Can CBD be used with antidepressants?

Medicines and the importance of their interactions

From peer-reviewed publications and drug labels: the warnings, most important first. The same warnings also appear in the interaction checker. A medicine that is not listed can still interact with CBD.

How does the interaction happen?

Most antidepressants are broken down in the liver by enzymes called CYPs; which enzyme matters most depends on the medicine. Citalopram and escitalopram are broken down mainly by CYP2C19 and CYP3A4. CYP2C19 plays a role in the main breakdown pathway of sertraline, and for amitriptyline, too, it is mostly CYP2C19. For fluoxetine, paroxetine, venlafaxine and vortioxetine, the main pathway is CYP2D6; agomelatine is broken down about 90% by CYP1A2, bupropion by CYP2B6 and trazodone by CYP3A4. (Citalopram prescribing information §12.3, Escitalopram prescribing information §12.3, PMID 36627907, PMID 41398552, PMID 39719830, Venlafaxine prescribing information §12.3, Vortioxetine prescribing information §12.3, Agomelatine European prescribing information 4.5, FDA Epidiolex label §12.3 (05/2026), Trazodone prescribing information §12.3)

CBD slows some of these enzymes, but not all to the same degree. The US product information for approved CBD describes CBD as a moderate inhibitor of CYP2C19 and a weak inhibitor of CYP1A2. In a study in healthy volunteers with a CBD-dominant cannabis extract, the clearest slowing was seen in CYP2C19. The fact that the rise seen with citalopram resembles the rise seen with medicines that slow CYP2C19 fits this picture. (FDA Epidiolex label §7.2 (05/2026), PMID 37313955, PMID 41622700)

For medicines broken down by CYP2D6, the picture is less clear: CBD strongly slowed CYP2D6 in the laboratory, but in a study in healthy volunteers with a single dose of a CBD-dominant cannabis extract, this enzyme's activity did not change. In laboratory experiments, CBD had very little effect on the breakdown of fluoxetine, sertraline and mirtazapine. With bupropion, approved CBD did not raise blood levels; on the contrary, they fell by about 20%. According to the US product information, CBD can both slow and speed up CYP2B6, which breaks down bupropion, in the laboratory. (PMID 21821735, PMID 37313955, PMID 34121064, FDA Epidiolex label §12.3 (05/2026), EMA Epidyolex prescribing information 4.5)

The interaction may not be limited to blood levels. CBD itself can cause sleepiness, diarrhea and tiredness; the product information states that CBD can increase this effect together with other medicines that cause sleepiness and with alcohol. With antidepressants that themselves cause sleepiness, such as mirtazapine and trazodone, this added effect may become important. (EMA Epidyolex prescribing information 4.4 and 4.8, FDA Epidiolex label §5.2 and §7.4 (05/2026), Mirtazapine prescribing information §5.8, Trazodone prescribing information §5.9 and §7)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

1. Drug-level study

   Citalopram: level rose by 43% (2026)

   In a study run by the US Food and Drug Administration (FDA), 20 healthy volunteers took approved CBD at 2.5 mg/kg twice a day for 12 days; this dose was chosen to be close to the amounts used in nonprescription CBD products. With CBD, the total amount of a single dose of citalopram in the blood (AUC: total exposure over the time the medicine stays in the blood) rose by 43% and its peak level by 12%. The researchers write that the rise is similar to that seen with cimetidine, which is known to slow the breakdown of citalopram, and that whether it turns into side effects in patients needs to be studied separately.

   Source: PMID 41622700, ClinicalTrials.gov NCT06192589

2. Case series

   Citalopram and escitalopram: levels rose in 6 patients (2021)

   As part of a clinical study, CBD in increasing doses (200–800 mg a day) was added for 12 weeks in 6 young patients taking citalopram or escitalopram for an anxiety disorder. After CBD was added, blood citalopram levels rose significantly. In laboratory experiments in the same paper, CBD slowed the breakdown of citalopram and escitalopram by CYP2C19 and CYP3A4. The authors state that it is unclear whether side effects also increased.

   Source: PMID 34121064

3. Case report

   Sertraline: one case and two side-effect reports (2022–2024)

   A 78-year-old man who had taken 50 mg of sertraline a day for 20 years started taking a nonprescription CBD product every day for his pain. Over the following year, his blood sodium fell (lowest 120 mmol/L) and he developed short-term memory and attention problems; when first CBD and then sertraline were stopped, his sodium rose and his thinking skills recovered. Because of his genetic makeup, the CYP2C19 enzyme that breaks down sertraline worked slowly in this patient; the authors think CBD may have slowed this enzyme further, but sertraline blood levels were not reported. In the records of a side-effect monitoring center in Poland, diarrhea, vomiting, fever and severe tiredness were also reported in 2 people using CBD oil together with sertraline; these people were also taking other medicines. In the laboratory, however, CBD had very little effect on sertraline's breakdown; in other words, how the interaction happens is not clear.

   Source: PMID 36627907, PMID 39502532, PMID 34121064

4. Drug-level study

   Amitriptyline: level rose by 13% after a single dose (2026)

   In a study of 13 healthy volunteers, a single 30 mg dose of CBD oil was given on an empty stomach 1 hour before amitriptyline. CBD raised the total amount of amitriptyline in the blood by 13% and its peak level by 17%; the active breakdown product nortriptyline and tramadol given at the same time did not change. The authors state that the effect may be larger when CBD is used continuously or taken with food.

   Source: PMID 41398552

5. Case report

   Fluoxetine: symptoms worsened in a teenager (2022)

   In a 17-year-old taking fluoxetine, worsening of insomnia, restlessness, hyperactivity and obsessive-compulsive disorder symptoms was reported after CBD oil was added; the complaints eased when CBD was stopped. The authors interpreted this as a possible interaction between CBD, fluoxetine and the patient's CYP2D6 gene. A review of cases in children and teenagers rated the interaction as probable; however, the patient had had similar symptoms before, and since CYP2D6 was not slowed in a human study with a single dose of a CBD-dominant cannabis extract, the cause is unclear. The child case reported with paroxetine involved smoked marijuana, not CBD.

   Source: PMID 35652796, PMID 39719830, PMID 37313955

6. Drug-level study

   Bupropion: level fell by about 20%

   When given with approved CBD (7.5 mg/kg twice a day), the blood level of a single dose of bupropion fell by about 20%; bupropion's active breakdown product formed by CYP2B6 (hydroxybupropion) did not change. The European product information considers this difference to be within normal variation and not clinically meaningful. The US product information describes CBD as both an inducer and an inhibitor of CYP2B6. The effect of higher CBD doses is not known; the US product information recommends considering a change in the dose of medicines broken down by CYP2B6 at these doses if needed.

   Source: EMA Epidyolex prescribing information 4.5, FDA Epidiolex label §7.2 and §12.3 (05/2026)

7. Drug-level study

   Agomelatine: no direct study; same enzyme pathway

   There is no study looking at agomelatine together with CBD. Agomelatine is broken down about 90% by CYP1A2; it is not used with medicines that strongly slow this enzyme, and caution is advised with those that moderately slow it. Approved CBD (750 mg twice a day) raised the total amount in the blood of caffeine, which is broken down by the same pathway, by 95%; this is why the product information classes CBD as a weak inhibitor of CYP1A2. In addition, both agomelatine and CBD can raise liver enzymes.

   Source: Agomelatine European prescribing information 4.4 and 4.5, PMID 33951339, FDA Epidiolex label §5.1 and §7.2 (05/2026), EMA Epidyolex prescribing information 4.5

8. Laboratory study

   Trazodone, mirtazapine, vortioxetine, SNRIs and other tricyclics: no human data

   No human study looking at these medicines together with CBD could be found. In the laboratory, CBD had very little effect on mirtazapine's breakdown. For CYP3A4, which breaks down trazodone, the data conflict: approved CBD (750 mg twice a day) did not change the level of midazolam, which is broken down by the same pathway, while a single dose of a CBD-dominant cannabis extract raised midazolam by 56%. Vortioxetine and venlafaxine are mostly broken down by CYP2D6; CBD slowed this enzyme in the laboratory, but did not slow it in a study in healthy volunteers with a single dose of a CBD-dominant cannabis extract. In a systematic review, all the interaction cases found with tricyclic antidepressants involved smoked marijuana, not CBD; there are no CBD-specific data for tricyclics other than amitriptyline.

   Source: PMID 34121064, FDA Epidiolex label §12.3 (05/2026), PMID 37313955, PMID 21821735, Vortioxetine prescribing information §12.3, Venlafaxine prescribing information §12.3, PMID 38868665

9. Case report

   Side effects reported with cannabis containing THC

   In side-effect records of patients using medical cannabis with a high THC content (18–22%), severe reactions up to loss of consciousness were reported with sertraline, inflammation of the pancreas with mirtazapine, and confusion and excessive sleepiness with trazodone. In teenagers who smoked marijuana and took tricyclic antidepressants, symptoms suggesting tricyclic poisoning, such as palpitations, confusion and hallucinations (seeing things), were also seen. These findings relate to cannabis containing THC, not to CBD.

   Source: PMID 39502532, PMID 38868665

10. Official drug information

    Product information for approved CBD

    Antidepressants are not named in the US (Epidiolex, 05/2026) or European (Epidyolex) product information. The US product information recommends considering a dose reduction if needed for medicines broken down by CYP2C19; the European product information makes the same recommendation for medicines broken down by CYP2C19 or with a narrow safe range. Both state that CBD can increase sleepiness together with other medicines that cause sleepiness and with alcohol.

    Source: FDA Epidiolex label §5.2 and §7.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5

What is monitored?

• More side effects: if you notice that your antidepressant's side effects increase after starting CBD or increasing the amount, tell your doctor. According to citalopram's product information, side effects such as tiredness, insomnia, sweating and sleepiness increase with the dose. (Citalopram prescribing information §6.1, PMID 41622700)
• Heart rhythm: if you take citalopram, tell your doctor right away about symptoms that may be related to heart rhythm, such as palpitations, dizziness or fainting. The product information states that this risk increases with medicines that slow citalopram's breakdown. (Citalopram prescribing information §5.2 and §7)
• Signs of low sodium: SSRIs can lower blood sodium, especially in older people. If you notice headache, difficulty concentrating, forgetfulness, confusion, weakness or unsteadiness, let your doctor know. (Citalopram prescribing information §5.9, PMID 36627907)
• Changes in your mood: the US product information for approved CBD states that, like other epilepsy medicines, CBD may increase the risk of suicidal thoughts and behavior in a small number of people, and asks that attention be paid to new or worsening depression and to unusual changes in mood or behavior. If you notice such a change, tell your doctor right away. (FDA Epidiolex label §5.3 and §17 (05/2026), EMA Epidyolex prescribing information 4.4)
• Sleepiness and driving: if you use CBD together with an antidepressant that causes sleepiness, such as mirtazapine or trazodone, do not drive or operate machinery until you know how it affects you. (FDA Epidiolex label §5.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.7, Trazodone prescribing information §5.9) CBD and driving
• Liver tests: people taking agomelatine already have liver tests at regular intervals; because CBD can also raise liver enzymes, it is important that your doctor knows you use CBD. (Agomelatine European prescribing information 4.2 and 4.4, FDA Epidiolex label §5.1 (05/2026))

Frequently asked questions

References

Last reviewed: October 27, 2026. On this date, each source was opened and checked against the related sentence.