Depression is defined as “A mental condition characterized by feelings of severe despondency and dejection, typically also with feelings of inadequacy and guilt, often accompanied by lack of energy and disturbance of appetite and sleep” (Oxford Dictionary, n.d.). According to the World Health Organization (healthline, n.d.), 350 million people suffer from depression worldwide, that being 5% of the worlds population, at any given time. This shows that depression is a common and severe issue that is impacts many people, and finding a solution to the illness is greatly demanded. Antidepressants have been around since the 1950’s (Alamo and López-Muñoz, 2009), and have had varied success since then. Recent research into the medicinal benefits of cannabis has seen the rise of cannabis being used to treat depressive episodes in individuals.
Cannabis is a drug that is made from the dried leaves and flowers of the hemp plant Cannabis sativa. It consists of two main chemical components. The first is tetrahydrocannabinol, known more commonly as THC, which gives the plant its psychoactive effects. The second is Cannabidiol, known as CBD. It has grown naturally in the wild for centuries.
The topic of using cannabis as a form of medicine is one that is discussed frequently around the world in today’s society. Due to legal implications due to the prior illegality of the substance, studies into the positive and negative effects of its use on physical and mental health are only now appearing. While cannabis products are more frequently used for pain management, there are a growing number of studies that suggest that cannabis could help patients suffering from mental illnesses, more specifically depression.
When researching this topic, I found interesting the supposedly contradicting opinions and studies surrounding whether cannabis actually benefitted mental health in any way, more specifically whether it helped those suffering from depression.
With a topic so relevant in today’s society, I was curious as to how different compounds of cannabis might interact with the brain, to see if it was only specific compounds that could have an antidepressant-like effect or if they all have an impact in some. This lead me to come up with the research question, “To what extent can research into the positive and negative effects of cannabis use help us to develop more effective cannabis based interventions for depression?”
This essay will aim to provide an argument for why cannabis could be used effectively by patients to treat depressive disorders. It will also look at whether cannabis could be used instead of or alongside current antidepressants that are prescribed to patients, in order to determine whether cannabis is more effective than other medications that are available. To do this, the essay will firstly consider the biological basis for depression, in order to then be able to understand how components of cannabis could counteract these biological changes. Next, it will consider how the two main chemical components of cannabis, THC and CBD could be useful in treating depression individually. Finally, an evaluation of qualitative data will be examined to determine whether the biological basis for using cannabis as an antidepressant actually seems to have an positive impact on patients.
The application of the findings of this essay, if it is shown that cannabis can be used as an effective treatment for depression, would suggest that the medicinal uses of cannabis should be looked into more and that cannabis should possibly be prescribed to patients as an antidepressant, possibly also leading to the legalisation of cannabis for medicinal use.
Sources used will be from research papers and books. This way information will only come from credible sources, as information wont be used from websites.
Understanding the Biological causes of Depression
Understanding the biological causes of depression is relevant before examining the effects of cannabis, as many of these effects have a biological basis to them. Therefore, understanding how depression alters processes in the brain can help to understand how the effects of cannabis might counteract these changes.
The monoamine theory of depression suggests that depression is a result of imbalances of chemicals in the brain (Nemade, n.d.), more specifically a depletion of the neurotransmitters serotonin, dopamine and norepinephrine in the central nervous system. These neurotransmitters and their receptors are what certain types of antidepressant medications aim to alter.
Changes in levels of these neurotransmitters have an effect on us both physically and psychologically. Serotonin is involved in various processes such as sleep, mood, and hunger. When these are altered due to a decrease in serotonin production, it can cause depressive symptoms such as loss of appetite or low mood to manifest.
Secondly the effects of changes to levels of norepinephrine are to be considered. When looking at the effects of the neurotransmitter norepinephrine in the 1960’s, the catecholamine hypothesis was created as a hypothesis for the cause of depression. It suggested that depression is caused by specifically because of a lack of the neurotransmitter norepinephrine. Autopsy’s performed on people who had suffered from multiple depressive episodes did support this theory as they had significantly less norepinephrinergic neurons in the brain. However, other studies have shown that a decrease in serotonin production also triggers a drop in norepinephrine, which in turn leads to depression, so serotonin clearly plays a key role in the onset of depression.
Lastly, dopamine is said to influence the development of depression also. Dopamine causes us to have a drive towards a goal, and gives us a sense of pleasure during tasks, and so a lack of dopamine can result in a lack of motivation and drive, which are both symptoms of depression.
With the knowledge of how these imbalances of neurotransmitters in the brain are suggested to cause depression in humans, it is now able to be understood how cannabis may be used as an effective treatment for depression.
The Effects of tetrahydrocannabinol (THC) on dopamine
THC, short for tetrahydrocannabinol, is one of the main chemical components of the cannabis plant, and is what gives cannabis its psychoactive effects. The fact that it is a key component of cannabis means that understanding how THC interacts with the levels of neurotransmitters in the brain is an important aspect to consider when discovering if cannabis is an effective treatment method for depression.
In cannabis, the euphoric, relaxed and happy sensation felt while ‘high’ is almost entirely due to the THC components interaction with a type of receptor called cannabinoid receptors that are found almost everywhere in our brain and are part of the endocannabinoid system (Ashton and Moore, 2001). The effects of cannabinoids such as CBD are controlled and mediated by the cannabinoid receptors, specifically the CB1 and CB2 receptors. CB1 receptors appear in high quantities in several parts of the brain and mainly mediate the psychoactive effects of cannabinoids.
These cannabinoid receptors are bonded by a molecule called anandamide, which is known for regulating mood, as well as other functions. This molecule’s interaction with multiple intracellular enzymes in short actually reduces the amount of neurotransmitters released, so actually decreasing the levels of serotonin and dopamine in the system. This can greatly reduce the activity of the brains neural networks. This would possibly result in the worsening of symptoms of depression instead of treating them. To understand why this is, consider some of the physical symptoms of clinical depression as described by the NHS (no date).
• Moving or speaking more slowly than usual
• Changes in appetite or weight
• Lack of energy
When looking at these symptoms, the reduced levels of neurotransmitters can cause these symptoms above, as a lack of dopamine causes a lack of energy and a lack of serotonin results in the other two symptoms mentioned. Although these are only short-term effects, using cannabis as a form of treatment could likely cause an increase in severity of symptoms in sufferers of depression, possibly worsening the condition.
However, the THC does cause something else to happen in the brain. Substances that trigger dependencies, including cannabis, have been found to all trigger an increase in dopamine production. This suggests that more dopamine is released than is inhibited due to THC. The main source of dopamine in the brain, the dopaminergic neurons, are one of the few places where there are no known CB1 receptors (cannabinoid receptors), so THC can’t directly impact these neurons. However, the release of dopamine from these neurons is usually prohibited by GABAergic neurons which do have CB1 receptors. When THC interacts with these CB1 receptors connected to the GABAergic neurons, as mentioned above, it reduces the amount of signalling from the GABAergic neurons, and therefore the release of dopamine is no longer prohibited. This results in the increase of levels of dopamine in the body (Dubuc, no date).
In a paper by David J Diehl (1992), he discussed the findings that decreased dopamine activity is linked to depression in humans, as explained on page 7. Therefore, the increase in dopamine production caused by the cannabis and more specifically the THC may in fact be beneficial to sufferers of depression, if the adverse physical reactions of decreased levels of serotonin and other neurotransmitters can be tolerated.
However, this study is more correlational than causational as it only observes that depressed patients have lower levels of dopamine. If the depression is causing the lower dopamine levels, then even if the levels are brought up, they may just get reduced again because of the depression, and therefore cannabis would not be an effective treatment for depression in this regard. However, if the dopamine levels are causing depression, then cannabis may indeed be a rather effective treatment for depression.
The Effects of Cannabidiol (CBD) on serotonin
While THC is an influencer in the levels of the neurotransmitter dopamine, the other main component of cannabis, called Cannabidiol (CBD) has an effect on the production of serotonin. Cannabidiol is the non-psychoactive component of cannabis. Unlike THC, CBD has little binding effect on the cannabinoid receptors CB1 and CB2 (Mackie, 2008). It does however activate multiple non-cannabinoid receptors and ion channels. At high concentrations it directly activates the 5-HT1A receptors. This is important because the 5-HT1A (hydroxytryptamine) receptor is a subtype of serotonin receptor found in the presynaptic and postsynaptic regions of the brain, regions that are known to control mood, cognition and memory. The role of 5-HT1A receptors in depression has been supported in various research papers such as Samuels et al (2017). A type of antidepressant medication currently prescribed to patients are reuptake inhibitors, for example selective serotonin reuptake inhibitors (SSRI’s) such as Prozac and Zoloft, which target 5-HT1A receptors in the same way as CBD does. It works by stopping neurotransmitters from being reabsorbed into the nerve cells, and so keeping the levels of these neurotransmitters, such as serotonin and dopamine, high. The fact that CBD has the same effect on these 5-HT1A receptors as current antidepressant medications shows that CBD could be effectively used to treat depression in patients for which the reuptake inhibitor antidepressant medication is also effective. However, in patients where this type of medication does not work for them, using CBD or cannabis in this way may not have any impact on them at all and so may prove ineffective.
To support the fact that CBD could be effectively used as an antidepressant, a study done by Zanelati et al (2009) tested the hypothesis that CBD would have an antidepressant effect on mice. This was tested by either injecting the mice with CBD, an antidepressant drug or a control condition. After this they were subjected to the forced water test, in which the mice are put individually into glass cylinders containing water. This test is commonly used to test the effectiveness of anti-depressant medication, as it looks at the time it takes for the mice to change from active behaviours, such as struggling and swimming, to passive coping strategies such as immobility in this inescapable situation, i.e. it looks at the time it takes for the mice to give up on finding a way out of the cylinder. Their level of immobility was measured for the last 4 minutes of the 6-minute period that they were in the cylinder for. When this test was done to test SSRI antidepressant medication, it was shown to postpone the time in which the mice transitioned from active to passive coping behaviours, therefore showing its effectiveness as an antidepressant. The results from this experiment where CBD was being tested showed similar results to that CBD had the same impact on the mice as the antidepressant, and so suggests it could be used as an effective treatment. A limitation of this study is that it was only conducted on mice, so the results may not truly reflect how humans would react to CBD. However, these mice are used specifically because their behaviours closely resemble human behaviours and so are relatively reliable in informing researchers how humans would react to a stimulus. Therefore, this research supports the argument that cannabis could be used effectively to treat depression, possibly as a substitute to current antidepressant medication.
Qualitative Studies
Having looked at how cannabis should biologically affect the brain, it would seem that cannabis use would have a positive impact on patients when being used to treat depression. But it is important to look at whether this is what is actually reported by those using cannabis to treat depression.
However, many studies seem to suggest that cannabis in fact has a negative effect on mental health, and that it can in fact increase chances of developing mental disorders such as depression. A 15-year follow-up of a community sample of 1920 participants in a study (Bovasso, G.B, 1980) appeared to show that those that used cannabis were 4x more likely to develop depression, as well as an increase in suicidal ideation, suggesting that cannabis has a negative effect long-term. However, in this study, the participants using cannabis were referred to as abusing the drug. This therefore suggests that the cannabis here was not being used in a regulated and medically sensible way and instead in a reckless way. This leaves doubt as to whether this is an accurate representation of what medical cannabis what actually do as a controlled dosage of cannabis may have shown different results on these participants.
A similar Australian study (Patton et al, 2002) also suggests that long-term cannabis use can cause an increased risk of developing mental illnesses. In this study the cannabis use of 1601 14-15 year olds from the Australian state of Victoria was recorded for seven years. This study suggested that there was a dose-effect relation between the use of cannabis and illnesses such as depression and anxiety, with those using cannabis more frequently showing higher rates of these mental illnesses. Those using cannabis at least once a week had approximately a twofold increase in risk for later developing depression. However, the disadvantage of studies similar to this is that they rely heavily on qualitative data. For a start these types of studies can’t be considered to be representative of the general population. This is because they both include only children from one particular area of the world so it can’t be said to represent all children. Also this research doesn’t establish a cause and effect relationship between cannabis use and depression, it only shows that there is a link between the two. The problem of social desirability might come into play here also, as cannabis is an illegal recreational drug and the participants desire to appear in a positive light may mean that they underestimate or ignore all together any cannabis use that did occur. Another issue when looking at the evidence for using cannabis to treat depression is that the majority of the participants for these studies are children. At a time when the brain is still developing, cannabis could possibly be more harmful to this age group than those that are older. The same effect can be seen when children use prescribed antidepressants such as Prozac (Kidsmentalhealth, no date). There are a small percentage for whom suicidal thoughts and depressive feelings are actually worsened instead of improved. This indicates that it may not be the cannabis specifically that causes a worsening in depression in children, but just a risk that all children taking this type of medication may have to incur, simply due to the fact that their brains are not yet fully developed. More research would have to be done into adults use of cannabis in order to see if the same results would occur, in which case cannabis may not be a safe antidepressant after all.
What’s limiting about these studies is that they show the possible consequences of long-term use, but the explanation as to why this happens is very limited as of yet. This means that it’s hard to say if there is any biological basis to the theory that it might increase risk of depression. They also only refer to those using cannabis for recreational purposes. So while they may give an idea of the consequences of long-term use, it doesn’t specifically refer to those using cannabis to treat depression. Therefore, when using cannabis for medicinal purposes, it may have a different effect.
A study that suggests that cannabis can in fact have a positive effect when being used to treat depression a study done by Denson and Earleywine (2006) that suggested that cannabis use does lead to decreased depression. Over 4400 adults completed an online survey, which looked at individuals who were suffering from depression and who consumed cannabis either every day, once a week or less, or never. The results showed that those who consumed cannabis daily or once a week or less reported less depressed mood and a more positive affect than non-users. The large sample size means that this study has high ecological validity, however the study does not specify whether the participants have actually been diagnosed with depression or whether they are simply self-diagnosing. This could lead to unreliable results as it’s not then guaranteed that the results show how cannabis helps those with clinical depression. However, the results are stil significant as it allowed depressed patients who would not have left their home to go to a test centre to still take part, and so arguably targets more severely depressed people due to it being an online survey.
Conclusion
My research question was “To what extent can research into the positive and negative effects of cannabis use help us to develop more effective cannabis based interventions for mental disorders?”. Through the course of this essay I have achieved a deeper understanding of the possible psychological effects caused by cannabis, both positive and negative, and the evidence suggests that cannabis could be used to effectively treat depression. In certain cases, this could be used alongside traditional medication, but for other patients this could be used instead of, for example CBD could be a substitute for SSRI medication. However, it should also be said that much of the biological research has been done primarily on animals, specifically mice, and not humans, and so while patients report that cannabis is effective for them, more research should be done to determine its physical short-term and long-term consequences.
Until more research is done into the long term consequences of cannabis, its difficult to say whether this would actually be an effective treatment method for mood disorders. Overall, the research seems to show that, when looking at the issue from a more biological perspective, in theory cannabis should be an effective treatment for multiple mental illnesses but specifically depression. However, some of the qualitative studies seem to suggest that this in fact has the opposite effect. Although, these studies that suggest that cannabis isn’t an effective treatment only look at those using it recreationally, not medicinally, so this may not truly reflect how patients suffering from depression may react to cannabis. However, this negative effect is especially suggested by the more long-term studies where it seems particularly worrying the number of people who have reported a long-term adverse effect. This may suggest that more research needs to be done on the long-term effects of cannabis on those already suffering from depressive episodes this might impact the ability of cannabis to be a long-term solution to depression. So while its long-term effectiveness may be relatively unknown as of yet, it is clear to see from the evidence shown throughout this essay that there are definitely benefits to mantal health and it wouldn’t be unrealistic to prescribe cannabis to patients to treat depression,, at least in the short-run.
When looking back at the research, it seems that the CBD component of cannabis is on the whole better at treating depression than the THC component. This is because, although the THC does cause more dopamine to be released, theoretically relieving the symptoms of depression, the THC, which causes the psychoactive effects, results in multiple undesirable side effects that are too closely linked to the symptoms of depression, and so could possibly create more distress to patients instead of easing symptoms. However, it is currently possible to isolate the CBD component of the cannabis plant to create pure CBD oil. This is legal in the UK when being prescribed to patients with seizures. Given the fact that CBD has been seen to act in the same way and to the same degree as current antidepressants available, it would seem that looking into this CBD oil for use as an antidepressant would be beneficial and could work as an effective treatment for depression. Also, considering declassification of cannabis as an illegal substance would allow the science community to study the clinical benefits of this plant in greater detail, as it is ever increasingly apparent that it has the potential to have major benefits for not only treating depression, but a wide range of illnesses.