Introduction

The cannabis plant is known to produce specific chemicals (cannabinoids), most notably cannabidiol (CBD) and tetrahydrocannabinol (THC). These alter the way the brain functions, leading to the use of cannabis as a recreational drug. In recent years, however, the medical use of THC has been studied as a treatment for depression.¹

Depression is a mental health condition which is characterised by feelings of sadness and a lack of interest in activities. People with depression may also experience sleep disturbances, changes in appetite, and can find it harder to manage their daily routine.²

Mood regulation serves as a way in which we can try to control our emotional state through changing the way we think about the world. Someone who tends to make negative inferences about life can be more prone to depression.³ This article will explore the effectiveness of THC as a mood regulator and its application in alleviating depression.

Understanding THC and its effects on the brain

How THC works

Cells of the brain and central nervous system have cannabinoid receptors (CB1 and CB2) which, when stimulated by chemicals like THC or CBD, release signalling molecules called neurotransmitters. These have various functions:

• Acetylcholine and noradrenaline: involved in attention, cognition and muscle movement
• Dopamine, which activates the ‘reward centre’ in the brain

Endocannabinoid system and mood regulation

Cannabinoid receptors work alongside molecules called ligands, making up the endocannabinoid system (ECS). Through neurotransmitters, this system controls the developing central nervous system and influences our physiological and cognitive processes.⁴ 

When this system is disrupted, the signalling of serotonin and dopamine – so-called happy hormones – are reduced. This has been demonstrated in both depressed animals and patients.⁵

THC is able to trigger the release of dopamine in the short-term, helping to reduce symptoms of depression. However, using THC over a long period of time can actually dampen this effect.⁶

Depression and mood dysregulation

Symptoms and causes of depression

Depression can manifest with symptoms such as:

• Loss of energy
• Sleep changes (insomnia or excessive napping)
• Changes to appetite
• Feelings of worthlessness or hopelessness
• Suicidal thoughts

Biological, cognitive and environmental factors can contribute to the onset of depression. One theory of depression focuses on serotonin imbalance, meaning people with a deficiency in this neurotransmitter may be more prone to low mood.⁷

Cognitive theories focus on the idea that people with depression think differently to those without it, with emphasis on a negative worldview.⁸

People may also develop depression in response to their childhood experiences.

Multiple theories can be used to explain why some individuals are more (or less) susceptible to developing this mental health disorder.

Challenges in mood regulation for depressed individuals

People with depression experience difficulties in sustaining a positive emotional state, due to negative biases in the way they perceive themselves. They may focus more on their own assumed flaws, and they may also believe others see them the same way. This makes these individuals more susceptible to stress and dejected emotions.⁹

Potential positive effects of THC on mood regulation in depression

THC, or cannabis use in general, has been associated with mood disorders. However, it has paradoxically been investigated as a therapeutic. Some of the reputed benefits include:

• Reduction in anxiety, which is often diagnosed alongside depression
• Changes in the way negative stimuli are processed¹⁰
• Short-term improvements in mood e.g., feelings of relaxation and euphoria
• Improved motivation, due to stimulation of the brain’s reward system¹¹

Potential negative effects of THC on mood regulation in depression

The negative effects of THC can occur after short-term and long-term use, and include:

• Anxiety and increased risk of paranoia, especially in vulnerable individuals
• Attention, memory and motivation impairments which exacerbate depressive symptoms
• Addiction, as well as tolerance, reduce the positive effects of THC¹²

Evidence from studies on THC and depression

Research has demonstrated mixed findings on the effects of THC for depression and mood regulation. Cannabis use in general may be associated with depression.¹³,¹⁴

However, it appears that the dose of THC plays a role in how it affects the mind. A smaller dose can reduce negative emotional responses, but in larger amounts it becomes detrimental.¹⁵

Furthermore, even short-term use can cause adverse effects such as:

• Psychosis, or losing touch with reality through hallucinations and delusions
• Impaired coordination
• Anxiety
• Suicidal thoughts

Long-term effects can result in:

• Cannabinoid hyperemesis syndrome (CHS), characterised by severe nausea and vomiting
• Mood disorders or exacerbation of existing psychotic disorders
• Withdrawal syndrome
• Cardiovascular and respiratory disease¹⁶

Limitations and gaps in research

THC content in cannabis and individual responses can vary widely. Every individual has a unique genetic makeup which can interfere with the way THC interacts inside your body. 

Furthermore, there is a paucity of large-scale, long-term studies on THC and depression. This means that the effects of THC in the long-run are poorly understood. It is also difficult to extrapolate the findings from smaller studies of people to the general population.

THC in comparison to other treatments for mood regulation in depression

Comparison to traditional antidepressants

Antidepressant drugs work by restoring normal levels of serotonin and noradrenaline. Selective serotonin reuptake inhibitors (SSRIs) make it easier to regulate emotions, sleep and appetite.¹⁷ These generally have fewer side-effects, leading to their widespread use as medication for depression. Examples of antidepressants include:

• Citalopram
• Escitalopram
• Fluoxetine
• Paroxetine
• Sertraline

Compared to THC, which temporarily alleviates depressive symptoms, SSRIs are designed to help regulate serotonin levels over an extended period of time. Used together, they might cause adverse effects.¹⁸

Consulting with a healthcare provider who can discuss what treatments might work best for you, through personalised medicine, is recommended.¹⁹

THC vs CBD (cannabidiol)

Cannabidiol is another chemical found in cannabis which increases the amount of dopamine available. It can help patients to relax, and has less of a psychotic effect compared to THC.

Research specifically focusing on CBD and depression is scarce. Despite this, it remains a topic of interest as CBD may result in fewer side-effects overall (e.g., reduced weight gain).²⁰

Implications for medical use and public health

Considerations for medical marijuana in treating depression

The use of medical cannabis may be suitable for patients that are resistant to treatment with SSRI drugs in depression. In order to maximise the benefits, the dosage and delivery methods must be regulated to make sure that side-effects are kept to a minimum. 

Public health concerns

If not monitored properly, THC use can be dangerous due to drug dependence. This could lead to worsening symptoms of depression and a reliance on THC. 

Smoking cannabis can also lead to respiratory problems, so individuals who are considering this treatment must ensure they understand the potential risks.²¹

Summary

Depending on the dosage, THC may help to reduce the impact of negative emotional responses often seen in depression – although research into its effects are ongoing. It is important to consult with a healthcare professional as higher doses can lead to psychosis. 

Further research into medical cannabis as a treatment for depression should include a wider population of patients, ensuring any side-effects are monitored.

Depression is a complex disorder requiring a multimodal treatment approach. THC may help to reduce the symptoms of depression, but it might not tackle the root causes. It is vital for patients to have a personalised plan including other treatment methods, such as cognitive behavioural therapy, and discussion with a qualified healthcare professional is paramount.