Grant: Project Grant

The endocannabinoid (eCB) system--the biological system through which THC from cannabis exerts its effects on the bran and body through-- is widely recognized as an important regulator of the stress response. Impairments in eCB signaling both produce activation of stress responses in and of itself, and potentiates the effects of stress exposure, while elevations in eCB signaling are well established to dampen many aspects of the stress response. While there is ample evidence, from rodents to humans, which demonstrates that eCB signaling is an important stress regulatory system, there a notable knowledge gaps regarding where in the brain eCB signaling acts to dampen stress responses. The primary goal of the current proposal will be to determine the mechanisms and processes within the brain by which eCB signaling dampens stress responses. Given that many pharmaceutical companies are developing drugs which target the eCB system as novel treatment approaches to treating stress-related psychiatric illnesses, such as anxiety disorders and post-traumatic stress disorder, understanding how eCB signaling regulates how stress impacts the brain is of significant importance. This proposal will determine the brain sites of action, and neural circuits influenced by eCB signaling, to develop a roadmap of the anti-stress effects of eCB signaling. This research will focus on the amygdala, a brain region important for threat detection and the generation of an anxiety state following stress exposure, as well as the hypothalamus, which coordinates the release of stress hormones after exposure to a challenge. Ultimately these data may be coupled to circuit-specific neuroimaging studies in humans to determine which stress-related illnesses may be particularly benefited by drugs which boost eCB signaling.