Abstract
BackgroundThe phytocannabinoid cannabidiol (CBD) exhibits anxiolytic activity and has been promoted as a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense.MethodsDuring the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged 1 h later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.ResultsCBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex.ConclusionThe CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress.
Highlights
CBD has anxiolytic properties, reducing the autonomic and emotional responses to stress and interfering with the consolidation and extinction of fearful memories [1], which has been associated with anxiety disorders [2], autism spectrum disorder [3], psychosis [4] and post-traumatic stress disorder [5]
While this approach establishes a baseline of resting state blood flow that changes with different task-related paradigms or differs from placebo or healthy controls in response to a preexisting condition, they do not address the effects of repeated exposure or the potential for dose-dependent changes in activity, consistent with drug target specificity
While a majority of Pharmacological MRI (phMRI) studies have been conducted in rats [21], we chose to study mice based on previous work from our group on CBD induced changes in N-acyl-phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) activity [22]
Summary
CBD has anxiolytic properties, reducing the autonomic and emotional responses to stress and interfering with the consolidation and extinction of fearful memories [1], which has been associated with anxiety disorders [2], autism spectrum disorder [3], psychosis [4] and post-traumatic stress disorder [5]. Several studies in humans have used functional BOLD imaging to look at the neuroanatomy affected by treatment with CBD [12,13,14,15,16,17,18,19] These studies looking at the effects of CBD have all evaluated a single oral dose given prior to scanning. While this approach establishes a baseline of resting state blood flow that changes with different task-related paradigms or differs from placebo or healthy controls in response to a preexisting condition, they do not address the effects of repeated exposure or the potential for dose-dependent changes in activity, consistent with drug target specificity. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neu‐ ral circuitry associated with fear and defense
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
