Cannabidiol and Depression

Studies and peer-reviewed research into the effects of CBD and Depression

Depression

Endocannabinoid system dysfunction in mood and related disorders  

From the abstract

We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement.

Antidepressant-Like and Anxiolytic-Like Effects of CBD

From the abstract:

Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.

 

The endocannabinoid system and the treatment of mood and anxiety disorders   

From the abstract

 

The central endocannabinoid system is a neuroactive lipid signalling system in the brain which acts to control neurotransmitter release. The expression patterns of this system throughout limbic regions of the brain ideally situate it to exert regulatory control over emotional behaviour, mood and stress responsivity. A growing body of evidence unequivocally demonstrates that deficits in endocannabinoid signalling may result in depressive and anxiogenic behavioral responses, while pharmacological augmentation of endocannabinoid signalling can produce both antidepressive and anxiolytic behavioral responses. The aim of this review is to summarize current knowledge of the role of the endocannabinoid system in the etiology and treatment of mood and anxiety disorders, such as depression, anxiety and post-traumatic stress disorder. Collectively, both clinical and preclinical data argue that cannabinoid receptor signalling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders.

 

Endocannabinoid signaling in the etiology and treatment of major depressive illness 

From the abstract:

 

The purpose of this review is to examine human and preclinical data that are relevant to the following hypotheses. The first hypothesis is that deficient CB1R-mediated signaling results in symptoms that mimic those seen in depression. The second hypothesis is that activation of CB1R-mediated signaling results in behavioral, endocrine and other effects that are similar to those produced by currently used antidepressants. The third hypothesis is that conventional antidepressant therapies act through enhanced CB1R mediated signaling. Together the available data indicate that activators of CB1R signaling, particularly inhibitors of fatty acid amide hydrolase, should be considered for clinical trials for the treatment of depression.

 

Antidepressant-like effects of cannabidiol in mice: Possible involvement of 5-HT1A receptors  

From the abstract:

 

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).

 

Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants  

From the abstract:

 

In the last few years, there have been several advances in the determination of the role of the endocannabinoid system in the etiology of depression and the functional actions of antidepressant drugs. Specifically, a deficiency in endocannabinoid signaling is sufficient to produce a “depressive-like” phenotype at the preclinical level (including changes in rewarding, emotional and cognitive behavior and biological changes such as increased HPA axis activity, impaired stress adaptation, reduced neurogenesis and altered serotonin negative feedback), and capable of inducing symptoms of depression in humans at a clinical level. In line with these findings, clinical populations diagnosed with depression are found to have reduced levels of circulating endocannabinoids and preclinical models of depression reveal a deficit in central endocannabinoid signaling. Moreover, facilitation of endocannabinoid signaling is sufficient to produce all of the behavioral and biochemical effects of conventional antidepressant treatments. Further, many forms of antidepressant treatments significantly alter endocannabinoid signaling, and in some of these cases this recruitment of endocannabinoid signaling is involved in the neuroadaptive effects of these treatments. Ultimately, these data present a compelling picture of the putative role of the endocannabinoid system in the processes subserving both the development and treatment of depression.

 

Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa  

From the abstract:

 

The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.

 

Antidepressant-like and anxiolytic-like effects of CBD  

From the abstract:

 

Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.

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