If you’re a patient suffering from stress or anxiety, there’s good news: researchers are making interesting new in-roads into the biological mechanisms capable of alleviating these conditions.  A recent report published in the medical journal Biology of Mood & Anxiety Disorders sheds light on the effects cannabis use might have on alleviating stress and anxiety by focusing on endogenous cannabinoids (eCBs) found in cannabis and their respective brain receptors. A growing body of evidence has shown that this system plays crucial roles in managing stress, anxiety, and stress-related psychiatric illness.

So far, one of the most useful approaches to understanding the eCB system has been to utilize genetically modified mice. In this approach, researchers delete genes that produce cannabinoid receptors, rendering the mice unable to absorb/use cannabinoids. Scientists have found that these mice exhibit a trend of high anxiety, impaired stress coping, and stress-induced psychopathology (gauged by accepted benchmark tests for rodents). While these effects seem to depend on what part of the brain and what specific neurons the receptors are attached to, the overwhelming trend is that mice lacking receptors also perform poorly, which implies that the eCB system is an essential part of stress and anxiety management.

Another useful approach has been investigating chemical inhibitors that slow the rate of the enzymes (FAAH and MAGL) that naturally dispose/recycle eCBs. This approach is similar to many commercially available anti-depressants: the pill itself does not contain serotonin (the lack of which has been related to mood disorder), but rather a chemical that allows your natural serotonin to function longer before being destroyed, therefore increasing the level in your brain. As expected, scientists found that inhibiting eCB destruction in mice (therefore increasing eCBs available) decreased anxiety and depression. This result is particularly interesting; it not only corroborates the genetic evidence, but also suggests that in the future, cannabis related treatment may focus less on consuming more cannabinoids and more on allowing the body to better retain its natural ones.

The results in humans are less clear, hampered by ethical limits of medicine. Originally noticing the way eCBs stimulated appetite, scientists developed a weight-loss drug that blocked eCB uptake, releasing it on the market as Rimonabant. Unfortunately, around a third of patients experienced significant psychiatric side effects, to the degree that it had to be pulled from the market. With this reaction well-documented, further testing of eCB blockades seems harmful and therefore unlikely to be pursued. However, that unfortunate accident gave us strong proof (a sample of 18,000 patients) that disrupting eCB receptors brings on a host of psychological issues, which in turn again implies that the eCB system is key to healthy brain function.

While humans can’t be genetically modified, we can always observe those with minor genetic mutations (polymorphism) that correspond to eCB production and uptake. So far this data has hinted that individuals who produce higher levels of eCBs are depression-resistant and stress-resistant and vice-versa, which fits with clinical data. However, the particular nature of genetics, specifically that a mutated gene can sometimes operate identically to a non-mutated one, makes it difficult to prove a direct connection.

By measuring levels of actual eCBs in the body (ligands that bind to receptors), we are able to confirm that for individuals without an eCB response to stressful situations, cortisol (the body’s primary stress response/marker) is much more abundant. This is noticed in many individuals with PTSD, hinting that the future of treatment for similar disorders may involve the eCB system.

Outside of specific findings, all of this research is collectively confirming that the eCB system plays a vital natural role in our bodies, shifting focus away from the purely serotonin-based model of emotional response we generally ascribe psychiatric illness to. This understanding allows us to consider novel, more complete treatments for those suffering from complex disorders. Although it seems prudent to resist unfounded hype or portray cannabis as a magic bullet, medical research is confirming biological evidence for the properties that millions find useful every year.

 

Source:

Hill and Patel: Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses. Biology of Mood & Anxiety Disorders 2013 3:19.

Image: Tufts Universtiy