Medical Cannabis and Depression

Depression is a mood disorder characterized by a persistent low mood. Depression can range from mild to severe and lasts much longer than temporary sadness—weeks, months, or even years. Feelings of unhappiness, lack of motivation, hopelessness, frustration, low self esteem, and anxiety often come with it, which is also known as major depressive disorder (MDD).

While depression can be tough, it’s highly treatable. Many people experience anxiety alongside depression, making things feel overwhelming. But with the right treatment and understanding of symptoms, relief is possible.

Depression is one of the most common mental health conditions in the U.S. Around 21 million adults—8.4% of the population—had at least one major depressive episode in 2020. In 2021, 14.5 million people experienced a depressive episode with serious impacts on daily life. Women are more affected than men, and young adults (18-25) experience depression the most.

Many turn to medical cannabis and CBD to manage depression, especially when it’s linked with anxiety, insomnia, or chronic pain. Depression often shows up alongside stress and inflammation, but the key is that it can be managed effectively with the right support.

Download Guide To Depression and Medical Cannabis

Depression Causes

Depression can be incredibly complex, with causes that aren’t always easy to pinpoint. Sometimes, there’s no clear trigger, which can make it even more frustrating for those trying to understand why they’re feeling the way they do.

For some, it’s a perfect storm of events, while others may be more naturally prone to depression without a specific reason.

Still, there are several common factors that can play a significant role:

• Trauma
• Problems with family or peer relationships
• Isolation
• Alcohol and drugs
• Stressful life events such as loss of a loved one, divorce, or an accident
• Disease
• Chronic pain

Genetics and family history may make one more prone to developing depression.

Depression Symptoms & Health Effects

Symptoms of depression typically include:

• Persistent sad, anxious, or “empty” mood.
• Feelings of hopelessness or pessimism – a sense of “doom”.
• Feelings of irritability, anger, or frustration.
• Restlessness.
• Changes in appetite – increase or decrease in hunger.
• Insomnia (lack of sleep) or hypersomnia (oversleeping).
• Feelings of guilt or helplessness.
• Feelings of unimportance or worthlessness.
• Loss of interest or pleasure in hobbies and activities.

What Patients Say About Their Symptoms

Depression Diagnosis

For those experiencing depressive symptoms persistently (most of the day, nearly every day, for longer than 2 weeks), a primary care provider may make a referral to a psychiatrist for an official diagnosis and to develop an appropriate treatment plan.

Depression Prognosis

The costs to a person’s quality of life from 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, because the immune system is negatively impacted. Those in chronic pain are also more likely to develop depression, which can make the pain worse.

Depression Treatments

Depression is most commonly managed with a mixture of lifestyle changes (improved diet, increased physical activity, regulated sleep patterns), therapy, herbal remedies, and antidepressants. However, in some cases, different kinds of prescription medications may be required.

First-Line 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. Antidepressants work by increasing chemicals in the brain, called “neurotransmitters.” The main two neurotransmitters antidepressants increase are serotonin and norepinephrine, which regulate mood. The increasing levels of serotonin and norepinephrine may also disrupt pain signals, making them a mainstay in treating chronic pain conditions.

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.

Other Treatments

For depression that is resistant to lifestyle changes and standard antidepressants, other prescription medications may be prescribed. These usually include benzodiazepines (especially for depression with anxiety) or tricyclic antidepressants (TCAs). Monoamine oxidase inhibitors (MAOIs) may also be prescribed. However, these are not ideal for long-term use and can come with side-effects like dizziness, confusion, headaches, nausea, weight gain, drowsiness, insomnia, and increased risk of contraindications with other drugs. In some instances, hypertensive crises and addiction may occur.

Adjunctive Therapy & Alternative Treatments

Common adjunctive and alternative therapies for depression include physical activities such as Yoga and Tai Chi, mindfulness, music and/or art therapy, and acupuncture. Herbal remedies such as St. John’s Wort, chamomile, lavender, saffron, valerian, and golden or rose root may also be used to manage symptoms associated with depression and anxiety. However, the evidence for the efficacy of various herbal remedies for depression is mixed.

Cannabis for Depression

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

Cannabinoids, meanwhile, may provide a more immediate effect. This means that a patient can know relatively quickly if the cannabinoids help them. 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 of THC may prompt anxiety and increase the feeling of being “low.” This is likely why the research into cannabis use and depression seems to return such differing results, with some claiming it helps and other studies with sample sizes between 700 and 45,000 showing a correlation between cannabis use and an increase in the rates of depression.

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.

Antidepressants don’t work for everybody and other receptor systems sometimes need to be targeted. This suggests that serotonin imbalances are not alone in the formation 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 help patients and healthcare providers identify how specific conditions with multiple causes arise, and how best to treat them.

The following 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

Cannabis also contains many terpenes that may help manage depression, including:

• 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, some of those with depression without anxiety may be slightly more tolerant of THC. There is no one size fits all.

Other than cannabinoids and terpenes, flavonoids found in cannabis can bust stress. Several flavonoids found in cannabis could have anti-anxiety and antidepressant effects, including naringin, luteolin, kaempferol, and apigenin.

Additional Information for Patients

There are a variety of charities throughout the US focusing on education, research, advocacy, increasing awareness and understanding, and the treatment of depression and other mental illnesses. These include:

• National Alliance on Mental Illness (NAMI)
• Mental Health America (MHA)
• Child Mind Institute
• American Foundation for Suicide Prevention (AFSP)
• The Jed Foundation
• Sista Afya Community Mental Wellness
• Brain and Behavior Research Foundation
• Active Minds

Federal research agencies such as the National Institutes of Mental Health (NIMH) focus on researching mental disorders with the goal to increase understanding and treatment options.

Depression FAQs

What causes depression?

There are several possible causes of depression, and there is often more than one. Biological or genetic, psychological and/or environmental factors, or a combination of these, are thought to be the cause of depression.

Depression can be a result of a primary psychiatric condition, or it can be secondary to a medical condition such as cancer, Parkinson’s disease (PD), or hypothyroidism.

What are common symptoms of depression?

A mnemonic called “SIGECAPS” is often used to identify symptoms of major depressive disorder (MDD).

• Sleep problems (insomnia or hypersomnia)
• Interest loss
• Guilt
• Energy loss
• Concentration problems
• Appetite changes (increase or decrease in appetite)
• Psychomotor problems
• Suicidal ideation

This is by no means an exhaustive list. Anxiety is a common comorbidity with depression.

Is there a difference between sadness and depression?

Sadness is an everyday part of life. However, if the sadness becomes persistent and lasts longer than two weeks and is accompanied by symptoms such as cognitive difficulties, changes in sleep patterns and appetite, fatigue, feelings of guilt or worthlessness, hopelessness, and/or frustration/irritability, then it may be deemed major depressive disorder (MDD) instead.

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.

Can medical cannabis help manage anxiety associated with depression?

Medical cannabis contains many compounds that can help manage stress and anxiety alongside depression. These include cannabinoids like THC, CBD, and CBC, terpenes like beta-caryophyllene, pinene, and limonene, and flavonoids like luteolin, kaempferol, and apigenin. Together, these form an “entourage effect” that can help reduce anxiety and depression.

It is thought that these compounds in cannabis work together to modulate serotonin, dopamine, norepinephrine, and endocannabinoid signaling pathways, acting as a form of antidepressant and anxiolytic (anti-anxiety).