Relationship between the endocannabinoid system and depression or anxiety
The increasing acceptance of cannabis use for medical and recreational purposes by consumers around the world has also raised the interest of the scientific community in its therapeutic potential. The effects and benefits of cannabis use for the treatment of physical pain are well known and its effectiveness in the treatment of mental disorders is increasingly being studied, with depression and anxiety being the focus of these studies. All over the world, people of different ages, ethnicities and social classes are affected by depression. The severity of depression can range from increasing an individual’s isolation to serious disturbances in people’s daily lives. The disease is difficult to diagnose as the symptoms are difficult to measure and there are many different subtypes of disorders. Statistics show that women are generally twice as likely to suffer from depression as men, and that about 20% of the world’s population suffer from the disease at some point in their lives. The recurrence of depression after recovery can also put you at risk of developing other heart disease or other psychiatric disorders. Despite the broad severity of these disorders, antidepressants are prescribed to treat practically every case and type. However, antidepressants are not always effective treatments, which underlines the need to explore alternative treatments for these conditions. Both anxiety and depression have been associated with increases in unproductivity, drug abuse and even higher mortality rates, often influenced by the lack of individual treatment beyond a family doctor. Depression has a projected heredity of sixty percent, so genetics probably plays a role in the development of these diseases. Given the difficulty of controlling all risk factors for depression, most research has focused on understanding the biological pathways involved in patients for potential treatment. The prevailing biological theory for depression and other affective disorders is the monoamine hypothesis. Monoamines, including serotonin and dopamine, stimulate G protein-bound receptors on postsynaptic neurons to respond to neurotransmitters responsible for influencing brain reactivity. Pharmacologically, the monoamine hypothesis was supported. In the treatment of anxiety, SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) are the most commonly administered classes of drugs. The effectiveness of SNRIs varies greatly from case to case, and treatment with SNRIs can even worsen physiological symptoms. The endocannabinoid system has shown that it may be a new target for the development of a much needed therapeutic alternative. To better understand the novelty of the use of endocannabinoids as antidepressants, it is important to distinguish between exogenous cannabinoids, phytocannabinoids and endogenous cannabinoids (endocannabinoids). Exogenous cannabinoids refer to all cannabinoid compounds that arise outside the human body and include those that are pharmaceutically manufactured or derived from plants (phytocannabinoids). In contrast, endocannabinoids refer to cannabinoid compounds that originate only from the human body. To know exactly what the relationship is between the endocannabinoid system and depression and anxiety, we need to know that the human endocannabinoid system consists of two main subtypes of cannabinoid receptors (CB1 and CB2). CB1 receptors are the most common subtype and focus on the central nervous system, especially the limbic system and the areas of the brain associated with emotions. CB2 receptors are mainly found in the peripheral tissues of the immune system, but it has also been discovered that they are found in the cerebellum and hippocampus. Both receptor subtypes belong to the same class of G protein-coupled receptors that regulate neurotransmitter release when stimulated. The location of these receptor subtypes and their mechanism of action, which involves the inhibition of neurotransmitters, has led to speculation that they might be involved in the treatment of depression. There has also been more direct biological evidence that these receptor subtypes may also be involved in the development of depression. Studies have shown that genetic polymorphisms of CB1 and CB2 receptors have been linked to depression and even resistance to treatment in some patients with depression. Although cannabis was primarily restricted to a recovery context because of the stigma involved, studies in behavioural mice showed that their coping mechanisms for anxiety and stress included upregulation of their endocannabinoid system. This biological evidence of a disruption of the endocannabinoid system in patients with depression and the behavioural evidence that the endocannabinoid system is involved in the extinction of stress confirms the investigation of whether endocannabinoids and exogenous cannabinoid ligands can act as effective antidepressants. As the stigma associated with the use of marijuana for medical purposes has decreased dramatically in recent years, research worldwide has focused on investigating the use of endocannabinoids and exogenous synthetic cannabinoids to treat conditions ranging from diseases such as Alzheimer’s to cancer. Since it has been established that the CB1 and CB2 receptor subtypes of the endocannabinoid system play a role in areas of the central nervous system associated with emotions, many other research studies have focused on understanding the role of these receptors in reducing or treating depression and anxiety. Because most research studies focus on assessing synthetic CB1 receptors for antidepressant effects, researchers from the University of Mississippi focused their 2010 study on elucidating the role of phytocannabinoids like delta-9-THC. Delta-8-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN) and cannabichromes (CBC), which are most common in the types of cannabis ingested by recreational users. In this study, these phytocannabinoids were extracted from strong cannabis sativa and tested in combination with desipramine and fluoxetine hydrochloride for comparison with TCAs and SSRIs. In addition, an important conclusion from this study is that CBD, the non-psychoactive component of cannabis, concludes that despite major and very significant advances in the last decade in the field of cannabinoid receptors and the treatment of depression or anxiety, there are still many unknowns and scientific gaps that could possibly be translated into viable human treatments in the near future. Perhaps sooner than we think, patients with severe mental disorders who do not respond to classic antidepressants could benefit from research into possible applications of the endocannabinoid system.