Depression will affect many of us in our lifetime. Some of us are genetically predisposed, others become depressed as a result of the hard knocks of life, while many struggle to find an answer as to why they experience low mood. One factor emerging as a possible biological cause is an imbalance in the endocannabinoid system, with studies suggesting it could be both a potential biomarker of depression and a therapeutic target. And with cannabis being the most studied method of stimulating the endocannabinoid system, could compounds in the plant like CBD, be the depression treatment of the future?
Depression – A Personal Experience Needs Personalised Medicine
Depression is described as a medical illness causing “feelings of sadness and/or a loss of interest in activities once enjoyed.” It’s unknown how many people are affected, with estimates suggesting that anywhere between 25% – 50% of the population will be depressed at some point in their lives. Either way, even in the 21st century, a stigma still exists, and in the US 80% of people who are clinically depressed are currently receiving no specific treatment. Those that do receive help may be prescribed antidepressants, receive psychotherapy or combination of both.
Due to the unique combination of factors that contribute to each case of depression: a genetic predisposition, chronic or elevated stress levels, illness, bereavement, trauma or medication, it’s generally accepted that a one-size-fits-all approach will only yield moderate effects. As such, scientists and doctors are increasingly exploring a personalised approach, where every aspect of the patient is considered – from their biological makeup to environmental influences.
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Endocannabinoid Imbalance – A Cause Of Depression?
The term ‘chemical imbalance’ is often cited as potential cause of depression and mental illness, referring to an over or under production of neurotransmitters such as serotonin and dopamine. But there’s another key neurotransmitter that may also play a part. Anandamide, one of the primary endocannabinoids in the body, has also been found to be dysregulated in cases of depression, with scientists researching how a dysfunctional endocannabinoid system may be involved in depressed states.
The endocannabinoid system (ECS) is a complex network of receptors and cannabis-like ligands (Anandamide and 2-AG) found throughout the body. There are two primary receptors: CB1 which are mostly located in the brain and central nervous system, and CB2 receptors found in the immune system, peripheral nervous system, and gut. The system’s modus operandi is to bring homeostasis or balance to our bodies and minds, and it has been likened to a dimmer switch, turning up and down activity in the body when needed.
In cases of depression and mental illness, scientists are most interested in studying the relationship between the CB1 receptors and the endocannabinoids that activate them. They have observed how the ECS is involved in regulating the activity of neurotransmitters known to be involved in emotional processing such as reward, fear, memory extinction and stress. It would follow then that too much or too little endocannabinoid activity would affect these key factors in mental health and could be possible biomarkers for future vulnerability to depression.
Endocannabinoid Changes Found In Depression
It’s no coincidence that scientists named the first endocannabinoid they discovered, anandamide. Coming from the Sanskrit word for bliss, they knew that the neurotransmitter was intricately linked to feelings of happiness and wellbeing. While anandamide levels are difficult to measure as it is produced on demand, mood enhancing activities such as cardiovascular exercise have been seen to give it a temporary boost.
Not only that, studies show people with a genetic mutation in which they produce less of the enzyme that breaks anandamide down in the body (FAAH), are generally happier and cope with stress better.
2-AG, the other key endocannabinoid, also shows signs of dysregulation in depressed states. In a study carried out on women with depression, 2-AG was found to be significantly lower, with levels further diminishing the longer the depression lasted. 2-AG is further found to be below normal in cases of PTSD.
But it’s not just the endocannabinoids scientists are interested in studying when it comes to depression. Another indication of a fully functioning ECS is the density of the CB1 receptors in the brain.
So far, studies have been carried out on animal models or in post mortems of depressed patients. Unfortunately, it’s not as straightforward as saying that in all instances the ECS is depleted. While across the board, there appears to be changes in CB1 receptor density compared to non-depressed subject, research shows that this density varies depending on the area of the brain.
On rodent models, the act of blocking CB1 signalling brought about depression like symptoms such as reduced interest in rewards such as sex, food, sleep disruption and increased anxiety. The suggestion being that there is a direct link between reduced CB1 density and depression.
However, in another study on depressed mice, increased CB1 density was observed in the Prefrontal Cortex, the area of the brain responsible for decision making, development of personality, and modulating social behaviour. Scientists believe that this heightened ECS activity rather than being the cause of the depression, is the body’s attempt to mitigate the symptoms of depression and chronic stress.