CBD and fluoxetine (e.g. Prozac, Fluctin, Fluoxetin-ratiopharm)
David ReichUpdated:Key points at a glance:
When CBD is taken at the same time as fluoxetine, it may inhibit the liver enzymes CYP2C19, CYP3A4 and CYP2D6. Fluoxetine itself also inhibits CYP2D6 and has a long half-life. As a result, blood levels of one or both substances may increase and side effects such as tiredness, dizziness and nausea may become more likely. In rare cases, a serotonin syndrome has been reported in connection with combinations of medicines that influence serotonin levels. Any combination should only be started after medical advice, with a low dose and close monitoring. Other medicines should also be checked for possible CYP-related interactions.
If you are taking fluoxetine (an SSRI), CBD may influence drug levels via inhibition of liver enzymes (CYP450). The risk of tiredness, dizziness and, in rare cases, serotonin syndrome may be increased. Only consider CBD after medical advice, start with a low dose and ensure close monitoring.
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What are CBD and fluoxetine?
CBD in brief
Cannabidiol (CBD) is a non-intoxicating compound from the cannabis plant. It is being researched in relation to potential effects on areas such as anxiety, sleep and pain perception. Common, usually mild side effects include tiredness, dry mouth and gastrointestinal discomfort. Interactions with medicines are possible; always coordinate use with your healthcare team. Products are available in various forms, including CBD oil.
Fluoxetine in brief
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used for conditions such as depression and panic disorder. It increases the availability of serotonin in the synaptic cleft. Brand names include Prozac. Fluoxetine has a long duration of action and itself inhibits the enzyme CYP2D6.
CBD is non-intoxicating and may interact with prescription medicines via liver enzymes. Fluoxetine is an SSRI with a long half-life and strong CYP2D6 inhibition, so combining CBD and fluoxetine requires individual medical assessment and careful monitoring.
CBD and fluoxetine in comparison
| Criterion | CBD | Fluoxetine | Relevance for combination |
|---|---|---|---|
| Main metabolism (CYP) | Inhibits, among others, CYP2C19, CYP3A4, CYP2D6 | Metabolised via CYP2D6 (important), others also contribute; strongly inhibits CYP2D6 | Possible additive inhibition → slower metabolism of other substances |
| Half-life | Variable depending on dose/form; from hours to a few days | Fluoxetine approx. 2–4 days; active metabolite norfluoxetine approx. 7–15 days | Effects/interactions may occur with a delay and last longer |
| Common side effects | Tiredness, dry mouth, GI complaints | Nausea, sleep disturbances, dizziness, sexual dysfunction | Possible additive tiredness/dizziness |
| Serotonergic effect | No direct SSRI effect | Yes, increases serotonin in the CNS | Very rare serotonin syndrome; vigilance required |
How can CBD and fluoxetine interact?
CYP450 mechanism explained
CBD may inhibit enzymes of liver metabolism (cytochrome P450), in particular CYP2C19, CYP3A4 and CYP2D6. Fluoxetine is metabolised via CYP systems, with CYP2D6 playing an important role. Fluoxetine itself also strongly inhibits CYP2D6.
In combination, an additive inhibitory effect is therefore possible: the breakdown of fluoxetine, its active metabolite norfluoxetine and potentially other medicines taken at the same time may be slowed. This may increase drug levels or delay their decline.
What does this mean for levels and effects?
- Potentially higher or more prolonged concentrations of fluoxetine/norfluoxetine.
- Possibly more pronounced side effects, especially tiredness, dizziness, nausea and gastrointestinal discomfort.
- Delayed onset/offset: due to the long half-life of fluoxetine (2–4 days) and norfluoxetine (7–15 days), interactions may persist for days to weeks.
- Indirect risk: other CYP2D6/CYP3A4 substrates in your medication regimen may also be affected.
For further background on CBD–drug interaction mechanisms, see this overview of CBD–CYP450 interactions: CBD and CYP450: overview of drug interactions.
Both CBD and fluoxetine act on CYP450 liver enzymes (especially CYP2D6 and CYP3A4). When taken together, the metabolism of fluoxetine and other medicines can be slowed, so blood levels may stay higher for longer and side effects can become more noticeable.
Risks and side effects of the combination
Common side effects (additive)
- Tiredness, drowsiness, feeling dazed
- Dizziness, headaches, difficulty concentrating
- Gastrointestinal complaints (nausea, diarrhoea)
- Dry mouth, slight drop in blood pressure
Inform your healthcare team if new or more intense side effects occur – particularly in the first 2–4 weeks after starting CBD, when changing CBD dose, or after adjustments to your fluoxetine regimen.
Serotonin syndrome: warning signs and when to act
Serotonin syndrome is a rare but serious complication associated with serotonergic medicines such as fluoxetine. CBD is not an SSRI, but by affecting liver enzymes it may theoretically influence fluoxetine levels. Pay attention, particularly when starting treatment or changing doses, to:
- Marked inner restlessness, nervousness
- Tremor, increased reflexes, muscle twitching
- Heavy sweating, nausea/vomiting, diarrhoea
- Rapid heartbeat (increased heart rate), fluctuating blood pressure
- Confusion, agitation; possibly fever
Seek urgent medical assessment: If several of these symptoms appear for the first time or become significantly worse, seek medical help immediately. Do not increase any doses on your own initiative.
Practical use: how to proceed safely
Important safety note: This article does not replace medical advice. Never stop antidepressants on your own. Only start or change CBD in consultation with your doctor and inform your healthcare team about all prescription medicines, over-the-counter products and supplements you are using.
Before you start: checklist for your appointment
- List of all current medicines and food supplements (with doses), including “as needed” medication
- Known liver or kidney disease, heart rhythm disturbances, pregnancy/breastfeeding
- Planned purpose of CBD use (e.g. sleep, anxiety, pain) and preferred form (oil/capsules)
- Previous experience with fluoxetine (benefits, side effects, past dose changes)
- Planned approach: start low, go slow, realistic expectations, and a monitoring plan (what to watch for and when to review)
Monitoring in the first weeks: track your symptoms
- Time of day and dose for CBD and fluoxetine
- Mood, drive, sleep quality, inner restlessness
- Sedation/drowsiness, dizziness, headaches
- Gastrointestinal symptoms (nausea, diarrhoea, appetite)
- If possible: blood pressure/pulse (especially with dizziness or rapid heartbeat)
Review any changes over 2–4 weeks; discuss anything unusual with your healthcare team at an early stage.
Dosing schedule and lifestyle tips
- In agreement with your healthcare team, taking CBD and fluoxetine at different times (for example, several hours apart) may theoretically help to avoid peak concentrations.
- Consistently start low and adjust slowly start low, go slow. There is no universally applicable mg recommendation for CBD with fluoxetine.
- Avoid additional CYP inhibitors (e.g. grapefruit) unless discussed with your doctor, as they may further affect CBD metabolism and fluoxetine levels.
- Keep alcohol to a minimum, ensure adequate fluid intake, and avoid self-directed dose increases of either CBD or fluoxetine.
Interaction check: Select your medicine and CBD form below to explore potential interactions such as CYP3A4 and CYP2D6 inhibition. This does not replace an individual medical assessment.
💊 Medication Finder
We have analysed the interactions between CBD and 140 medications und Medikamentenarten analysiert. You can view the full overview here or use the search below to find your specific medication.
Who should be particularly cautious?
- People with liver disease
- Older adults (higher interaction and fall risk)
- Those on multiple medicines (polypharmacy), especially CYP2D6/CYP3A4 substrates
- Known heart rhythm disturbances or QT prolongation
- Pregnancy/breastfeeding (only after careful benefit–risk assessment)
- History of mania or hypomanic episodes
Evidence: what is known and what is not?
The available data on CBD in combination with SSRIs (including fluoxetine) is limited. There is a plausible pharmacological basis for interactions via CYP450 (for example CBD affecting CYP3A4 and CYP2D6), as well as individual case reports. Robust, controlled clinical studies on the specific combination of CBD and fluoxetine are currently scarce.
Official prescribing information describes strong CYP2D6 inhibition for fluoxetine; reviews describe CBD as an inhibitor of several CYP isoenzymes involved in medicine metabolism. Any conclusions about CBD–fluoxetine interactions should therefore be made cautiously and assessed on an individual basis.
There is a clear theoretical basis for CBD–fluoxetine interactions via liver enzymes, but only limited clinical data. Because of this uncertainty, the combination should be approached cautiously: involve your doctor, start with a low CBD dose if agreed, and monitor closely for changes in side effects or mood.
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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.