Depression

Medical Cannabis and Depression

Definition

Alongside anxiety, insomnia, and chronic pain, depression is one of the most common reasons patients utilize medical cannabis and cannabidiol (CBD). This is not surprising, as depression is a common problem that manifests alongside many other conditions. Depression is also associated with stress and inflammation.

What is Depression?

Depression could be one of the most common types of mental health condition in the U.S. An estimated 21 million (8.4%) adults in the U.S. had at least one major depressive episode. In 2020, 14.8 million (6.0%) U.S. adults aged 18 or older had at least one major depressive episode with severe impairment.

Depression can range from mild to severe and is a persistent sadness that lasts weeks, months, or years rather than just a few days. Unhappiness, hopelessness, anger, and anxiety are all associated with long-term depression (major depressive disorder).

Depression is a pernicious condition and is often comorbid with anxiety disorders. As depression is also a feeling that is hard to define, it is also extremely difficult to treat directly. Symptoms such as the anxiety associated with depression are treatable, but the depression itself is a much more elusive matter.

The costs of depression cannot be underestimated and have a similar effect to that of smoking, i.e., a 7–11 year reduction in life expectancy. Suffering from depression can also increase the likelihood of developing another illness or disease as the immune system is dampened. Those in chronic pain are also more likely to develop depression, which can make the pain worse.

Brief Summary of Current Treatments

Typical first-line treatments include improvements in diet, exercise, regulating sleeping patterns, and mind-body techniques like meditation.

Contemporary antidepressants have a very high therapeutic index and are not highly addictive. They work by increasing neurotransmitters like serotonin (selective serotonin reuptake inhibitors or SSRIs) and noradrenaline (noradrenaline and specific serotonergic antidepressants or NASSAs). The increasing levels of neurotransmitters may also disrupt pain signals, making them a mainstay in treating chronic pain conditions.

For depression that is resistant to lifestyle changes and antidepressants, other prescription medications may be prescribed. These usually include benzodiazepines (especially for depression with anxiety) or tricyclic antidepressants (TCAs).

Various kinds of therapy can also be employed, such as cognitive-behavioral therapy (CBT), behavioral action, interpersonal therapy (IPT), mindfulness-based cognitive therapy (MBCT), psychodynamic psychotherapy, and eye movement desensitization and reprocessing (EMDR). Guided self-help is also a commonly-offered treatment.

How Might Medical Cannabis Help?

Antidepressants can take some time to work, and figuring out which ones work can mean months or even years of trying different pills. Furthermore, some prescription medications can have adverse side effects, such as weight loss or weight gain, appetite changes, excessive sweating, tremors, headaches, joint pain, nausea, GI upset, and, in rare cases, an increased risk of suicide.

Cannabinoids, meanwhile, provide a more immediate effect, so they can be seen relatively quickly if the cannabinoids help. As cannabinoids such as CBD also work on serotonin receptors (specifically 5HT1A), they could have antidepressant-like qualities. Medical cannabis, which contains a combination of cannabinoids, terpenes, and flavonoids with potential therapeutic applications, could also help manage anxiety, insomnia, and chronic fatigue associated with depression.

However, it is essential to remember that cannabinoids have biphasic effects, meaning they can have different effects at different dosages. For those with anxiety alongside depression, microdosing THC may be useful, but too high a dose may prompt anxiety and increase the feeling of being “low.” This gives a clue as to why the research into cannabis use and depression seems to return such differing results, with some claiming it helps and other studies showing a correlation between cannabis use and an increase in the rates of depression in a population.

This is certainly one area where regulation can help, as people are more easily able to shop for a product that will help them rather than be beholden to whatever strain (more accurately called “cultivar” or “chemotype”) or product their seller has that particular day.

There are also several other issues to be concerned about when looking at depression, which is a complex condition to define precisely. Contemporary antidepressants may work well for anxiety and symptoms associated with depression, but not necessarily the depression itself, which is a far more nebulous condition to treat.

That antidepressants don’t work for everybody and often need to work on receptor systems other than serotonergic ones suggests that serotonin imbalances are not alone in the formation of depression. It is unlikely that a malformation in one set of genes encoding serotonin receptors is the leading cause of depression.

We cannot say that modulating the endocannabinoid system (ECS) is a better answer: Most evidence is pre-clinical, as with many studies on cannabis for specific health problems. But the fact that cannabinoids work on multiple receptor targets may give us a clue as to how specific conditions with polygenetic causes arise and how best to treat them.

Cannabinoids

The following phytocannabinoids (plant cannabinoids) may be useful for managing depression:

• Tetrahydrocannabinol (THC): low-to-moderate doses
• Cannabidiol (CBD) and cannabidiolic acid (CBDA/CBDa): moderate-to-high doses
• Cannabichromene (CBC): has antidepressant and anti-anxiety (anxiolytic) effects
• Cannabinol (CBN): has sedative effects, which could be useful for those with insomnia alongside their depression
• Cannabigerol (CBG): has antidepressant effects
• Tetrahydrocannabivarin (THCV): could have uplifting effects in low doses

Cannabinoid Ratios

Note that all cannabinoid ratios should be THC:CBD to reduce confusion. Some products may put the CBD first on their label if it is in higher concentrations (e.g., CBD:THC 3:1), so be sure to check the label. The following THC:CBD ratios could also be helpful:

• 1:20
• 1:3
• 1:1

Terpenes and Terpenoids

• Pinene: has refreshing, uplifting, and relaxing effects
• Beta-caryophyllene: has stress-busting and anxiolytic effects
• Limonene: has stimulating and relaxing effects
• Nerolidol: has calming effects

Such terpene content may have stimulating effects, especially if combined with CBD and CBG and low-to-moderate doses of THC. However, those with depression without anxiety may be slightly more tolerant of THC.

Flavonoids

Flavonoids can bust stress, and the cannabis plant is full of them. Several flavonoids found in cannabis could have anti-anxiety and antidepressant effects, including naringin, luteolin, kaempferol, and apigenin.

Effective Ways of Taking Medical Cannabis for Depression

Routes of Administration

• Inhalation
• Tincture
• Edibles and drinkables (ingestion)

Special Formulations

Choosing a variety of cannabis with stimulating, uplifting effects would be ideal. Some equatorial sativas may be helpful for this, but technically any type of cannabis, indica or sativa, could have such effects. Cannabis varieties (chemotypes) with balanced THC:CBD profiles, phytocannabinoids (plant cannabinoids) like CBG and low doses of THCV, and terpenes like beta-caryophyllene, limonene, pinene, and nerolidol could be helpful.

Cultivars that could be useful for depression include Blue Dream, Strawberry Cough, Green Crack (Green Crush, Mango Crack), Jack Herer, Harlequin, Lucid Blue, Harlequin, and Durban Poison. However, these are just anecdotal reports.

Dosing Method

Using a vaporizer or inhaler could be useful for immediate relief.

Tinctures can be helpful for longer-lasting relief.

Edibles may provide substantial and long-lasting effects but should be microdosed to avoid adverse effects.

Possible Adverse Effects

• Cannabis may induce a depressive episode in some, especially if very high doses of THC are taken.
• In those who suffer from anxiety alongside depression, consumption of high doses of THC may trigger an anxiety or panic attack.
• Overconsumption of cannabis may induce dizziness, fatigue, nausea/vomiting, and/or headaches.

What are the Pros and Cons of Taking Medical Cannabis for Depression?

Despite being well-tolerated by the human body, there are possible pros and cons with medical cannabis, just like any other medication.

Potential Pros

• Cannabinoids have antidepressant-like actions, which could help those resistant to antidepressants and possibly even reduce or replace their usage.
• Antidepressants have side effects such as nausea, vomiting, and headaches/migraines, which cannabis can help alleviate.
• Cannabinoids work quicker than antidepressants, making them potentially very valuable for depressive episodes in the short term.
• Cannabis can be beneficial for depression arising from chronic pain.
• The cannabis plant contains many stress-busting compounds, such as limonene, alpha- and beta-pinene, and linalool, alongside CBD and THC.
• Medical cannabis could be helpful for depression with anxiety.

Potential Cons

• Care must be taken if the depression is comorbid with anxiety, where the person may be more sensitive to THC.
• Getting the dosage right is important: Too high a dose of THC could make depressive episodes worse, while a low dose may help alleviate depression to some extent.
• In some instances, high amounts of cannabis use may be implicated in the development of depression. This seems to be the case with high-THC use during the teenage years.
• Contemporary antidepressants aren’t usually contraindicated by cannabis, but older ones like tricyclic antidepressants (TCAs) are.

Useful Anecdotal Information

• Why People Smoke Weed to Treat Depression
• More Are Turning to Pot When Depressed – But Does It Help or Harm?
• “When they say weed causes depression, but it’s your fav antidepressant”: Knowledge-aware attention framework for relationship extraction

Scientific Data Overview and Studies

• Total Studies = 104
• Positive Studies = 66
• Inconclusive Studies = 26
• Negative Studies = 12
• 69 Meta-Analyses (35 positive, 22 inconclusive, 12 negative); 27 Animal Studies (25 positive, 2 inconclusive); 3 Double-Blind Human Trials (2 positive, 1 inconclusive); 2 Human Trials (1 positive, 1 inconclusive); 3 Lab Studies (all positive)
• 28 studies include CBD (25 positive, 3 inconclusive); 7 studies include THC (5 positive, 2 inconclusive); 1 study includes CBC (positive); 1 study includes CBG  (positive); 1 study includes CBDa (positive); 1 study includes CBN (positive).
• No. of Leafwell Patients (2021) = 3,354
• Possible Overall Efficacy: Moderate

Quotes from Studies

“The endocannabinoid system plays a key role in emotional responses and cognition function, and both clinical and preclinical studies suggest that dysregulation of its neuronal signaling may be involved in the pathophysiology of these disorders [anxiety, depression, schizophrenia] [27,28]. Thus, therapeutic strategies based on drugs that modulate endocannabinoid signaling may be useful in the treatment of neuropsychiatric disorders.” Source: Scherma, Maria, et al. ‘New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders‘ Medicines (Basel, Switzerland) vol. 5,4 107. 2 Oct. 2018, doi:10.3390/medicines5040107

“… [B]rain wave activity and ANS are affected by the inhalation of the EO [essential oil] of Cannabis sativa suggesting a neuromodulator activity in cases of stress, depression, and anxiety.” Gulluni, Nadia, et al. ‘Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects,’ Evid Based Complement Alternat Med. 2018 Jan 17;2018:1709182. doi: 10.1155/2018/1709182. eCollection 2018.

“CBD induces cellular and molecular changes in brain regions related to depression neurobiology, such as increased Brain Derived Neurotrophic Factor (BDNF) levels and synaptogenesis in the medial prefrontal cortex, as well as it increases neurogenesis in the hippocampus.” Silote, Gabriela Pandin, et al. ‘Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms,’ J Chem Neuroanat. 2019 Jul;98:104-116. doi: 10.1016/j.jchemneu.2019.04.006. Epub 2019 Apr 27.

Conclusion

Although there are inconclusive results and some negative results, in general, medical cannabis could be seen as an antidepressant if carefully dosed. However, more clinical trials need to occur, as most studies so far are preclinical studies or meta-analyses based on data that could be somewhat biased.

Related Articles

• Medical Cannabis and Bipolar Disorder (formerly known as manic depression)
• The Science Behind Medical Cannabis and Depression
• Is Marijuana a Depressant?
• Cannabis and Postpartum Depression (PPD)
• Medical Cannabis and Anxiety & Panic Disorders
• Cannabis, Stress, and Inflammation: Targeting the ECS for a Range of Health Problems

Note that the information in this article does not constitute medical advice.

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