Abstract
The present review synthetically describes the currently advanced hypotheses for a neurobiological basis of depression, ranging from the classical monoaminergic to the more recent neurotrophic hypothesis. Moreover, the Authors review the available preclinical and clinical evidence suggesting a possible role for the endocannabinoid system in the physiopathology of depression. Indeed, in spite of the reporting of conflicting results, the pharmacological enhancement of endocannabinoid activity at the CB1 cannabinoid receptor level appears to exert an antidepressant-like effect in some animal models of depression. On the contrary, a reduced activity of the endogenous cannabinoid system seems to be associated with the animal model of depression, namely the chronic mild stress model. Moreover, a few studies have reported an interaction of antidepressants with the endocannabinoid system. With regard to clinical studies, several authors have reported an alteration of endocannabinoid serum levels in depression, while post mortem studies have demonstrated increased levels of endocannabinoids associated to a concomitant hyperactivity of CB1 receptor in the prefrontal cortex of suicide victims. No clinical trials carried out using cannabinoids in the treatment of affective disorders have been published to date, although anecdotal reports have described both antidepressant and antimanic properties of cannabis as well as the ability of cannabis to induce mania that has also been documented. These findings are discussed, leading us to conclude that, although data available are sufficient to suggest a possible involvement of the endogenous cannabinoid system in the neurobiology of depression, additional studies should be performed in order to better elucidate the role of this system in the physiopathology of depression.
Highlights
The present paper provides a synthetic review of the current neurobiological hypotheses of depression, taking into account preclinical and clinical evidence suggesting a possible involvement of the endogenous cannabinoid system in the physiopathology of depression
No clinical trials performed using cannabinoids in the treatment of affective disorders have been published to date, anecdotal reports have described both antidepressant and antimanic properties of cannabis
Preclinical data were derived exclusively from studies performed in animal models of depression, the majority of which used the rat forced swimming test model of depression, reporting largely conflicting results
Summary
The present paper provides a synthetic review of the current neurobiological hypotheses of depression, taking into account preclinical and clinical evidence suggesting a possible involvement of the endogenous cannabinoid system in the physiopathology of depression. It has been reported that chronic fluoxetine causes an up-regulation of CB1 receptors in the Prefrontal cortex (PFC), [78,79], chronic DMI up-regulates CB1 receptors in the hypothalamus and hippocampus [78,79], tranylcypromine (a MAOI) decreases the levels of Gobshtis et al [82] have demonstrated that the antidepressant -like effect produced by DMI and fluoxetine in the mice forced swimming test was not antagonized by SR141716A. Koethe et al[101] found a decrease of CB1 receptor density in the glial cells of the grey matter in the brain of post-mortem patients suffering from major depression
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have