CBD Raised Citalopram Blood Levels by 50% in Anxiety Patients — a Drug Interaction That Needs Attention | Research

The takeaway

In 6 patients on stable SSRI doses, adding CBD (200-800 mg/day) increased citalopram blood levels by about 50% through CYP enzyme inhibition — a clinically significant interaction.

Anyone taking an SSRI for anxiety who is also using or considering CBD products.

~50%
Increase in citalopram blood levels when CBD was added at 200-800 mg/day

What the researchers found

This study combined lab work and real patient data to examine whether CBD interacts with common antidepressants. In vitro, CBD inhibited the metabolism of citalopram and, to a lesser extent, other SSRIs by blocking CYP enzymes.

The in vivo confirmation was more concerning. In 6 patients with anxiety disorders who were on stable citalopram or escitalopram doses, adding CBD at doses of 200-800 mg/day increased citalopram blood levels by approximately 50%. That's a substantial increase — enough to potentially cause side effects like serotonin syndrome symptoms, QT prolongation, or increased sedation.

The interaction was dose-dependent: higher CBD doses produced larger increases in SSRI blood levels. CBD minimally affected sertraline and mirtazapine metabolism in vitro, suggesting the interaction is somewhat SSRI-specific rather than universal across antidepressants.

Why it matters

CBD is increasingly marketed for anxiety, and many people taking it for anxiety are already on SSRIs. This study showed that combination isn't pharmacologically neutral. A 50% increase in SSRI blood levels is the kind of change that turns a therapeutic dose into a potentially problematic one.

This is especially important because CBD products are widely available without prescription, and most users don't consult a physician before combining them with their medications. The doses in this study (200-800 mg) are available in commercial CBD products.

The numbers in context

• CBD increased citalopram blood levels by ~50% in 6 patients

• CBD doses tested: 200-800 mg/day (ascending over 12 weeks)

• Citalopram and escitalopram most affected; sertraline and mirtazapine minimally affected

• Interaction mechanism: CYP enzyme inhibition (primarily CYP3A4, CYP2C19)

How the study worked

Two-part study. In vitro: tested CBD's inhibitory effects on CYP450-mediated metabolism of fluoxetine, sertraline, citalopram, and mirtazapine using human liver microsomes. In vivo: measured citalopram/escitalopram plasma levels in 6 anxiety disorder patients receiving ascending CBD doses (200-800 mg/day) over 12 weeks in a clinical trial setting.

Who was studied

N=6 young adults with anxiety disorders, receiving citalopram or escitalopram.

What this study cannot tell us

Only 6 patients in the clinical component — very small sample. Only citalopram/escitalopram tested in vivo. The CBD doses (200-800 mg) are higher than many commercial products but available. In vitro results may not perfectly predict in vivo interactions. No control group in the clinical arm.

How to read the evidence

Combined in vitro and small clinical study (n=6). Strong mechanistic evidence with human confirmation, but very small patient sample.

When this study was published

Published in 2021. CBD-SSRI interactions remain underappreciated in clinical practice.

The bigger picture

This study, alongside RTHC-00059 and RTHC-00070, continues building the case that cannabinoids are pharmacologically active in ways that matter for anyone taking other medications. The anxiety context makes it particularly relevant: the very population most likely to try CBD (anxious people) is the same population most likely to already be on SSRIs.

Replication

Not stated in abstract.

Funding

Not reported in abstract.

Conflicts of interest

Not reported in abstract.

Questions still open

Should CBD products carry warnings about SSRI interactions?
At what CBD dose does the interaction become clinically significant?
Are there safer antidepressant-CBD combinations than others?

Common questions

Can I take CBD with my antidepressant?

This study found CBD increased citalopram blood levels by about 50%. If you're on citalopram or escitalopram, adding CBD could effectively increase your SSRI dose. Talk to your doctor first.

Does this apply to all antidepressants?

Not equally. Citalopram was most affected. Sertraline and mirtazapine were minimally affected in lab tests. But the safest approach is to discuss any CBD use with your prescriber.

Read the original research

Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People.

Journal of clinical psychopharmacology, 41(5), 525-533

The Journal of Clinical Psychopharmacology is a reputable source focusing on the clinical aspects of psychopharmacology.

View on PubMed ↗Publisher’s paper ↗

Citation

Anderson, Lyndsey L; Doohan, Peter T; Oldfield, Lachlan; Kevin, Richard C; Arnold, Jonathon C; Berger, Maximus; Amminger, G Paul; McGregor, Iain S. (2021). Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People.. Journal of clinical psychopharmacology, 41(5), 525-533. https://doi.org/10.1097/JCP.0000000000001427