Depression and Medical Cannabis

Depression is one of the most prevalent mental health conditions around the world. In the UK, 25% of people in England will experience a mental health problem like depression each year. At least 3 in 100 people are diagnosed with depression each week in England, but only 1 in 8 adults with mental health problems will seek professional help.

Mental health issues like depression are often still misunderstood, leading to people suffering in silence. There are times when short-term depression is a rational response to a situation, such as the loss of a loved one or a drastic change in circumstances. However, depression can also be a chronic and severe condition throughout a person’s life.

The severity of depression is measured by its impact on your daily life. If you’re unable to get through day-to-day life because of your symptoms, it’s likely that you need help to treat severe depression. The condition can interfere with all areas of your life, from struggling with work or school to no longer socialising with family or friends.

What happens when you have depression?

Depression is not simply feeling a bit sad. Everyone feels down sometimes, which is completely normal. When a person has depression, they feel persistently down for weeks or months on end. This constant low mood and feelings of hopelessness can drastically change their behaviour.

Symptoms of depression include low self-esteem, lack of motivation, and feelings of guilt or worry. You can range from feeling tearful and sad to irritable and annoyed at others around you. These mental problems can actually affect you physically in many ways, including:

• Speaking or moving more slowly
• Changes in appetite and losing or gaining weight
• Disturbed sleep and lack of energy during the day
• Constipation and digestion issues
• Unexplained aches or pains
• Low libido (sex drive)
• Menstrual cycle changes

The worse the mental and physical symptoms get, the more likely it is that the person will have thoughts of self-harm or even suicide. If you are having such thoughts, or know someone else who is suicidal, please contact a mental health helpline for support.

Depression can also be a symptom of another condition, such as Seasonal Affective Disorder or Bipolar Disorder. Most forms of depression can be triggered by life-changing events, though many also have a genetic factor – you’re more likely to develop depression if there’s a history of the condition in your family. With depression being such a pervasive health issue, it’s not surprising that many people are interested in the use of cannabis to treat depression.

Medical cannabis and depression: what does the evidence say?

There are two main chemicals found in marijuana that are of particular interest for therapeutic use. Tetrahydrocannabinol (THC) can cause a euphoric high, while cannabidiol (CBD) can perform the same pharmacological actions as THC without psychoactive effects.

It’s thought that these cannabinoids can help to relieve some of the physical and mental symptoms of depression and other conditions that often occur at the same time, such as chronic pain and anxiety. In addition to low mood, depression often manifests with physical pain throughout the body. If cannabis can elevate mood and reduce pain, then this could be a valid treatment.

However, scientific research is required to fully understand how cannabis affects the body and brain, and how this can specifically treat depression. Here are some examples of research into this area over the past 13 years, identifying the potential of medical marijuana for depression:

• 2008 – A mini-review on rodent studies trialling the therapeutic effects of cannabinoids on depression suggested that altered endocannabinoid levels and receptors in the body could be a cause of depression, noting that improving these with cannabinoids reduced symptoms.¹
• 2009 – A review of pre-existing data on the role of the endocannabinoid system in depression and anxiety found that blocking or genetic deletion of CB1 (Cannabinoid Type 1) receptors can cause affective (mood) disorders, and that augmentation of endocannabinoid signalling can reduce depression and anxiety.²
• 2010 – A study on mice reported that cannabinoids, including CBD and THC, caused ‘significant antidepressant-like effects’ at specific doses, due to the ‘mood-elevating properties’ of cannabis.³
• 2014 – A review concluded that CBD could help treat depression because it can affect 5-HT1A serotonin receptors (depression is believed to be caused by a serotonin imbalance in the brain).⁴
• 2014 – A study on rats by the Research Institute on Addictions at the University of Buffalo found that cannabis compounds may alleviate symptoms of depression by restoring endocannabinoid function.⁵
• 2016 – A review linked endocannabinoid system dysfunction to depression and comorbid pain, suggesting further study into the effects of endocannabinoids and depression pathways in the body.⁶
• 2018 – A study using data from the Strainprint app (used for tracking medical cannabis) found that high CBD/low THC cannabis caused a perceived short-term reduction in depressive symptoms. Users of medical marijuana perceived a 50% reduction in depressive symptoms and a 58% reduction in anxiety – however, there were variations between sexes, and indications that long-term use could lead to worsening symptoms.⁷
• 2018 – A review of studies into therapeutic CBD stated that the cannabinoid has neuroprotective properties that can reduce the symptoms of many clinical conditions, including depression. The researchers recommended further controlled trials for specific neuropsychiatric populations.⁸
• 2019 – A review on the antidepressant effects of CBD suggested that it can increase Brain-Derived Neurotrophic Factors, thereby reducing depression symptoms – but recommended further studies.⁹
• 2020 – A study by the University of Mexico using data from the Releaf cannabis-tracking app reported that individuals with depression experienced a significant improvement within minutes of consuming cannabis buds (with symptoms improving by almost 4 points on a scale of 1-10). While some experienced a lack of motivation as a result of THC, others were 3 times more likely to experience feelings of optimism, happiness, peacefulness, and relaxation.¹⁰

Since this line of research is still fairly young, under-represented, and ongoing, there is, unfortunately, a limited number of published clinical studies on humans. From the evidence that does exist so far, we know that high-CBD cannabis can decrease the severity of depression, while high-THC cannabis can alleviate stress and anxiety – albeit as a short-term treatment.⁷

These studies and reviews indicate a complex relationship between medical cannabis and depression, but confirm the promise of cannabinoids for relieving depressive symptoms. The more widely-spread information about the efficacy of medical marijuana for depression is usually case-based, and the effects can vary according to the strain and dosage.

Depression and the endocannabinoid system

So, what do we know about how exactly cannabis can improve the symptoms of depression? Cannabinoids work by upregulating the body’s endocannabinoid system (ECS), which may be dysfunctional due to a medical condition. Humans actually produce endogenous cannabinoids (endocannabinoids), with cannabinoid receptors throughout the body.

While CB1 receptors are primarily found in the central nervous system (CNS), CB2 receptors are found throughout the immune system.¹¹ Both CBD and THC can interact with these receptors to impact neurological signals. However, THC attaches most strongly to CB1 receptors, affecting cognitive processes including mood and appetite. CBD can strongly affect CB2 receptors, stimulating endocannabinoid production and reducing inflammation and pain.¹²

This information suggests that CBD may be most useful in situations where depression is comorbid with chronic pain, especially where the former may be a result of the latter. Where the most severe symptoms are persistent dysphoria (unhappiness), THC may be better to lift the mood and reduce tension and stress, which could be most useful when depression is comorbid with anxiety.

If depression occurs or worsens when there is a fault with ECS receptors, as research suggests, then activating the endocannabinoid system with the use of medical cannabis could help to reduce the resulting symptoms. The issue lies in the fact that not everyone reacts to cannabinoids the same way, and the wrong dose or over-use can end up causing downregulation in some cases. For this reason, it’s important for an expert to tailor the dosage and treatment plan to each individual.

How does cannabis compare to current treatments for depression?

There are several recommended treatments for depression, with doctors usually only prescribing anti-depressant medications if the condition does not improve following other treatments. Here are some of the possible treatments for moderate to severe depression:

• Talking therapy – such as counselling or CBT (Cognitive Behavioural Therapy) to help you discuss your problems and find solutions
• Lifestyle changes – things like quitting smoking or drinking alcohol, getting more exercise, and eating healthier foods are recommended to improve mood and overall health
• Self-help – using mental health apps to monitor and address symptoms or attending local support groups to meet other people in similar circumstances (known as peer support)
• Medication – prescription antidepressants such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin-noradrenaline reuptake inhibitors)

Many people use a combination of these, such as talking therapy and medication, to manage moderate chronic depression. It can take several weeks or months for anti-depressants to reduce symptoms, while certain forms of cannabis have been shown to take effect much faster.¹⁰ However, cannabis may also interact with anti-depressant medications, so it’s not recommended to use both at the same time until further research has been done.

Currently, medical professionals in the UK can prescribe medical cannabis for pain relief, but only for cancer patients, or those with chronic pain who have exhausted other treatment routes. As clinical trials continue, we must wait to learn more about the relationship between depression and cannabis use dependency before cannabinoids can become an accessible treatment option for depression and other mood disorders.

Due to the situation at present, it may only be possible to access cannabis to treat depression if you experience chronic pain and no other treatment has been effective at providing relief from your symptoms. The specialist doctors and consultants at Cannabis Access Clinics can assess your condition to determine the suitability of cannabis treatments for your depression. Click here to learn more about the process, or click here to book an eligibility consultation with our expert team.

References:

1) Mangieri, R. (2008). ‘Animal research highlights a therapeutic potential of cannabinoids for the treatment of depression’. Medical Cannabis and Cannabinoids, 3(2), pp. 4-7.

2) Patel S, Hillard CJ. (2009) ‘Role of endocannabinoid signaling in anxiety and depression’. Current Topics in Behavorial Neurosciences, 1, pp. 347-371.

3) El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S. (2010). ‘Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L’. Pharmacology Biochemistry and Behavior, 95(4), pp. 434-442.

4) de Mello Schier AR, de Oliveira Ribeiro NP, Coutinho DS, Machado S, Arias-Carrión O, Crippa JA, Zuardi AW, Nardi AE, Silva AC. (2014). ‘Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa’. CNS & Neurological Disorders Drug Targets, 13(6), pp. 953-960.

5) Haj-Dahmane S, Shen RY. (2014) ‘Chronic stress impairs α1-adrenoceptor-induced endocannabinoid-dependent synaptic plasticity in the dorsal raphe nucleus’. Journal of Neuroscience, 34(44), pp. 14560-14570.

6) Huang WJ, Chen WW, Zhang X. (2016). ‘Endocannabinoid system: Role in depression, reward and pain control (Review)’. Molecular Medicine Reports, 14(4), pp. 2899-2903.

7) Cuttler C, Spradlin A, McLaughlin RJ. (2018). ‘A naturalistic examination of the perceived effects of cannabis on negative affect’. Journal of Affective Disorders, 235, pp. 198-205.

8) Crippa JA, Guimarães FS, Campos AC, Zuardi AW. (2018) ‘Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age’. Frontiers in Immunology, 9, p. 2009.

9) Silote GP, Sartim A, Sales A, Eskelund A, Guimarães FS, Wegener G, Joca S. (2019). ‘Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms’. Journal of Chemical Neuroanatomy, 98, pp. 104-116.

10) Li X, Diviant JP, Stith SS, Brockelman F, Keeling K, Hall B, Vigil JM. (2020). ‘The Effectiveness of Cannabis Flower for Immediate Relief from Symptoms of Depression’. The Yale Journal of Biology and Medicine, 93(2), pp. 251-264.

11) Rahn EJ, Hohmann AG. (2009). ‘Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside’. Neurotherapeutics, 6(4), pp. 713–737.

12) Pertwee RG. (2008) ‘The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin’. British Journal of Pharmacology, 153(2), pp. 199-215.