Major Depressive Disorder (MDD) or Clinical Depression is a mental disorder characterized by a persistent feeling of sadness and a lack of interest in activities previously perceived as enjoyable. MDD is diagnosed in people of all ages, adults being the most affected group, and it affects more than 264 million people worldwide. MDD origin and development depend on biological, psychological, environmental, and genetic factors, and treatments often include medications, psychotherapy, and electric brain stimulation techniques. Unfortunately, given the complexity of the disorder, there is no one-size-fits-all medication, medication will showcase a distinctive array of positive and/or negative effects depending on the individual. Currently, a commonly overlooked target by physicians to treat MDD is the endocannabinoid system which it’s been known to modulate emotional homeostasis.
A study led by the University of the Balearic Islands in Spain performed post-mortem studies (also known as autopsy) on former patients suffering from MDD being either treated with antidepressants or being left untreated. They measured the amount of CB1 and CB2 receptors in the prefrontal cortex and in cortical layers of the brain and compared them with healthy controls. Herein, the researchers found a significant increase in the expression of CB1 receptors in both the prefrontal cortex and the cortical layers of the brain in both groups of patients suffering from MDD when compared to the healthy controls. However, they found no significant differences in the expression of CB2 receptors between subjects in neither areas of the brain.
On the other hand, a study led by the Federal University of Santa Catarina in Brazil investigated the anti-depressive effects of Terpineol, a terpenoid found in essential oils of various plants including Cannabis. First, they showed through computer modeling simulations that Terpineol has a high affinity to bind to the CB1 and CB2 receptors, and also to the D2 dopaminergic receptor. Then, the researchers used an in vivo model (research done with or within a whole, living organism) for depression to evaluate the anti-depressive effects of Terpineol on rodents. They found that 200 mg/kg of Terpineol effectively inhibited depressive-like behavior in rodents and validated that Terpineol acted through the CB1, CB2, and the D2 dopaminergic receptor.
MDD currently represents a global burden without an accurate treatment for the general population. Each person has a unique reaction to each medication available, therefore, people suffering from MDD need to be carefully prescribed for antidepressants by their physician. Moreover, given the lack of efficiency in precision medicine, patients also need to explore an array of medications before they encounter the one that benefits them the most. As a result, additional attention must be given to Cannabinoids as a viable treatment to MDD given their ability to interact not only with the endocannabinoid system but also with adjacent systems known to effectively prevent and treat MDD.
Salort, G., Hernández-Hernández, E., García-Fuster, M. J., & García-Sevilla, J. A. (2020). Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder. Journal of Affective Disorders, 276, 626–635. https://doi.org/10.1016/j.jad.2020.07.074
Vieira, G., Cavalli, J., Gonçalves, E. C. D., Braga, S. F. P., Ferreira, R. S., Santos, A. R. S., … Dutra, R. C. (2020). Antidepressant-like effect of terpineol in an inflammatory model of depression: Involvement of the cannabinoid system and D2 dopamine receptor. Biomolecules, 10(5). https://doi.org/10.3390/biom10050792
