Can CBD Make Depression Worse? The Truth About CBD Treatment

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CBD oil has gained remarkable popularity in recent years, with sales reaching $2 billion US dollars in 2018. However, this widespread use raises an important question: could CBD oil potentially worsen depression symptoms in some individuals?

The numbers surrounding depression make this question particularly pressing. Major depressive disorder affects more than 300 million people worldwide, with approximately 280 million adults (5% of the global population) experiencing this condition. Since the COVID-19 pandemic began in 2020, depression cases have increased by 27.6%, particularly among younger people.

Despite this growing mental health crisis, research reveals concerning patterns about how people use CBD. Only 19% of CBD users consult a doctor or pharmacist before taking it, whilst most (59%) consume it daily. This lack of professional guidance becomes particularly worrying when considering CBD’s complex effects on mood and brain chemistry.

Although CBD is often promoted as a natural solution for mood disorders, the relationship between CBD and depression is far from straightforward. Some people may find relief, whilst others might experience worsened symptoms. Product quality, dosage, and individual biochemistry all influence whether CBD helps or harms someone with depression.

There is still much uncertainty around CBD’s effects on mental health conditions. What we do know is that the evidence is more complex than many marketing claims suggest. This article examines the scientific research to help you understand when and why CBD might make depression worse, and what you should consider before using it for mental health concerns.

How CBD works in the brain

To understand why CBD might sometimes worsen depression, we need to examine how this complex compound interacts with brain chemistry. Unlike many medications that target a single pathway, CBD affects multiple brain systems simultaneously.

CBD and the endocannabinoid system

The human body has a system called the endocannabinoid system that helps regulate various functions including mood, pain, and stress. This system contains two main types of receptors: cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). CB1 receptors are found throughout the brain and other tissues, whilst CB2 receptors appear primarily in immune cells with fewer in the central nervous system.

CBD is different from tetrahydrocannabinol (THC) – also a substance from the cannabis plant. Unlike THC, CBD has weak binding to both CB1 and CB2 receptors. Instead, it works as what scientists call a negative allosteric modulator of CB1 receptors. This means CBD can reduce endocannabinoid signalling by binding to a different site on the receptor and changing how other substances interact with it.

The body produces natural substances called endocannabinoids, including anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which bind to cannabinoid receptors. CBD acts like a ‘reuptake inhibitor’ that prolongs the natural lifecycle of our own endocannabinoids, potentially allowing them to have stronger effects. This mechanism may help buffer stress, but could also contribute to negative effects in some people.

Effects on serotonin and other brain chemicals

CBD’s influence on mood extends beyond the endocannabinoid system. Research shows that CBD interacts with serotonin receptors, specifically the 5-HT1A receptor. Through this interaction, CBD may reduce anxiety and help restore impaired serotonin function in certain conditions.

Studies suggest that repeated treatment with low doses of CBD can reduce anxiety through 5-HT1A receptor activation. CBD’s ability to affect stress, anxiety, and depressive symptoms may explain some of its potential therapeutic effects.

CBD also appears to influence dopamine activity in brain regions involved in motivation and reward. This differs markedly from THC, which can disrupt normal dopamine function and affect how we process important information. Interestingly, CBD may help normalise abnormal dopamine signalling, which could explain some of its potential benefits.

How CBD differs from THC

Although both come from cannabis plants, CBD and THC work very differently in the brain:

Receptor binding: THC binds directly to CB1 receptors as a partial agonist, producing psychoactive effects. CBD works differently, reducing the potency and effectiveness of substances that activate cannabinoid receptors.

Psychoactive effects: THC produces the characteristic “high” by binding with CB1 receptors in the brain, whereas CBD does not cause this intoxication. However, CBD still affects brain function – just not in the same way as THC.

Cognitive effects: THC can increase anxiety without affecting thinking abilities, whilst CBD may impair some cognitive functions in normal conditions but improve them when there are existing deficits.

When taken together, CBD can reduce many of THC’s undesirable effects on brain function and mood. This opposite action on CB1 receptors may be the main way CBD counteracts THC’s psychoactive side effects.

These complex brain mechanisms help explain why CBD might worsen depression in some individuals. Its effects depend on existing brain chemistry, dosage, and interactions with other medications or substances, making the response highly individual.

Can CBD oil help with depression?

Research into CBD oil for depression has produced both encouraging and contradictory results. Understanding the current scientific evidence is essential for anyone considering this supplement as a treatment option.

Animal studies showing promise

Laboratory research has consistently demonstrated CBD’s potential antidepressant properties in animal models. In multiple studies, CBD (30 mg/kg) reduced immobility time in the forced swimming test—a standard measure for evaluating antidepressant effects—with results comparable to the conventional antidepressant imipramine. This test places animals in water where reduced immobility indicates an antidepressant-like response.

The mechanism behind these effects appears particularly interesting. Pre-treatment with WAY100635, a selective 5-HT1A receptor antagonist, blocked CBD’s antidepressant-like action, suggesting these effects work primarily through serotonin receptor activation. CBD also appears to increase brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and promote synaptogenesis.

One study found that ineffective doses of CBD, when combined with sub-effective doses of fluoxetine or desipramine, produced significant antidepressant-like effects. This suggests CBD might work alongside conventional treatments, though much more research is needed to understand these interactions.

Human evidence remains limited

Despite promising animal research, human evidence is significantly more restricted. Only a handful of controlled clinical trials have examined CBD’s effects on depression, with mixed results.

A randomised, double-blind, placebo-controlled trial found that CBD could reduce depression severity in young people with treatment-resistant depression and showed an adequate safety profile. However, other clinical studies have shown contradictory outcomes. In a separate randomised, double-blind, placebo-controlled pilot study with bipolar depression patients, researchers found no significant difference in depression rating scores between placebo and CBD groups.

Observational data presents an equally complex picture. In one survey, users reported a 50% reduction in depression following cannabis use, with high CBD/low THC formulations associated with the largest improvements. Yet the same study noted that baseline symptoms of depression appeared to worsen over time.

Research limitations and concerns

Current evidence for CBD’s antidepressant effects has substantial limitations:

1. Methodological issues: Many studies employ different experimental protocols and small sample sizes, making meaningful comparisons difficult.
2. Self-selection bias: As noted in research, “Self-selection bias is increased by the significant patient interest in medical cannabis as these patients must be motivated to access the non-traditional medication system”.
3. Placebo effects: Self-reported assessments may be influenced by positive expectations of treatment.
4. Insufficient human data: According to multiple reviews, “Clinical evidence of CBD-antidepressant effects in people affected by depression does not exist” and “Regarding the effects of CBD on depression symptoms, further research is required to draw conclusions”.

Researchers conclude that “there is not enough research to support the evidence for the efficacy of CBD on depression”. The conflicting reports may reflect different experimental protocols, varying CBD concentrations, and individual biological differences.

If you’re considering using CBD oil for depression, you should speak to your GP or other healthcare professional to ensure it is safe and appropriate for you to do so. Given these research limitations, professional guidance becomes particularly important when considering whether CBD might help or potentially worsen your symptoms.

When CBD oil might make depression worse

Although CBD oil is often marketed as a natural remedy, mounting evidence suggests that it can potentially worsen depression symptoms in certain individuals. Understanding these risks is essential for anyone considering CBD oil as a treatment option.

Can CBD oil worsen depression in some users?

The package insert for Epidiolex, the FDA-approved form of CBD, explicitly lists depression and suicidal ideation as possible adverse reactions. Clinical trials involving 27,863 patients treated with Epidiolex and 16,029 patients on placebo showed concerning results – the risk of suicidal thoughts increased by 1 in every 530 patients, with four suicides occurring in the Epidiolex-treated group compared to none in the placebo group.

Individual responses to CBD oil vary considerably. Some users report improvements in anxiety and pain management, yet others experience mood swings or cognitive impairment when using CBD products. These varying response patterns make it difficult to predict who might experience worsening depression symptoms.

The American Psychiatric Association has taken a clear stance on this issue: “There is no current scientific evidence that marijuana is in any way beneficial for the treatment of any psychiatric disorder. Current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders”.

Reported cases of increased anxiety and low mood

Healthcare professionals now recommend consultation with a healthcare provider before starting CBD treatment, particularly for individuals with existing mental health conditions. This guidance stems from documented cases where CBD appeared to worsen symptoms in vulnerable populations.

One particularly concerning finding comes from studies investigating cannabinoids for hospitalised patients with unipolar or bipolar depression. These studies found no improvement in depression symptoms; instead, anxiety and psychotic symptoms emerged in more than 50% of patients.

Research examining different doses of nabiximols (a cannabis-based medicine containing both CBD and THC) discovered that high doses (11–14 sprays/day) actually worsened depression, suggesting higher concentrations of cannabinoids may promote depressive symptoms.

Dose-dependent effects and unexpected reactions

The relationship between CBD oil and depression appears to be significantly dose-dependent. Research suggests that low doses of cannabinoids may have anti-anxiety and antidepressant properties, whilst high doses are associated with increased anxiety and depressive symptoms. This biphasic effect helps explain the contradictory results found in scientific literature.

CBD’s interactions with the endocannabinoid system can be complex. CB1 receptor activation can have both depressant and anti-depressant activity, which may partially explain these contradictory results.

For those using CBD products, these unexpected reactions may manifest in several ways:

1. Higher doses of CBD increased anxiety symptoms in college students during test situations
2. CBD failed to reduce anxiety, alertness, and discomfort induced by trauma recall in some studies
3. Repeated CBD administration (300 mg for 2 weeks) might reduce anxiety symptoms, yet a single 300 mg dose did not show the same effect

These contradictory effects may be explained by individual biochemistry, pre-existing conditions, and medication interactions. For instance, CBD’s inhibition of cytochrome P450 enzymes can alter how the body processes certain antidepressants, potentially worsening side effects or reducing their effectiveness.

It’s worth noting that the quality and purity of CBD products vary tremendously. Non-prescription CBD products lack strict regulatory oversight, leading to potential contamination or inaccurate labelling, which might impact their effectiveness and safety.

CBD oil and medication interactions

Beyond CBD’s direct effects on brain chemistry, another significant concern lies in how it interacts with other medications. Many people don’t realise that CBD can alter how drugs work in their bodies, potentially affecting their mental health treatment.

How CBD affects medication processing

The liver contains enzymes called cytochrome P450 (CYP450) that break down most medications in your body. CBD both uses and blocks these same enzymes, creating what scientists describe as a biological bottleneck when taken with other drugs.

CBD particularly affects enzymes CYP2C19, CYP2D6, and CYP2C9. When CBD competes for these enzymes, other medications can’t be processed properly, leading to too much or too little drug in your system. This altered concentration can prevent medications from working correctly or increase the risk of side effects.

CYP3A4—which CBD also interferes with—is responsible for breaking down approximately 60% of all prescribed medications. This isn’t a minor concern; it affects most pharmaceutical treatments people take.

Interactions with depression medications

For people taking antidepressants, these interactions become particularly worrying. CBD inhibits the enzyme CYP2D6, which can increase blood levels of several common depression medications.

CBD can affect how your body processes popular antidepressants including:

• Sertraline (Zoloft)
• Fluoxetine (Prozac)
• Mirtazapine (Remeron)
• Citalopram (Celexa)
• Escitalopram (Lexapro)

CBD also interacts with monoamine oxidase inhibitors (MAOIs) such as tranylcypromine, phenelzine, and isocarboxazid. It can cause these medications to remain in your system longer, potentially leading to unpleasant side effects.

Some research suggests CBD might work together with certain antidepressants. One study found that small doses of both CBD and the antidepressant desipramine produced significant effects when given together. However, this interaction might not always be beneficial—it could make side effects worse or create unpredictable results.

Other medication risks

The consequences extend beyond depression medications. Researchers have identified 139 medications that cannabinoids might affect, with 57 medications where altered levels could be dangerous.

A useful guideline is the “grapefruit rule”: if your medication comes with a grapefruit warning, it’s likely to interact with CBD. This is because grapefruit and CBD block the same liver enzymes.

CBD can interact with common medications including:

• Warfarin (blood thinner)
• Amiodarone (heart rhythm medication)
• Levothyroxine (thyroid medication)
• Several seizure medications like clobazam, lamotrigine, and valproate

These interactions could worsen depression indirectly by causing side effects, treatment failures, or complications from other health conditions. The risk is particularly high for older adults, who often take multiple medications and process drugs differently.

If you’re taking any medications and considering CBD oil, you should speak to your GP or healthcare professional first to ensure it’s safe for you.

It’s worth noting that many over-the-counter CBD products contain inconsistent amounts of active compounds, unlike regulated medications. This variability makes interactions even less predictable and potentially more dangerous.

CBD product quality and THC contamination

The quality of CBD products sold in shops represents a significant concern that many consumers overlook. People often assume that what’s stated on the label matches what’s actually in the bottle—a potentially dangerous assumption that could impact mental health outcomes.

Inconsistent CBD concentrations in over-the-counter products

Laboratory testing reveals that many CBD products fail to contain the advertised amount of CBD. One analysis found that only 5 out of 63 products (8%) had measured CBD concentrations within 10% of their advertised amounts. Most products contained significantly less CBD than claimed, with aqueous tinctures averaging 25.7 mg/mL below advertised concentrations.

This inconsistency varies by product type. Among 21 CBD beverages examined in one study, only one was accurately labelled, with 78% containing less CBD than advertised. Oil-based products performed somewhat better, with roughly one-third properly labelled.

For someone using CBD to manage depression, these inconsistencies create serious problems:

• Unpredictable therapeutic effects
• Difficulty establishing effective dosing
• Financial frustration from spending considerable money on ineffective products

The FDA has repeatedly warned about these issues, having tested numerous CBD products and found many “did not contain the levels of CBD they claimed”.

THC contamination and its effects

Perhaps more concerning than inconsistent CBD levels is the widespread presence of undisclosed THC in many CBD products. Among 80 unregulated CBD products tested, 64% contained detectable levels of THC, ranging from 0.008 mg/mL to 2.071 mg/mL.

Even products specifically labelled as “THC-Free” often contain significant THC amounts. In one analysis, 5 out of 21 products (24%) marketed as “THC-Free” contained THC ranging from 0.015 mg/mL to 0.656 mg/mL.

The presence of unexpected THC can trigger anxiety, paranoia, and depression-like symptoms. With standard recommended dosing of 1-3 mL daily, someone might unknowingly consume up to 6.213 mg of THC daily when using a high-concentration product.

This unintentional exposure has led to serious consequences. The American Association of Poison Control Centres reported 4,680 CBD-related poisoning cases in 2021—more than double the 2,226 cases in 2020.

How poor-quality CBD may worsen depression symptoms

Poor-quality CBD products may exacerbate depression symptoms through several mechanisms. The unreliable composition makes consistent dosing impossible. As research suggests, CBD appears to have biphasic effects—low doses may help depression whilst high doses might worsen it.

THC contamination introduces psychoactive effects that can directly trigger or intensify depressive symptoms. THC has been linked to cognitive impairment, aggression, behaviour changes, paranoia, depression, and anxiety.

Without medical oversight, users typically self-adjust dosing based on perceived effects. If a product suddenly contains different concentrations of active compounds, this self-adjustment becomes dangerous, potentially worsening mental health outcomes.

The FDA has expressed concern that misleading claims and inconsistent product quality may lead consumers to “put off getting important medical care, such as proper diagnosis, treatment, and supportive care”. For depression—a potentially life-threatening condition—this delay could have serious consequences.

If you’re considering using CBD oil for depression, you should speak to your GP or other healthcare professional to ensure that it is safe and appropriate for you to do so.

Self-medicating with CBD: a concerning trend

People are increasingly turning to CBD oil as a self-prescribed solution for depression, despite limited scientific evidence supporting this approach. This trend towards self-medication presents significant risks that many users fail to consider.

Why do people choose CBD for depression?

The appeal of natural remedies draws many individuals towards CBD products. Growing numbers of people with depression are exploring CBD as an alternative to conventional treatments, reflecting a broader interest in natural approaches to mental health.

Online promotion plays a crucial role in this trend. CBD has gained widespread popularity on the internet as a supposed solution for mental health problems. Social media platforms amplify these claims, with dedicated groups sharing experiences about using CBD for mental health—often featuring advice from individuals without medical training.

Many people find CBD attractive because they perceive it has fewer side effects than prescription medications. Surveys indicate that 88% of users would prefer taking CBD over a prescription drug from a psychiatrist. This preference stems partly from concerns about the adverse effects of traditional antidepressants.

The absence of medical oversight

Most CBD users make treatment decisions without professional guidance. Only 19% of CBD users consult their doctor or pharmacist about taking CBD. Even among psychiatric patients, just 49% inform their psychiatrist about using the compound.

This lack of medical supervision creates several serious problems:

1. Unknown drug interactions with existing medications
2. Inappropriate dosing without clinical guidance
3. Delayed proper treatment for serious conditions
4. No ongoing monitoring for adverse effects

The reasons for avoiding medical consultation include lack of information (52.85%), perceived complexity of accessing treatment (39.86%), and difficulty finding cannabis clinics (23.23%). However, 80.47% of users in one study expressed a desire for healthcare professional advice about their cannabis use—highlighting a significant gap in current healthcare provision.

What do surveys reveal about self-treatment?

Survey data presents mixed results about self-treatment outcomes. In one Polish study, 86% of respondents reported feeling better after CBD treatment. Similarly, 53% claimed CBD definitely helped them, with another 33% saying it probably helped their depression symptoms.

Regarding adverse effects, 93% of respondents reported no negative effects from CBD use. Among those who experienced problems, issues included anxiety disorders, depressed mood, addiction, diarrhoea, and dry mouth.

However, these self-reported outcomes must be viewed with caution. Self-selection bias affects these results, as people choosing to participate in CBD surveys likely have positive expectations. Without standardised dosing or verified product quality, these results may not reflect typical experiences.

If you’re considering using CBD for depression, you should speak to your GP or other healthcare professional to ensure that it is safe and appropriate for you to do so.

The risks of self-medication extend beyond inconsistent results. As researchers note, “Self-medication with cannabis could present some risks for users. Main concerns include possible intoxication for non-standardised or high cannabis dosage and users experiencing known and unknown adverse events.”

It’s worth noting that whilst many users report positive experiences when self-medicating depression with CBD, the absence of medical oversight creates considerable risks—particularly considering that CBD can potentially worsen depression symptoms in some individuals.

Is CBD oil safe for everyone?

Certain groups face heightened risks when using CBD products, regardless of quality or dosage. These individuals should exercise particular caution or avoid CBD entirely to prevent worsening depression symptoms or other serious health complications.

People with bipolar disorder or psychosis

Research reveals a complex relationship between bipolar disorder and cannabinoids. Approximately 64% of people with bipolar disorder use cannabis during their lifetime, compared to only 34% in the general population. However, this high usage rate doesn’t translate to positive outcomes. Studies consistently show that cannabis use among bipolar patients leads to longer mood episodes, increased cycling, lower remission rates, and heightened suicide risk.

CBD alone has shown limited effectiveness for bipolar disorder in clinical settings. One case study examined two bipolar I patients hospitalised for manic episodes with psychotic symptoms. The first patient initially received CBD plus olanzapine, but once olanzapine was withdrawn, CBD alone failed to maintain improvements. The second patient received CBD monotherapy with no symptom improvement at any dose (600-1200 mg/day).

The medical consensus remains clear—cannabis (including CBD) often exacerbates the course of bipolar disorder and may trigger episodes of abnormal mood by disrupting brain chemistry that regulates mood.

Those taking multiple medications

CBD’s interaction with medications poses substantial risks through its inhibition of cytochrome P450 enzymes. This system metabolises approximately 60% of clinically prescribed medications. When CBD competes for these enzymes, it can dramatically alter drug metabolism, potentially leading to harmful concentrations in the bloodstream.

Several medication classes warrant special attention:

• Anticoagulants (blood thinners)
• Antiseizure medications
• Immunosuppressants
• Antiarrhythmics (heart rhythm medications)
• Antidepressants
• Antipsychotics

CBD increases drowsiness when combined with antihistamines, benzodiazepines, antipsychotics, antidepressants, opioids, alcohol, and supplements like kava, melatonin, and St. John’s Wort.

It’s worth noting that older adults require extra caution as they often take multiple medications and process drugs differently due to age-related physiological changes.

Individuals with liver or kidney issues

CBD presents specific concerns for those with compromised liver function. Although serious liver damage appears rare, CBD can cause dose-dependent hepatotoxicity. Higher doses (exceeding 300 mg daily) present greater risk, with studies showing potential for drug-induced liver injury.

Liver injury patterns associated with CBD include cholestatic and mixed patterns based on alanine aminotransferase and alkaline phosphatase ratios. Using CBD alongside medications known to cause liver damage (including leflunomide, lomitapide, mipomersen, pexidartinib, teriflunomide, and valproate) compounds this risk.

The FDA specifically warns that “users with impaired liver function are at higher risk to experience toxic effects than healthy individuals”. Those with pre-existing liver or kidney conditions should consult healthcare providers before using any CBD products.

What to do if you feel worse after taking CBD

If you’ve tried CBD oil for depression and found yourself feeling worse, immediate action is important to protect your mental health.

Recognising worsening symptoms

Watch for signs that your depression symptoms have intensified after taking CBD oil. These may include persistent sadness, hopelessness, irritability, loss of interest in activities, fatigue, or changes in sleep and appetite . Pay particular attention to any new or stronger thoughts of death or suicide, as these are serious warning signs requiring immediate attention .

The FDA-approved form of CBD (Epidiolex) lists depression and suicidal ideation as possible adverse reactions, with clinical trials showing increased risk of suicidal thoughts in 1 out of every 530 patients .

When to stop and seek help

Stop using CBD oil immediately if you notice worsening depression symptoms. Contact emergency services or go to the nearest accident and emergency department if you’re experiencing severe symptoms like difficulty breathing, unconsciousness, or seizures . For concerning reactions that aren’t immediately life-threatening, contact NHS 111 or speak to your GP .

Remember that toxic effects can occur even with small doses, depending on individual sensitivity .

Treatment alternatives to consider

If you’re considering using CBD oil for depression, you should speak to your GP or other healthcare professional to ensure that it is safe and appropriate for you to do so.

The National Institute for Health and Care Excellence (NICE) recommends several evidence-based approaches for depression, including:

• Cognitive behavioural therapy and other talking therapies
• Mindfulness and meditation practices
• Physical activity and exercise programmes
• Social activities and support groups

For more severe depression, your GP may recommend antidepressant medications that have undergone rigorous clinical trials and regulatory approval .

It’s worth noting that proper diagnosis and ongoing monitoring remain essential for managing depression effectively.

Conclusion

The relationship between CBD oil and depression is far more complex than many marketing claims suggest. Evidence from animal studies shows potential benefits, yet human research remains limited with significant gaps. What’s particularly concerning is that CBD oil can potentially worsen depression symptoms in some people.

The FDA-approved form of CBD, Epidiolex, lists depression and suicidal ideation among its possible adverse reactions. This serves as an important reminder that CBD affects brain chemistry in ways we don’t fully understand. People with bipolar disorder, those taking multiple medications, and individuals with liver problems face heightened risks.

Product quality adds another layer of concern. Many over-the-counter CBD products contain inconsistent concentrations or unexpected THC contamination, which can trigger anxiety and worsen mood symptoms. Without proper regulation, consumers cannot be certain what they’re actually taking.

If you’re considering using CBD oil for depression, you should speak to your GP or other healthcare professional to ensure that it is safe and appropriate for you to do so. This is particularly important if you’re taking any medications or have existing mental health conditions.

Anyone who feels worse after taking CBD should stop using it immediately and seek professional help. Depression requires proper medical care, and delaying appropriate treatment can have serious consequences.

Evidence-based treatments for depression include talking therapies, prescribed medications when appropriate, and lifestyle approaches like exercise and mindfulness practices. These treatments have been thoroughly researched and shown to be effective under medical supervision.

The current research into CBD and depression shows promise in some areas, yet significant limitations remain. Until we have more robust human studies, caution is essential when considering CBD for mental health conditions.

If you’re experiencing depression or have concerns about your mental health, please contact your GP or a mental health professional. This article is provided for general information only and should not replace professional medical advice.