CBD and Antidepressants (SSRIs, SNRIs, TCAs)
David ReichUpdated:Key points at a glance:
CBD may influence liver enzymes such as CYP3A4 and CYP2C19, and in some cases CYP2D6. This can affect the blood levels of certain antidepressants. Particular care is advised with tricyclic antidepressants and medicines that carry a grapefruit warning. Taking CBD and antidepressants 2 to 4 hours apart does not reliably avoid possible interactions. Be alert to signs such as tiredness, tremor, sweating or a racing heart. Any combination should always be discussed with a doctor. It is generally advisable to start with a low amount, increase gradually, and keep a record of any symptoms.
CBD is often used as a food supplement in the form of CBD oil and is generally considered to be well tolerated. But how does CBD interact with antidepressants such as SSRIs, SNRIs or TCAs? This article summarises the current state of knowledge on possible benefits, risks and practical considerations – to help you make informed decisions together with a healthcare professional.
Use our interaction check tool for an initial overview. It does not replace medical advice, but can help you prepare for a discussion with a healthcare professional.
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How CBD works: endocannabinoid system and CYP450
CBD interacts with the endocannabinoid system (ECS), which is involved in regulating processes such as mood, sleep and stress responses. CBD is also broken down in the liver and can inhibit enzymes in the cytochrome P450 (CYP) system – mainly CYP3A4 and CYP2C19, and to a lesser extent CYP2D6. Many antidepressants are metabolised by these same enzymes. If an enzyme is inhibited, the level of a medicine in the body can increase and side effects may become more frequent or more noticeable. This is particularly relevant for substances with a narrow therapeutic window (such as tricyclic antidepressants).
CBD can slow down CYP450 liver enzymes involved in drug metabolism. As a result, levels of some antidepressants may rise – so combinations should be approached cautiously and under medical supervision.
Classes of antidepressants and possible CBD interactions
Antidepressants mainly increase the availability of neurotransmitters such as serotonin and noradrenaline. The most commonly used classes include SSRIs, SNRIs and TCAs; other frequently prescribed agents include MAO inhibitors, bupropion, mirtazapine and trazodone. Because CBD can influence CYP450 liver enzymes, there is a potential for CBD drug interactions with many prescription antidepressants.
| Class | Examples | Main CYP | Possible effect of CBD | What to watch for |
|---|---|---|---|---|
| SSRI | Sertraline, fluoxetine, paroxetine, citalopram, escitalopram | CYP2C19, CYP2D6, CYP3A4 (depending on substance) | CBD mainly inhibits CYP3A4/CYP2C19 → potentially higher levels | More pronounced SSRI side effects: nausea, tremor, restlessness, sweating |
| SNRI | Duloxetine, venlafaxine, desvenlafaxine | CYP1A2, CYP2D6, CYP3A4 (depending on substance) | Possible: moderately increased levels, more tiredness/nausea | Monitor blood pressure/heart rate, restlessness or sweating |
| TCA | Amitriptyline, nortriptyline, imipramine | CYP2D6, CYP2C19 | Higher risk due to narrow therapeutic window | Sedation, drowsiness, palpitations, dizziness → close monitoring |
| MAO inhibitors | Tranylcypromine, moclobemide | Not primarily CYP (classical/functional inhibition of other pathways) | Limited data; theoretical caution due to possible additive effects | Strict medical supervision; watch for serotonin-related symptoms |
| Bupropion (NDRI) | Bupropion | CYP2B6 (substrate), strong CYP2D6 inhibitor | Complex interaction possible; CBD partly inhibits CYP2D6 | Restlessness, sleep disturbances, monitor blood pressure |
| Mirtazapine (NaSSA) | Mirtazapine | CYP3A4 (mainly), 2D6/1A2 | CBD→CYP3A4 inhibition may increase levels | Stronger sedation/increased appetite possible |
| Trazodone | Trazodone | CYP3A4 | Potential increase in levels due to CBD | Watch for drowsiness, dizziness, drop in blood pressure |
CBD and SSRIs (e.g. sertraline, fluoxetine, paroxetine)
SSRIs are often metabolised via CYP2C19, CYP2D6 and CYP3A4. CBD can inhibit in particular CYP3A4 and CYP2C19. In practice, it is advisable to pay attention to typical SSRI side effects (nausea, tremor, restlessness, sweating). With sertraline, CYP2C19 involvement is considered relevant; with fluoxetine and paroxetine, CYP2D6 plays a central role – interactions are also considered possible here.
CBD and SNRIs (e.g. duloxetine, venlafaxine)
Duloxetine is metabolised via CYP1A2/2D6, venlafaxine mainly via CYP2D6 (with some CYP3A4 involvement). CBD may indirectly contribute to higher levels. Monitor blood pressure, heart rate, restlessness or increased sweating.
CBD and TCAs (e.g. amitriptyline, nortriptyline)
TCAs have a narrower therapeutic window. Even moderate increases in levels may intensify side effects. Extra caution is therefore advised when using CBD; any dose adjustments and monitoring should be carried out under medical supervision.
Other antidepressants: MAO inhibitors, bupropion, mirtazapine, trazodone
- MAO inhibitors (e.g. tranylcypromine, moclobemide): Very limited data. Due to their mechanism of action, close medical supervision is recommended.
- Bupropion: Substrate of CYP2B6 and a strong CYP2D6 inhibitor. Combination with CBD may be metabolically complex – close monitoring is advisable.
- Mirtazapine: Mainly metabolised via CYP3A4 – CBD may contribute to stronger sedation.
- Trazodone: Also metabolised via CYP3A4 – drowsiness/dizziness are possible.
Risks, warning signs and monitoring
- Marked agitation, confusion, fever, muscle twitching, intense sweating (possible signs of serotonin syndrome)
- Chest pain, persistent palpitations/rapid heartbeat, fainting/syncope, severe drowsiness (especially with TCAs)
Common signs that levels of an antidepressant might be increased when CBD is used together can include:
- SSRI/SNRI: nausea, tremor, restlessness, increased sweating, sleep disturbances
- TCA: pronounced sedation, dizziness, drowsiness, pounding/rapid heartbeat
- General: increased tiredness, dizziness, drop in blood pressure
Important: Taking CBD and antidepressants at different times (for example 2–4 hours apart) does not reliably prevent CYP interactions, as CBD acts systemically and enzyme inhibition may last longer.
CBD and antidepressants can affect each other via liver enzymes such as CYP3A4 and CYP2C19. Watch for stronger or unusual side effects, and seek medical advice promptly if you notice concerning changes.
Product choice: full spectrum, broad spectrum or isolate?
When combining CBD and prescription medicines, product quality and composition become particularly important. Different CBD formulations (full spectrum, broad spectrum, isolate) may vary in their overall effect profile, although CBD itself remains the key active ingredient for most interactions.
| Product type | Description | Possible pros/cons | May suit |
|---|---|---|---|
| Full spectrum | CBD + other cannabinoids, terpenes, trace THC | “Entourage effect”; in sensitive individuals possibly more sedation | Experienced users who prefer the full plant spectrum |
| Broad spectrum | Like full spectrum, but without detectable THC | Good compromise; lower likelihood of THC‑related tiredness | Users who wish to avoid THC |
| Isolate | Pure CBD | Very consistent; no entourage effect | Beginners, sensitive users, those looking to keep interaction risks as low as possible |
- Quality check: recent lab reports/CoA for each batch, CBD/THC content, testing for heavy metals/pesticides, transparent manufacturer information.
- Further reading: Full spectrum & more – the basics
Who should be particularly cautious?
Certain groups are more likely to experience clinically relevant CBD interactions with antidepressants and other prescription medicines and therefore require extra care and medical supervision:
- Older adults (changed pharmacokinetics, frequent polypharmacy)
- Liver conditions (reduced enzyme activity)
- Polypharmacy (several medicines, especially with a “grapefruit warning”)
- Pregnancy/breastfeeding: only after discussion with a doctor
- Adolescents: only under medical supervision
Caution is needed if you take several medicines, have liver problems, are older, pregnant, breastfeeding, or if your antidepressant has a grapefruit warning. In these cases, medical supervision for any CBD use is especially important.
Talk to your doctor: practical checklist
To safely assess CBD and antidepressant interactions (for example CBD with sertraline, fluoxetine, citalopram, duloxetine, venlafaxine or amitriptyline), prepare for your appointment with clear information:
- List all antidepressants (name, dose, time of intake, duration)
- Document any previous side effects or intolerances
- Note other products: prescription, OTC, herbal (e.g. St John’s wort), and grapefruit consumption
- Describe the planned form of CBD (oil, capsule), intended amount, timing, and purpose (e.g. sleep, stress)
- Agree a monitoring plan: which symptoms to watch for, and when to report back
Tip: “Start low, go slow” – begin with a low amount and increase gradually. Keep a brief symptom diary (date, CBD amount, antidepressant, symptoms/intensity, anything noteworthy).
Before combining CBD oil with antidepressants, discuss your full medication list and health situation with a doctor, start with a low CBD amount, increase slowly, and track changes in symptoms and side effects.
How do antidepressants work in the body?
Antidepressants such as SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin–noradrenaline reuptake inhibitors) and TCAs (tricyclic antidepressants) increase the availability of neurotransmitters in the brain. This is associated with stabilising mood and drive in many patients.
Examples of antidepressants
- SSRIs: Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine)
- SNRIs: Effexor (venlafaxine), Cymbalta (duloxetine), Pristiq (desvenlafaxine)
- TCAs: amitriptyline, imipramine, nortriptyline
Interactions between CBD and antidepressants: what the research suggests
CBD can inhibit the activity of liver enzymes in the CYP450 system and thereby slow the breakdown of some antidepressants. This may lead to higher drug levels and more pronounced side effects. This is particularly relevant for substances with a narrow therapeutic window (such as TCAs). Evidence is still limited and often based on theoretical mechanisms, small studies or case reports, so clinical relevance may vary from person to person.
Read our article here about interactions between CBD and medicines
Disclaimer: This article is for information purposes only and does not replace medical advice. Do not change medicines or dosages without consulting your doctor. No claims are made regarding the treatment or cure of illnesses.