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By Luke Sumpter Reviewed by: Carles Doménech

Depression is a widespread mental health condition that affects approximately 19.2 million adults within the United States. In Europe, approximately 4.6% of the population suffers from depression or anxiety[1]. In some people, depression can come and go. In others, the condition is a permanent companion that can significantly reduce one's quality of life. Depression draws billions of euros from the economy each year and robs individuals of their potential happiness. Conventional treatments for the condition include a range of medications that work in some cases, but are not exempt from side effects. Interestingly, some people who experience depression turn to cannabis. Researchers are certainly interested in the potential of the herb for an array of conditions, but could it help with depression?

WHAT IS DEPRESSION AND WHAT CAUSES IT?

We all get a little sad from time to time. Stress, anxiety, and emotional life events can leave us feeling down in the dumps. Eventually, this sadness lifts and enables us to continue living our lives undisturbed. But depression is more than sadness. It’s a chronic mental health condition that can linger for months or years on end. Sufferers aren't able to simply “snap out of it”.

POTENTIAL TRIGGERS FOR DEPRESSION

The cause(s) of depression is a complex subject. The condition can stem from a distressing life event such as the death of a loved one, a severe illness, or social/work disorders. For others, it might be the accumulation of minor events that sends them on a downward spiral. The risk of depression is enhanced if people take certain drugs and alcohol in an attempt to self-medicate.

In other cases, depression can come about for no apparent reason at all. Biological factors and personality type can play a role. One explanation for depression is a lack of neurotransmitters such as serotonin. Research has also discovered that the hippocampus—an area of the brain involved in learning and memory—is smaller in some depressed people[2]. This could be down to stress suppressing the production of new neurons.

COMMON SYMPTOMS OF DEPRESSION

Depression can manifest in many different ways. Sometimes the signs can be mild, and other times quite severe. Common symptoms of depression include:

• Continuous low mood or sadness
• Lack of motivation and apathy
• Low self-esteem
Insomnia
• Restlessness
• Difficulty concentrating
Overeating or appetite loss
• Persistent aches and pains
• Feelings of hopelessness
• Feeling tearful and crying often
• Feeling irritable and intolerant
• No enjoyment of life
• Suicidal thoughts

COMMON SYMPTOMS OF DEPRESSION

TREATMENT FOR DEPRESSION 

Multiple treatment options exist for depression. Each one is recommended individually based on the severity and specific characteristics of the condition.

Doctors may prescribe non-drug treatments for depression, suggesting things like psychotherapy and exercise to boost mood. Interestingly, aerobic exercise may increase endogenous cannabinoids that are responsible, together with other substances, for the so-called “runner’s high”[3]. Many depressed individuals can also benefit from cognitive behavioural therapy (CBT) to change patterns of thought and behaviour.

Doctors can also prescribe antidepressants in other cases. There are over 30 different types of antidepressants available, including selective serotonin reuptake inhibitors (SSRIs).

SSRIs increase levels of the neurotransmitter serotonin. They limit the reabsorption of serotonin into the presynaptic neuron, making more of the substance available. These medications are effective at stabilising mood in some patients, however, sometimes they are associated with side effects including nausea, nervousness, dizziness, sexual problems, weight gain, and insomnia.

These options help some people deal with and even overcome depression. In others, they fail to offer relief. Today, some people are exploring other options, including cannabis.

CANNABIS, DEPRESSION, AND THE ENDOCANNABINOID SYSTEM

If you smoke weed, you’re probably familiar with how it can make you feel. There are times when hitting a bong can initiate a fit of giggles. Some strains induce a heady buzz that lasts for hours, while others are more gentle and better suited to the serenity of the evening. However, there’s probably been other times when smoking weed has caused you to experience feelings of anxiety or even panic.

Because cannabis can have very different effects on people, it’s not guaranteed to improve a person’s mood.

Research is still exploring the effect of cannabis on depression. Before we delve into the studies, it’s important to make a few distinctions. As different strains contain different concentrations of cannabinoids and terpenes, they can have vastly different effects on mood.

To make things more complicated, different strains have wildly fluctuating levels of these chemicals. Some varieties are high in the psychotropic cannabinoid THC, whereas others are high in the non-psychotropic cannabinoid CBD. Furthermore, there are over 100 cannabinoids and 100 terpenes that produce their own effects. Therefore, “Does cannabis impact depression?” can be regarded as a poor and inadequate question. It’s more a case of discovering the impact of individual molecules and how they work together.

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WHAT THE RESEARCH SAYS

Unfortunately, comprehensive research in this area is lacking. So far, we have a shallow idea of these complex mechanisms. However, science has developed a greater understanding of how THC and CBD individually might affect mood.

When looking at the effects of these chemicals on the brain, it’s helpful to have an understanding of the endocannabinoid system (ECS). “Endo” means within, and “cannabinoid” is in reference to cannabis. This is referring to a cellular system involving biochemical processes that influence receptors in a similar way as cannabis. ECS receptors are found on numerous cell types throughout the body. So far, science has confirmed two main receptors—CB1 and CB2.

The ECS is also made up of specialized neurotransmitters that bind to these receptor sites and modulate the system. These molecules are known as endocannabinoids, namely anandamide and 2-arachidonoylglycerol (2-AG). As it happens, molecules from the cannabis plant can influence the same receptors thanks to their similar shape. Cannabinoids from cannabis—and other plant species—are known as phytocannabinoids.

Both anandamide and 2-AG play a key role in the dopaminergic system, and therefore in possible mood regulation[4]. Both of these molecules bind to CB1 nervous system receptors, and are also able to modify dopamine levels or their receptor activity[5].

THC (tetrahydrocannabinol) is one of the main constituents of modern cannabis cultivars. The molecule produces psychotropic effects by binding to CB1 receptors in the central nervous system. The cannabinoid may affect mood in the short-term by increasing dopaminergic cell firing.[6]

Research published in the _Journal of Affective Disorders_ investigated the effect of cannabis on depression, anxiety, and stress.[7] Researchers gathered data from the app Strainprint to examine the effects of certain strains.

THC isn’t the only cannabinoid they studied; CBD was administered as well. The study found that strains high in CBD and low in THC were associated with the largest changes in mood ratings. In contrast, strains high in THC and low in CBD seemed to promote relaxation.

This could potentially be due to CBD’s interaction with serotonin,[8] a neurotransmitter that regulates mood. CBD is believed to bind to the 5-HT1A serotonin receptor.[9]

CBD’s interaction with CB1 receptors doesn’t create the same powerful reaction, and therefore doesn’t affect dopaminergic neurons in the same way as THC[10]. Instead, CBD is suspected to be an antagonist or inverse agonist of CB1; while at the same time, it could also be an indirect agonist of this receptor. This ultimately suggests that CBD could increase anandamide levels by inhibiting an enzyme that breaks down the endocannabinoid. Increased levels of anandamide then bind to CB1 receptors and could produce their own effects on mood.

WHAT THE RESEARCH SAYS

The research regarding some cannabis molecules and depression is promising. However, comprehensive studies on the plant’s application for this condition are needed.

CANNABIS AND DEPRESSION: A COMPLEX RELATIONSHIP

Although acute exposure to THC can boost dopamine release, chronic exposure may blunt the dopaminergic system.[11] Long-term cannabis use may decrease the brain's response to dopamine and possibly lead to reduced feelings of reward and motivation.

As stated, cannabis isn't just THC. CBD is being studied for its effects on mood as well. Plus, researchers have yet to study over 100 other cannabinoids, terpenes, and other molecules in this domain. 

Hence, as the relationship with cannabis and depression is still unclear, the most sensible course of action is to discuss the matter with a healthcare professional.

External Resources:
  1. Depression and Other Common Mental Disorders https://apps.who.int
  2. Late-Life Depression, Hippocampal Volumes, and Hypothalamic-Pituitary-Adrenal Axis Regulation https://pubmed.ncbi.nlm.nih.gov
  3. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’ | Journal of Experimental Biology https://jeb.biologists.org
  4. The mesolimbic dopamine reward circuit in depression https://pubmed.ncbi.nlm.nih.gov
  5. Reversal of dopamine D(2) receptor responses by an anandamide transport inhibitor https://pubmed.ncbi.nlm.nih.gov
  6. The effects of Δ 9 -tetrahydrocannabinol on the dopamine system | Nature https://www.nature.com
  7. A naturalistic examination of the perceived effects of cannabis on negative affect - ScienceDirect https://www.sciencedirect.com
  8. Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. - PubMed - NCBI https://www.ncbi.nlm.nih.gov
  9. Agonistic Properties of Cannabidiol at 5-HT1a Receptors | SpringerLink https://link.springer.com
  10. Cannabinoids and Cannabinoid Receptors: The Story so Far https://www.cell.com
  11. The effects of Δ 9 -tetrahydrocannabinol on the dopamine system | Nature https://www.nature.com
Disclaimer:
This content is for educational purposes only. The information provided is derived from research gathered from external sources.