The World Health Organization (WHO) estimates that depression affected more than 300 million people across the globe in 2015, equating to more than 4% of the total worldwide population. Though those numbers could very well be much higher due to various factors such as the stigma surrounding the illness that may prevent someone from reporting their condition and the many cases that likely go unnoticed and undiagnosed. This can be particularly troubling considering that the number of people living with depression rose by 18.4% in the decade between 2005 and 2015. The WHO now ranks depression as the single largest contributor to disability worldwide.
With this mental illness affecting the lives of more and more people around the world, methods to counteract its debilitating effects become increasingly imperative. In recent years, cannabidiol (CBD) has entered into the mainstream discussion of potential treatments for depression, despite there being a shortage of research (at least in comparison to other more prominent antidepressants) into how the compound affects the human brain.
This article will seek to break down some of the ways CBD affects the brain—according to current research—and take a look at how it might be used to help with the effects of depression.
What is Depression?
Depression is generally characterized by a combination of factors, including sadness, emptiness, lack of pleasure or interest (even in activities one might have previously enjoyed), trouble sleeping, loss of appetite, tiredness and lack of energy, difficulty concentrating, and feelings of guilt and low self-worth. Depression can be long-lasting or recurrent and clusters of these symptoms can lead to extreme difficulty when it comes to basic functioning at work, school, home, and just everyday life. Extreme cases of depression can potentially lead to suicide, which accounts for more than 800,000 deaths a year.
Depressive disorders can generally be broken down into two main sub-categories:
- Major depressive disorder/depressive episodes: This form includes symptoms like loss of enjoyment and interest in much of anything, depressed mood, and decreased energy, with episodes categorized as mild, moderate, or severe.
- Dysthymia: This form includes similar symptoms, though they tend to be longer lasting and less severe, and may be chronic or persistent.
What are the Causes of Depression?
There are a wide variety of factors that can influence whether or not a person experiences depression and how severe that experience might be, including:
- Stressful life events
- Genetic vulnerability
- Physical illness
- Physical pain
- Chronic stress
- Social isolation
- Faulty mood regulation in the brain
- Other emotional disorders
This vast array of possible causes and influences is one of the main factors that makes depression such a complex illness that affects many people in a myriad of ways—thus necessitating different treatments for different individuals.
What is CBD?
Though there are more than 550 chemical compounds and more than 100 phytocannabinoids in cannabis, CBD is one of the two main active components in the plant. The other primary component, tetrahydrocannabinol (THC), has traditionally garnered most of the attention of the public due to its psychoactive effects. Recently, however, questions around the uses and potential health benefits of CBD has thrust the compound into the discussion spotlight.
How Can CBD Help With Depression?
Though CBD has yet to be definitely proven to treat depression, a number of studies within the past two decades point to some potentially antidepressant-like effects of the compound, by:
- boosting your endocannabinoid levels, specifically the “bliss” molecule anandamide—and a deficiency of endocannabinoids has been linked with higher levels of depression.
- reducing the effects of anhedonia.
- significantly enhancing the levels of serotonin in the brain, producing an antidepressant-like effect.
- promoting neurogenesis in the hippocampus, which has been linked to recent research into effectively combating depression.
- increasing brain-derived neurotrophic factor (BDNF) levels, thus helping brain neurons to survive and promoting the growth of new neurons and connections.
- reducing inflammation and pain, one of the major causes of depression.
What is the Endocannabinoid System and How Does it Relate to Depression?
Though a relatively newer area of study for science—wherein most of the relevant studies have been conducted over the last two decades, partly triggered by cannabis research—this system of neurotransmitters can play a significant role in our body’s ability to regulate homeostasis and overall health.
Endocannabinoids (eCB) function as the messengers of the endocannabinoid system (ECS), much like how dopamine and serotonin are the messengers of the nervous system. The two primary endocannabinoids in your system are anandamide and 2-ArachidonoylGlycerol (2-AG). The former’s name derives from the Sanskrit for “bliss” and is involved with memory, appetite, and pregnancy—and it has also been identified as the source of the “runner’s high” felt during or after intense exercise. The latter has been linked to cardiovascular health, emotional states, and protection from seizures, as well as being connected to the contented feeling one experiences after orgasms.
Endocannabinoid receptors sit on cell surfaces, waiting for these eCBs to bind to them, which in turn affects mood, sensation, immunity, and consciousness. Different cell types have different receptors that are sensitive to different eCBs. The two primary receptors for the ECS are CB1 and CB2.
- CB1: These are some of the most common receptors in the nervous system and are critical to the healthy functioning of the brain. They can moderate one’s mood, memory, motor function, or one’s perception of pain, depending on where they are located in the brain. CB1 receptors are also responsible for the psychoactive properties created when THC binds to them.
- CB2: Mostly found in the immune system, these help moderate inflammation and our immune response to pathogens.
Though most cannabinoids bind to both types of receptors, CBD does not directly trigger either receptor. Instead, it binds to receptors in a different spot than where other cannabinoids typically do, leaving the normal binding site free. In the process of this atypical binding, however, CBD modifies that receptor’s ability to bind to cannabinoids, in a process referred to as allosteric modulation. This modification effectively makes it harder for the CB1 receptor to activate or over-activate.
While this might seem like an undesirable side effect, many negative complications with the ECS arise from an overactive system. Especially if one is experiencing an overabundance of stress and anxiety, part of the reason for this might be due to overstimulation of cannabinoid receptors.
How Does CBD Affect Enzymes in Your Body?
Endocannabinoids are neurotransmitters synthesized from fats by different enzymes. When your body gets the signal to synthesize more of these eCBs, these enzymes are activated. (This is part of why omega-3s and other essential fatty acids are so important, because they help boost production of eCBs.)
Once anandamide and 2-AG have effectively delivered their messages, however, the body then seeks to prevent them from continuing to stimulate the ECS indefinitely. Two of the most important enzymes that factor into this process are FAAH and MAGL. The former breaks down anandamide, while the latter breaks down 2-AG. Since CBD can potentially inhibit these enzymes, it can lead to increased levels of eCBs, specifically anandamide and 2-AG. Higher levels of anandamide can promote relaxation and “feel-good” feelings, while higher levels of 2-AG can reduce your perception of pain and also further activate your memory.
This process of elevated levels of neurotransmitters is called reuptake inhibition and is reflected in the core function of selective serotonin reuptake inhibitors (SSRIs), which are some of the most common drugs prescribed for depression and anxiety.
How Does CBD Affect Serotonin Levels?
Much like serotonin, CBD can bind to and activate the body’s 5-HT1A serotonin receptors. In a study of rats subjected to the forced swim test (FST), CBD reduced immobility time in a manner similar to the antidepressant imipramine. This indicates that CBD could potentially have a prohedonic effect similar to that of other antidepressants.
Similarly, another study noted that the administration of CBD significantly enhanced serotonin levels, creating an antidepressant-like effect in the rodents tested.
Additionally, the anti-anxiety drug buspirone also activates these same HT1A receptors and has been shown to increase neurogenesis in the hippocampus. Thus, CBD could potentially have a similar effect.
What Is Neurogenesis and How Does it Relate to Depression?
Much of the research in recent years relating to the causes and effects of depression have centered around the study of the hippocampus and its role in learning, memory, and emotion. Scientists have been researching the neural plasticity of the brain and studying how this particular region of the brain can atrophy and shrink, but they have also been looking into its capability of neural regeneration, or neurogenesis. In fact, a large part of why antidepressant medications can be effective for many people is due to their ability to oppose neural atrophy and degeneration, while also helping form new neurons and connections.
CBD factors into this thanks to its potential ability to protect neurons in the hippocampus from degeneration in both rodents and humans. Some studies have also linked this boon to neurogenesis as a potentially useful treatment for epilepsy—in fact, the anti-epileptic drug Epidiolex is currently the only CBD product approved by the FDA.
Along with its aforementioned potential to increase the body’s level of endocannabinoids—which can stimulate neuron growth and help induce more positive emotions thanks to anandamide—CBD may potentially also increase brain-derived neurotrophic factor (BDNF) levels. This protein helps neurons in the brain survive, while also encouraging the growth of new neurons and connections. Not all studies corroborate this link between CBD and rising BDNF levels, however, so more research is needed to fully confirm how the relationship between the two functions.
Can CBD Help With Pain Management?
Though many studies focused on the connection between cannabinoids and pain relief concern more than just CBD and occasionally find mixed results, some have been able to at least partially substantiate claims that the compound can be used for reducing pain and inflammation.
One such study from 2012 found that CBD (as well as other cannabinoids) can indeed help reduce inflammation and neuropathic pain, without causing major psychoactive side effects or significantly altering analgesic tolerance. Similarly, a 2016 study determined that even topical CBD application can provide potential relief of pain and inflammation associated with arthritis without evident side effects.
Given how large of a role pain can play in one’s experience of depression, the potential relief of some of that physical pain might help those with the mental illness reduce its debilitating effects.
What Are the Side Effects of CBD?
Though a recent 2017 study confirmed the “favorable safety profile” of CBD, it nevertheless concluded that common side effects include tiredness, diarrhea, and changes to one’s appetite and/or weight. When compared with other drugs used to treat epilepsy and psychotic disorders, however, these side effects were judged to be on the lower end of the spectrum—thus potentially leading to better compliance and adherence within patients.
Much like most of the scientists that conducted other studies concerning how CBD affects the body, however, the authors of the above trial noted that much more research is still necessary to be more confident about the potentially wide-ranging effects of this compound.
It’s also important to note that most CBD consumer products on the market are not regulated and may have different CBD (and THC) levels than advertised. Coupled with the lack of information about appropriate dosing—especially at the individual level—knowing which CBD product to use and how much of it to apply can be extremely difficult.
Can CBD Make Depression Worse?
Though some studies have indicated that chronic use of THC-containing cannabis can temporarily alleviate symptoms of depression for a short time but potentially exacerbate them in the long run, it does not appear that any concrete studies on the long-term effects of exclusively using CBD for depression in humans have been conducted.
How Does CBD Interact With Other Medications?
CBD can inhibit the activity of a family of liver enzymes known as cytochrome p450 (also known as CYP enzymes). This particular enzyme group helps metabolize 60–80 percent of marketed medications. If these enzymes are inhibited, how our body metabolizes various compounds can be significantly altered. This is especially true for people taking certain medications to combat cancer and epilepsy.
Different studies conducted only a few years later, however, indicated that CBD might also be responsible for inducing those same p450 enzymes, rather than inhibiting them. This points to the necessity for more research in the area, but nevertheless means that those taking CBD along with medications that rely on p450 for metabolization may need to alter their dosage of the latter depending on how the CBD affects their body.
Moreover, it’s likely not a good idea to stop taking your prescription medications in favor of CBD without consulting your doctor or other medical professional.
A Final Word on Anecdotal Evidence and the Limitations of Using Animal Trials to Study Depression
In addition to clinical trials, anecdotal evidence may also suggest that CBD can be effective either in conjunction or in place of traditional antidepressant treatments. A survey of 2,400 HelloMD community members, for instance, found that 80% of those polled found CBD to be extremely effective at treating their illness and 42% stopped using traditional medicines in favor of using CBD. Though the sample size is quite small and localized within a specialized community, the study nevertheless points to the prevalence of CBD being used by many people as one means of treating depression.
It’s important to keep in mind, however, that research into the ability of CBD to provide some relief for those with depression remains fairly limited due to the fact that many of the clinical trials looking into the compound’s potential antidepressant qualities are conducted on non-human subjects, specifically rodents.
While this may give researchers clues into how a substance like CBD might affect the human body, a mental illness like depression is so incredibly complicated and idiosyncratic to each person who experiences it—with a myriad of often unmeasurable factors affecting that experience in countless ways—that it’s difficult to truly know how the compound might affect a single person’s condition, let alone the greater public at large. Even with extensively tested antidepressants, researchers continue to find out new information about how they affect the human body, not to mention certain individuals.
So it’s important to take any information about CBD’s potentiality as an antidepressant with a grain of salt, at least until many more studies on its effects are completed—and those results duplicated in further studies.
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