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Cannabis and depression: a complex association

Picture of Fabio Turco

Screenshot 2024-01-20 at 14.52.27

 

In recent years, the debate on the use of cannabis in depression, both as a cause and as a possible cure, has attracted great interest.

Depression is a complex mood disorder that affects millions of people around the world, with serious consequences for mental and physical health. Various studies have highlighted a correlation between cannabis use and depression, especially among adolescents.

However, other factors such as age at initiation of use, socioeconomic variables, and genetic factors may influence this association.

Furthermore, some preclinical studies suggest that the cannabinoids present in cannabis could have antidepressant effects through modulation of brain receptors. What stage is scientific research on the correlation between cannabis use and depression?

 

INDEX

 

1. What is depression and how does it manifest itself

Depression, or depressive disorder, is a complex mood disorder that profoundly affects an individual's health and well-being. It can manifest itself in various forms and intensities, significantly influencing the lives of those who suffer from it.

Depression is one of the most common mental illnesses globally, with a significant impact on public health. According to the World Health Organization (WHO), more than 264 million people worldwide suffer from depression. It is estimated that this disorder is among the main causes of disability in the world and can lead to serious consequences for physical and mental health.

In Italy, depression represents a significant problem in terms of mental health. According to recent data from the National Institute of Statistics (ISTAT), approximately 7.8% of the Italian population has suffered from depression at least once in their life. The prevalence is higher in women than in men. Depression affects people of all ages, but is more common among young adults and older adults.

 

1.2 What are the symptoms of depression?

Depression has a significant impact on the lives of people affected by it. It can affect interpersonal relationships, work and school performance, quality of life and physical health. People with depression may experience these symptoms:

  • difficulty carrying out daily activities,
  • loss of interest in things they usually found pleasurable (anhedonia),
  • constant feelings of sadness and despair,
  • reduction in self-esteem,
  • social isolation,
  • concentration problems,
  • sleep and appetite disorders,
  • increased risk of suicidal ideation.

 

1.3 What are the types of depression?

When the symptoms are such as to compromise social adaptation, we speak of major depression, the most common form of depression, which manifests itself with:

  •  episodes of deep sadness,
  •  loss of interest,
  •  tiredness,
  • feelings of guilt,
  •  low self-esteem.
     

In addition to major depression, there are various types of depression. The main ones include:

  • Reactive depression, which develops following a triggering event, such as the loss of a loved one, a separation, a failure, a romantic or professional disappointment, the loss of a job, exposure to psychophysical violence or being the victim of a fraud. In this case, the symptoms manifested are excessively intense and prolonged compared to the triggering cause.
  • Endogenous depression, which cannot be attributed to conscious or semi-conscious triggering events, as in the case of reactive depression, but to causes of a genetic-biological or unconscious nature.
  • Persistent depression (dysthymia) is a form of chronic depression characterized by less intense but long-lasting sadness.
  • Peripartum depression affects women during and after giving birth.
  • Seasonal depression, linked to seasonal changes.
  • Bipolar (or psychotic) depression, which alternates between episodes of depression and mania.

 

1.4 Depression: causes and treatments

The biological causes of depression are still partly unknown. It is probably caused by an imbalance in the hypothalamic-pituitary-adrenal axis, which regulates the response to stress. While in the past it was thought to be due to an imbalance in brain serotonin levels, today we know that other neurotransmitters, such as norepinephrine and dopamine, are also involved.

According to the stress diathesis hypothesis, depression can be considered as an inability of the brain and endocrine system to react to life changes or sources of stress that exceed the individual's tolerance limits. What is clear is that depression is a complex disease, with multiple causes and involving a network of neural systems. Recent studies have highlighted metabolic alterations in different regions of the brain, such as:

  •  the paralimbic prefrontal cortex,
  •  the anterior cingulate gyrus,
  •  the anterior temporal cortex,
  •  the basal ganglia,
  •  the amygdala,
  •  the thalamus.

Many people can get relief from depression. Treatment may include a combination of psychological therapy and pharmacotherapy.

Cognitive-behavioral therapy (CBT) is a form of psychotherapy widely used to treat depression, in which the patient works with a therapist to identify and change negative thought patterns and harmful behaviors.

Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), may be prescribed by a doctor to help reduce depressive symptoms.

In addition to psychotherapy and pharmacotherapy, other measures such as adopting a healthy lifestyle, social support, regular exercise and stress management can be useful in case of depression.

 

2. Association between cannabis use and depression

Some studies indicate an association between cannabis use and depression, especially among adolescents. [1] The age at which cannabis use began seems to play an important role in the association with depression. Early cannabis use (under 18) has been associated with an increased risk of developing future depression, both among frequent and occasional users. [2]

In contrast, late use of cannabis does not appear to be significantly associated with an increased risk of developing depression. [3]

It should be noted, however, that if socioeconomic variables - such as income and education - are also taken into consideration among the various participants in the studies, the association between cannabis use and depression is reduced, both in adults and in adolescents. [4]

Genetic and environmental factors can also influence the relationship between cannabis and depression. Several polymorphisms and genetic variants have been identified that are correlated with both depression and cannabis abuse. [5]

This does not indicate that cannabis directly causes depression. According to scholars, many people suffering from depression tend to use cannabis to improve depressive symptoms. Hence the strong correlation between cannabis use and depression. Additionally, those who consume large amounts of cannabis may appear depressed due to the drug's dulling effect.

In general, the various studies analyzed seem to indicate that various sociodemographic and clinical factors appear to be responsible for the development of depression, rather than the use of cannabis itself, although massive and prolonged use over time seems to increase the risk of developing depressive symptoms.

 

3. Cannabis as an antidepressant: what the pre-clinical studies say

Several preclinical studies have shown that cannabis could be an effective therapy against depression. [6]

This effect could be mediated by the effect of cannabinoids on central CB1 receptors. Various studies on laboratory animals have shown that modulation of CB1 receptors can induce effects similar to those of antidepressants. Furthermore, depressed patients treated with selective serotonin reuptake inhibitors (SSRIs) showed a reduction in the expression of CB1 receptors in the anterior cingulate cortex, suggesting that increased expression and activation of this receptor could have antidepressant properties. [7]

Furthermore, an association has been demonstrated between polymorphisms of the CNR1 gene (which codes for the CB1 receptor) both with a greater vulnerability to develop a depressive episode following a stressful event and with an increased risk of resistance to the effects of antidepressants [8] [9]

Thus, most preclinical studies indicate that a defect in endocannabinoid signaling may be associated with depression and, therefore, acting on the endocannabinoid system could be an effective treatment for depression.

 

4. Cannabis against depression: what clinical studies report

Many studies report that cannabis is often used as self-medication for depression. [5]

Furthermore, individuals who use cannabis occasionally or even daily show lower levels of depressive symptoms than those who have never tried cannabis [10].

Several observational studies have also shown clear evidence of a cannabis-induced improvement in mood in depressed patients [11].

An analysis of 129 patients included in the UK Medical Cannabis Registry revealed that treatment with cannabinoids was associated with a reduction of the severity of depression at 1, 3 and 6 months, although limitations in the study design do not allow a causal association to be determined. [12]

Cannabidiol (CBD) may also be helpful for depression. In fact, low serotonin levels are likely linked to depression. CBD doesn't necessarily increase serotonin levels, but it can affect how receptors in the brain respond to serotonin already in the system. A 2018 review of the scientific literature concluded that CBD has anti-stress effects that can reduce depression when it is linked to stressful events. [13]

Although cannabis and CBD have reported positive effects in patients with depression, other studies have observed that reducing cannabis use may be associated with a reduction in depressive symptoms, but not in overall quality of life. [14]

 

5. The conclusions: does cannabis cause depression or cure?

It is not possible to give a single answer to this beautiful question.

It has been observed that the use of cannabis can influence the course of depression. Some studies have suggested that cannabis use may increase depressive symptoms, compromise the effectiveness of drug treatment, and reduce quality of life among patients with depression. Other studies have reported a reduction in depressive symptoms after cannabis use, although it is important to consider that chronic and heavy use could have long-term negative effects on depression.

Preclinical studies suggest that cannabis may have a therapeutic effect on depression.

The effect of cannabinoids on CB1 receptors in the central nervous system could mediate this positive action. In any case, it is important to emphasize that further research is needed to fully understand the role of cannabis in the management of depression and to evaluate its potential benefits and risks. In particular, well-designed clinical trials are needed to evaluate the effectiveness of cannabis against depression, long-term safety, and interactions with other treatments for depression.

Before using Medical Cannabis as a therapy, it is advisable to consult a qualified medical professional for an individual evaluation and discussion of potential risks and benefits.

 

References

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    The persistence of the association between adolescent cannabis use and common mental disorders into young adulthood.
    Addiction 108(1):124–133.
  2. Chantelle T White, Humaira Shamim, Roba Al Shouli, Ahmad B Habbal, Lubna Mohammed.
    Cannabis Use and the Development of Depression in Adolescents: Is There an Established Linear Relationship Between the Two?
    Cureus. 2022 Jul 28;14(7):e27394.
  3. Guttmannova K, Kosterman R, White HR, Bailey JA, Lee JO, Epstein M, Hawkins JD (2017).
    The association between regular marijuana use and adult mental health outcomes.
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    Bidirectional associations between cannabis use and depressive symptoms from adolescence through early adulthood among at-risk young men.
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    J Neural Transm 114:1055–1063
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  9. Juhasz G, Chase D, Pegg E, Downey D, Toth ZG,

    Stones K, Platt H, Mekli K, Payton A, Elliott R et al (2009).
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    Neuropsychopharmacology 34:2019–2027

  10. Denson TF, Earleywine M (2006).
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  14. Yih-Ing Hser, Larissa J Mooney, David Huang, Yuhui Zhu, et al.
    Reductions in cannabis use are associated with improvements in anxiety, depression, and sleep quality, but not quality of life.
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