How this cannabinoid interacts with serotonin to promote calm
The secret is out. All over the US (and the world), patients and consumers are zoning in on cannabidiol (CBD) in droves. While policymakers continue to redirect the conversation toward its potential risks, many have already incorporated CBD into their daily medical and wellness regimen. But politicians are not the only ones hitting pause on the giant shiny button that is CBD—it’s researchers, too, although their concerns are quite different.
When it comes to cannabinoid medicine, patient-reported outcomes are far ahead of the science. And that’s thanks of course to long-standing prohibition that has made research on the plant so incredibly difficult. Now that hemp-based CBD is everywhere and medical cannabis programs are growing, researchers are playing catch up on their understanding of the mechanisms underlying the multiple cited benefits of cannabinoids.
Many patients and consumers cite anxiety and stress as a key motivator of their CBD use. In fact, a survey of 2,409 patients found that over 60% reported using CBD for a medical condition, with anxiety cited as one of the top three reasons. 
A state of calm or homeostasis is necessary for the body and mind to work optimally. When this balance is disrupted, agitation or aggression can take over. And anyone who has to commute to an office everyday during rush hour traffic can likely relate to this common feeling. A better understanding of how CBD contributes to calm would greatly advance our understanding of this cannabinoid and how it may treat people with conditions associated with aggression, such as autism spectrum disorder or post-traumatic stress disorder. 
CBD is an attractive compound for the treatment of aggression and irritability as current therapies, including anti-anxiety and anti-psychotic medications, can be very sedating. Since pre-clinical and patient-reported outcomes support CBD as effective for anxiety, researchers in São Paulo utilized an animal model of stress and aggression to evaluate the role of CBD on this behavior.  They also went further to ask how other chemicals in the brain interact with CBD to support these effects.
Researchers administered different CBD doses to mice thirty minutes before they faced a test of aggression.  All doses reduced aggressive behavior and two middle doses further lessened this behavior; importantly, motor activity (a measure of sedation) was not affected by these doses.
Since many anti-depressants work by affecting levels of a chemical in the brain called serotonin, researchers treated mice with compounds that block serotonin and endocannabinoid activity, which reversed the anti-aggressive effects of CBD.  These results suggest that CBD works with serotonin to reduce aggressive behavior. Researchers also found that CBD reduced activity in a part of the brain called the lateral periaqueductal gray, a part of the brain that may play a role in defensive behavior. 
It’s important to remember than mice of course differ from humans. And while these findings are very interesting, these effects must be replicated in clinical trials. However, this study builds off of previous pre-clinical evidence identifying a potential neural circuit underlying the effects of CBD on anxious and aggressive behaviors. And that’s one more step toward less questions about the “legitimacy” of CBD as a medicine.
- Sexton, M, et al. “A Cross-Sectional Survey of Medical Cannabis Users: Patterns of Use and Perceived Efficacy.” Cannabis Cannabinoid Res. vol.1, no.1, 2016 pp. 131-138.
- Hartmann, A, et al. “Cannabidiol Attenuates Aggressive Behavior Induced by Social Isolation In Mice: Involvement of 5-HT1A and CB1 Receptors.” Prog Neuropsychopharmacol Biol Psychiatry. vol.94, 2019, pp. 1-8.
- Motta, S.C., et al. “The Periaqueductal Gray And Primal Emotional Processing Critical to Influence Complex Defensive Responses, Fear Learning And Reward Seeking.” Neurosci Biobehav Rev. vol.76, 2017, pp. 39-47.
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