Disturbances in mood and depression are famously associated with serotonin signalling. CBD activates the 5-HT1A receptor, which stimulates serotonergic neurones affecting mood.
Mood disorders are complex and involve a range of neurotransmitter and signalling pathways. At the root of many signalling pathways are the endocannabinoids. Your endocannabinoid system is a homeostatic regulator of neurotransmitter systems and just about every other physiologic system in the body.
CBD can influence endocannabinoid signalling and therefore other neurotransmitters, such as glutamate. This is excitatory in nature and is closely associated with anxiety responses. Indirect inhibition of glutamate signalling (via endocannabinoid activity) might also contribute to the anti-anxiety effects of CBD.
When we talk about neurotransmitters binding receptors, we have to look at a given molecule's affinity for that receptor. Take CB receptors for example; CBD is a partial agonist of the CB receptors, with a weak affinity for it. THC however is a full agonist with strong affinity (it's more attracted to that receptor), which may explain some of CBD’s subtle effects on mood when compared to THC, which has full-blown psychoactive effects.
That's why the addition of THC is often synergistic with CBD, as an even more effective means of treating depression and anxiety. In the right ratios, they can be a power couple for altering mood.
Anyway, CBD can actually change the shape of the GABA-A receptor in a way that increases its affinity for its specific target neurotransmitter – GABA. Gamma-Aminobutyric acid is an inhibitory neurotransmitter that produces states of calm and balance throughout the nervous system and is what accounts for the sedating and relaxing qualities of alcohol. Through a greater affinity for GABA-A receptors, the relaxing qualities of GABA are more pronounced, alleviating anxiety.
In addition, a more recent understanding of mood disorders, such as depression and anxiety has emerged. These share a common underpinning which you may be familiar with – inflammation.
Neuroinflammation is found in a host of mental illnesses which affect mood, including depression, anxiety and even bipolar disorder and schizophrenia. This inflammation actually affects a host of communication networks within the brain, messing with mood.
More good news – CBD is a potent anti-inflammatory and has antioxidant properties which make it an effective neuroprotective.
TPRV-1 is a receptor that is well associated with pain perception and inflammation. CBD may act to desensitise you to pain, and quite possible exert its anti-inflammatory effects through this receptor (as well as CB2 receptor activity, which ‘talks’ to the immune system).
The limbic system is a key regulator of mood and stress. The hippocampus, as part of this system, is also of great interest in anxiety. Conditions of chronic stress can impair the neural plasticity within the hippocampus, and produce symptoms of depression and anxiety. This might explain the co-existence of these two mood disorders, as stress induces depression.
What is neural plasticity?
It's basically the brain's ability to adapt to new situations and environments and respond to injury and disease through the development and maintenance of neural networks.
A key regulator of neural plasticity, Brain-Derived Neurotropic Factor (BDNF) can be measured as a serum and plasma reading which is typically found to be reduced in cases of depression. BDNF is a crucial component in the growth and development of new neural networks in the brain – neurogenesis.
I bet you're guessing what role Cannabis has to play here, right?
Well, it's a corker, I'llthat tell you that.
Anandamide is actually very closely associated with BDNF. In fact when you exercise you are increasing Anandamide signalling, thereby stimulating BDNF to work its magic on the hippocampus. This is why exercise is such a powerful anti-anxiety therapy.
In a similar way to exercise, CBD prevents the metabolism and re-uptake of Anandamide, allowing increased endocannabinoid signalling and possibly BDNF presence. In this way, neurogenesis can occur in the hippocampus.
CBD encourages increased binding of Anandamide to produce this effect, and exercise independently increases Anandamide signalling. Together, these could be powerful anti-anxiety treatments.
