Major depression, often called Major Depressive Disorder (MDD) is one of the most common psychiatric disorders in the United States and around the world. The burden it places on individual’s personal lives and careers is severe. Although there are both pharmacological and nonpharmacological treatments, they are not always successful in symptom treatment or alleviation. It is therefore compelling to find an alternative therapeutic approach to major depression that will be better-tolerated, safe and effective.
What is Major Depressive Disorder (MDD)?
MDD is a psychiatric condition characterized by persistent and troubling symptoms including:
- Feelings of sadness
- Hopelessness
- Lose of interest in activities once enjoyed
- Changes in appetite and sleep
- Feelings of worthlessness
- Difficulty concentrating
- Recurrent thoughts of death
- Suicidal actions
MDD is a terribly debilitating illness that affects the individuals’ physical, mental, emotional, social and occupational or academic life. Simple, everyday tasks like cleaning the house, running errands or paying bills become very challenging to perform. Unfortunately, the condition is also highly associated with suicide and according to the CDC, there is a completed suicide in the U.S. every 11 minutes.
Pathogenesis of Depression
One way to grasp the underlying physiological mechanisms of suicide is to examine pathophysiological models of Major Depressive Disorder (MDD). One such pathway involves monoamine neurotransmitters including serotonin, noradrenaline and dopamine). Simply put, it has been believed for some time that these neurotransmitters play a major role in suicidal thoughts and actions.
The stress-sensitive hypothalamic-pituitary-adrenal (HPA) axis is another area of concern regarding the development of depression and suicidal thoughts and actions. According to one article, “…chronic HPA axis dysfunction has been observed in 40-60% of patients subject to chronic stress, leading to sustained cortisol release, decreased rhythmicity and insufficient glucocorticoid receptor regulatory feedback inhibition”1. The severity of depression may therefore be the result of high and sustained cortisol levels.
Another more recent concept – the neuroinflammation hypothesis, suggests that due to the imbalance between pro-inflammatory and anti-inflammatory cytokines, dysfunction occurs in the immune system which then results in the gradual development of depression.
Depression and the Endocannabinoid System
All humans and animals possess an endocannabinoid system (ECS), which not only regulates most bodily functions, but is deeply involved in neurological pathways, like the HPA, neurotransmitters and other important systems outside of the ECS. “Research indicates that the endocannabinoid system significantly contributes to the development and etiology of depression”.1 Moreover, the ECS influences cognitive functioning, motivation, emotional response, sleep quality and the stress response.
CBD, The ECS and Depression: What’s the Connection?
Research has discovered various effects of CBD within the endocannabinoid system and their combined effects on depression, in both animal and human studies. Experiments performed over the past 40 years on animals have shown CBD’s anxiolytic (anti-anxiety) and anti-depressant results. One study reported that “The evidence indicates a comparable effect between CBD and some anti-depressants in a single or combined administration (fluoxetine or desipramine) modulating serotonergic pathways dependent on 5-HT1A receptor activation”.2
In human clinical trials, the use of FDA-approved cannabinoid-based medication, Sativex, was tested in a double-blind, randomized study in patients with chronic pain. The medication not only significantly reduced pain, but it improved mood as well.3 Results of another study show that daily oral administration of CBD can induce restorative effects of areas of the brain thereby reducing depressive and psychotic symptoms in regular cannabis users.4
Other, research-based effects of CBD and its interaction within the ECS on depression include:
- Reduced depressive symptoms
- Improvement in attention
- Enhanced verbal learning
- Increased memory
Final Thoughts on Major Depression, CBD and the Endocannabinoid System
Among the many neuropsychiatric disorders, major depression or MDD is one of the most debilitating conditions associated with negative symptoms, lower quality of life and an increased risk for suicide. Despite current modalities of treatment, both medication-based and psychotherapeutic, many individuals don’t respond well, some experience worsening symptoms and others may turn to other substances to relieve their suffering. It is therefore imperative to continue research on CBD and the ECS to find specific molecular and neuro-pathway targets that respond and reduce symptoms of major depression and other neuropsychiatric conditions.
References
- Zarazua-Guzman, Sergio et al. 2024. An overview of major depression disorder: The endocannabinoid system as a potential target for therapy. Basic Clinical Pharmacology & Toxicology: 1-16.
- Sales, AJ, et al. 2018. Anti-depressant-like effect induced by cannabidiol is dependent on brain serotonin levels. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 86:255-261.
- Sales, AJ, et al. 2018. Cannabinoid induces rapid and sustained anti-depressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Molecular Neurobiology. 56(2):1070-1081.
- Beale, C. et al. 2018. Prolonged cannabidiol treatment effects on hippocampal subfield volumes in current cannabis users. Cannabis and Cannabinoid Research. 3(1):94-107.