In cannabis culture, THC tends to steal the limelight. Many breeders select for strains with higher percentages of THC, due to its psychoactive effect. However, as far as therapeutic applications go, CBD (cannabidiol) seems to be the real leader, calming both joint inflammation and spasticity in epileptic patients. The idea that CBD could also be an anti-depressant or motivator has been mostly overlooked, largely due to the fact that unlike THC, CBD is not as apparently psychoactive. As more evidence comes to light, we are realizing that CBD may in fact have substantial anti-depressive properties while at the same time operating without the risks and negative side effects of current pharmaceutical options.
Sensing potential here, researchers at the Geha Mental Health Center in Israel set out to increase findings on the potential of CBD as a behavioral motivator. To do this, they began by selecting Wistar-Kyoto mice as research subjects. While we normally don’t go into different types of research mice on the Cornerstone blog, in this case, some background is necessary. Wistar-Kyoto mice have genetics that produce behaviors that duplicate many of the classic symptoms of depression found in humans. For instance, these mice are hyper-reactive to stress. Additionally these mice illustrate increased immobility, greater anxiety, and greater amounts of passive coping (such as burying themselves as a defense). This makes these mice a great model of depression and for a research team looking to test potential anti-depressants, a great answer.
To begin, researchers measured individual baseline levels of ability to feel pleasure by applying the “saccharine preference test”. In this test, mice are offered free access to a tank of water, as well as a tank of saccharin (artificial sweetener) mixed with water in a small dose (0.025% mass). Mice then choose freely which to drink from: saccharin water or plain water. The ratio of saccharin consumed to saccharin plus water consumed becomes a sort of ranking that establishes each mouse’s natural preference for pleasure. These levels were recorded twice before the actual CBD experiment to give a reference point to compare the test results of applying CBD.
Next, mice were allowed to explore the elevated plus maze, a standard mouse-research maze constructed with opaque walls. Each mouse was delivered to the center of the maze facing an open hallway and allowed to explore freely for five minutes. Researchers recorded which hallways or “arms” the rodents entered, defining an entrance as all four paws having crossed the threshold. Again, this helped to establish the rodents’ behavior in exploring the maze pre-CBD application.
Finally, mice were given a “novel-object exploration” test. The point of this test is to understand the mouses natural preference between known objects and new objects, which could correlate to how humans deal with new environmental challenges. In this test, mice were allowed to familiarize and become comfortable with a small object such as a stone or screw. They were then placed in an enclosure with that familiar object and a totally new object put on opposite corners of the enclosure, so that researchers could record which object the mice chose to spend time around and for how long.
On testing day, the rats were given CBD in 15, 30, and 45 mg per kg of body weight doses, laced into high-fat diet pellets. Additionally, some of the rodents were given placebo pellets containing no CBD at all. Researchers then repeated the same experiments at two hours after each mouse having consumed the entire pellet, noting any behavioral changes. As a side note for readers, this seems like a reasonable time frame to notice the full effects of CBD, although not necessarily the peak effect, which depends on the metabolism of the mouse or human, as well as the method of consumption.
Results proved fascinating; although no significant changes were seen in activity in the maze, mice receiving a dose of at least 30 mg per kg of body weight showed an increase in saccharin/sweetener preference, which helps restore them to the non-depressed pleasure baseline seen in most other genetic lines of lab mice. Additionally, at 45 mg/kg, mice “spent significantly more time near the [new] object” than those given only the placebo. Mice given less than this dose also showed greater time around the new object, although those results were not statistically significant. Regardless, the trend is important to note because it appears CBD’s effects could be dose-dependent, up to a certain point.
What does this mean? CBD may improve responses to stress, as seen in the “saccharine preference test”, and may also help individuals deal with new stresses better, as seen in the “novel-object exploration” test. Although the cause is unclear, CBD seems to decrease the fear and anxiety over a new object and increase motivation to explore and grow. In a human case, this could translate to reducing social anxiety and in fact, some studies report greater ease of public speaking with CBD. Additionally, unlike THC, CBD has few distracting psychoactive side effects and thus can potentially be used throughout daytime hours. Compared to the often risky and scary side effects of pharmaceutical anti-depressants, this gives us hope that CBD will present a lighter and safer alternative for individuals suffering from chronic depression or lack of motivation.
Gal Shoval, Liat Shbiro, Liron Hershkovitz, et al. Prohedonic Effect of Cannabidiol in a Rat Model of Depression. Neuropsychobiology (2016) 73:123-129. DOI: 10.1159/000443890