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Introduction

Anxiety and depression are conditions that affect people from all walks of life negatively, impacting their social lives, productivity, health and the overall quality of life. In extreme cases, depressive-like conditions lead to death. Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa that has shown great psychiatric potential with strong anti-depressant and anxiolytic properties. As a result, scientists have been busy trying to figure out if CBD can be used as a novel agent for combating depressive conditions. They have also been grappling with its mechanisms of action. This article is an introductory summary of all the available research and case studies with regards to the use of CBD for depression.

The Endocannabinoid System and its Role in Mood and Related Conditions

The endocannabinoid system (ECs) is a neuroactive lipid signaling system widely distributed throughout the brain and other major organs. It has been shown to modulate numerous functions in our bodies. For instance, the ECS is heavily involved with emotional behavior, mood and stress responsiveness as shown by post mortem and other studies.

The growing evidence of reports now show that deficits in endocannabinoid signaling may be the cause of depressive and anxiogenic behavioral responses. Furthermore, there is proof that the increase of endocannabinoid signaling through external cannabinoids such as CBD can result to both anti-depressive and anxiolytic behavioral responses.

As for the cause of depression and other mood disorders, CBD has also been giving scientists a new insight. Many now believe that abnormalities in the CNR1 gene that codes for CB1 receptors to be the root cause for various psychiatric disorders. Let us take a brief look at the studies below.

CBD for Depression: What the Evidence Says

Besides depression, CBD has been showing potential therapeutic effects for a wide range of illnesses. These include serious conditions such as epilepsy, Parkinson’s disease, inflammation, skin conditions, neurodegeneration,, Alzheimer’s disease, just to name a few. For a full list of conditions that scientists have been trying to cure using CBD, go to this page.

At first, the many pharmacological properties of CBD seemed too good to be true. However, after the discovery of the endocannabinoid system which spans throughout the body, including the brain, scientists have been slowly putting the pieces of the puzzle together.

Take a look:

A review of animal model studies testing for CBD’s anti-depressive-like properties

A study was carried out with the aim to review other studies of animal models that tested CBD’s anxiolytic and antidepressant properties. After reviewing all the data, the authors noted that CBD portrays strong anti-anxiety and antidepressant effect in animal models. Other experiments with CBD demonstrated non-activation of CB1 and CB2 neuro-receptors, hence suggesting that the compound uses other mechanisms of action to bring about its therapeutic effects, such as interaction with the 5-HT1A neuro-receptor.

CBD as an Antidepressant
Another study set the objective to examine whether CBD was an effective and safe anxiolytic agent and potentially also an antidepressant. They used 48 of the ‘depressive-like’ Wistar-Kyoto (WKY) rats as their models, and gave each 5, 30 and 45 mg/kg of CBD periodically. They then used the saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test for analysis.

They found out that CBD showed a prohedonic effecton the WKY rats at 30 mg/kg in the SPT. In the NOE test, CBD increased exploration and locomotion of the models at 45 mg/kg and also increased locomotion at 15 mg/kg.

These results indicate an improvement in the naturally-low motivation levels of WKY rats to explore their surroundings. There was no similar results at any dose in the EPM test. These findings serve as the first to show CBD as an antidepressant in animal modelsand pushes forward the limited knowledge on CBD for depression. They researchers concluded that CBD could represent a novel treatment for clinical depression and other states with extreme anhedonia.

Another study sought to test the hypothesis that CBD would have antidepressant-like effects in male Swiss mice as evaluated using the forced swimming test (FST). They also tested whether these responses (if any) depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neuro-trophic factor (BDNF).

The results showed that 30 mg*kg(-1) of CBD treatment reduced immobility time in the FST test, same as the prototype antidepressant imipramine. CBD portrayed these effects without changing exploratory behavior in the open field arena. The CBD treatment did not change BDNF levels in the hippocampus. The authors concluded that CBD induces antidepressant-like effects similar to those induced by imipramine. Furthermore, these properties seemed to have been mediated by activation of 5-HT(1A) receptors.

Scientists know that depression is a major risk factor for cardiovascular conditions. However, the underlying mechanisms remain uncertain. Since recent preclinical proof suggest that endogenous agonists of endocannabinoid receptors such as CBD and THC are involved in both cardiovascular operation and depression. With that in mind, a group of scientists initiated a test to find out whether CBD correlated with either in humans.

The scientists found out that endocannabinoids play a major role in regulating blood pressure specifically in depressed individuals with higher blood pressure. Furthermore, the results strongly suggest that there is an interrelationship among endocannabinoids, depression and cardiovascular risk factors, especially in women.

How CBD interacts with the Endocannabinoid System to Cause Antidepressive-like Effects

In recent years, the endocannabinoid system has been largely implicated in both the pathogenesis of depression as well as the action of antidepressants. As a result, several advances have been made in order to determine its exact role in the etiology of depression and the practical actions of antidepressant drugs.

Some studies have shown that a deficiency in endocannabinoid signaling is enough to produce “depressive-like” characteristics at the preclinical level. These include changes in the reward system, emotional and cognitive behaviors, as well as biological changes such as, impaired stress adaptation, reduced neurogenesis etc. This signaling deficiency is also capable of inducing symptoms of depression in humans at a clinical level.

Cannabidiol (CBD), the main non-psychotomimetic component of Cannabis interacts with the endocannabinoid system to manifest anxiolytic-like properties in many behavioral tests. Nonetheless, CBD’s mechanism of action of to combat depression remains unclear.

One important study evaluated the effects of CBD on depression after administering acute and chronic doses using the olfactory bulbectomy (OBX) mouse in order to investigate its underlying mechanism. The researchers used open field and sucrose preference behavioral tests as well as microdialysis and autoradiography of 5-HT1A receptor functionality studies after treatment with CBD. The pharmacological antagonism of the effects of CBD were also investigated in order to understand its true mechanism of action.

The results showed that CBD exhibits fast and sustained antidepressive-like effectsas demonstrated by the reversal of the OBX-induced hyperactivity and anhedonia in the models. In vivo micro dialysis proved that CBD significantly enhanced serotonin and glutamate levels in vmPFCx. Moreover it effected these changes differently, based on the emotional state of the model and the duration of the treatment. The scientists observed that both antidepressive-like effects and improved cortical 5-HT/glutamate neurotransmission brought about by CBD were inhibited by 5-HT1A receptor blockade. Furthermore, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also noted after application of chronic CBD.

To conclude, these results show that CBD could serve as a unique and fast antidepressant drug. CBD exerts these effects by enhancing both serotonergic and glutamate cortical signaling via a 5-HT1A receptor-dependent mechanism.

Conclusion

From both human and animal model studies, there has been undeniable proof that CBD exhibits anti-anxiety and antidepressant effects. As shown above, most of the experiments concerning CBD for depression demonstrated little activation of neuroreceptors CB1 and CB2 as it was earlier believed. On the contrary, most of the studies showed a good interaction between CBD and the 5-HT1A neuro-receptor. Although more research is needed before CBD for depression treatments can be available, these studies represent crucial steps toward this goal.

Below is a list of all the current studies concerning the use of CBD for depression.

 

Research and Case Studies on the effects of Cannabis to treat Depression: