At this point, you’re no stranger to the buzz about cannabidiol (CBD), one of over a hundred compounds produced by the plant cannabis sativa. Like its well-known sibling, THC, CBD is a phytocannabinoid and targets numerous systems in the brain and body. However, unlike THC, CBD won’t get you high. Although CBD can act on the same brain targets as THC, it does so in opposite ways. CBD even has its own unique set of brain targets. In fact, because there are so many potentially therapeutically relevant CBD targets, there’s a growing number of pre-clinical (i.e., using lab rodents, but not humans) and clinical research studies into CBD’s medicinal effects. If you’re considering incorporating CBD into your routine, it’s important to understand how CBD affects your brain and the body to promote a sense of calm.
At different doses, CBD can act on over 65 targets in the brain and body. But it’s important to understand that not every one of these targets is affected at a given dose. Instead, as CBD levels in one’s body rise, so do the number of affected targets. Studies show that once you find the optimal dose, increasing that dose can sometimes make CBD less effective. Identifying one’s “Goldilocks Zone” may require a bit of experimentation, and it’s important to remember that more is not always better.
While CBD has many targets, animal studies have helped reveal not only if CBD works, but how by identifying several important targets that may relate to CBD’s benefits.
Although CBD hits a number of targets simultaneously, it’s the endocannabinoid and serotonin systems in particular that work to reduce anxiety. In fact, some of the earliest studies of CBD and animals focused on its anxiety-reducing effects. They found that CBD at low-to-moderate doses reduced anxiety-like behavior in rats and mice; at higher doses, however, these effects were lost. Similarly in humans, moderate doses of CBD, but not high doses, reduced anxiety in public speaking tests.
These benefits are believed to be mediated by CBD’s ability to activate the brain receptor for serotonin, 5-HT1A. Serotonin may sound familiar as it’s a primary target in common treatments for anxiety and depression. Selective serotonin reuptake inhibitors (also known as SSRIs), pharmaceutical drugs commonly prescribed for depression and anxiety, work by increasing levels of serotonin available to activate these receptors. CBD does so directly.
CBD’s benefits likely come from its multiple actions on different brain systems working together to promote calm and relaxation. CBD has been shown to help manage anxiety and the body’s stress response by helping to normalize the activity across numerous regions of the brain, including the amygdala and hypothalamus. In lab animals, these effects are associated with CBD's ability to increase levels of serotonin and anandamide, two brain chemicals that are believed to improve mood and induce a sense of calm.
Additional reading: Millar, S. A., et al. (2018). A systematic review on the pharmacokinetics of cannabidiol in humans. Frontiers in Pharmacology, 9.
Josh Kaplan, Ph.D., is an Assistant Professor of Behavioral Neuroscience at Western Washington University where he runs a laboratory studying the developmental consequences and therapeutic benefits of cannabis. He is a passionate communicator of cannabis science and has contributed to numerous publications including Leafly and HighTimes, from which he was named in the Top 100 Most Influential People in Cannabis in 2018.