stress-induced cardiovascular responses (heart rate increase, blood pressure rise, temperature drop) and delayed anxiety. The CB1 antagonist AM251 exacerbated cardiovascular stress responses and blocked URB597's protective effects.

In vivo pharmacology in rats using intra-hippocampal injections of CB1 antagonist AM251 and FAAH inhibitor URB597 before acute restraint stress. Cardiovascular parameters measured during stress; elevated plus maze for anxiety assessed 24 hours post-stress.

This reveals the hippocampal endocannabinoid system as a dual regulator of both the physical and psychological responses to stress. A single molecular target in one brain region controls both the immediate cardiovascular reaction and the delayed anxiety that follows.

Stress-related disorders often feature both cardiovascular symptoms and anxiety, and this study shows the endocannabinoid system connects them at the hippocampal level. This could explain why some people find cannabis helps with stress and may point toward more targeted therapeutic approaches.

Acute stress model in rats with direct brain injection. Does not model chronic stress exposure. Only male rats used. Human hippocampal endocannabinoid function may differ. Drug delivery route is not clinically practical.