CBD Raised Citalopram Blood Levels by 50% in Anxiety Patients — a Drug Interaction That Needs Attention
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.
Quick Facts
What This Study 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.
Key Numbers
- 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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- ~50% Increase in citalopram blood levels when CBD was added at 200-800 mg/day
- Evidence Grade:
- Combined in vitro and small clinical study (n=6). Strong mechanistic evidence with human confirmation, but very small patient sample.
- Study Age:
- Published in 2021. CBD-SSRI interactions remain underappreciated in clinical practice.
- Original Title:
- Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People.
- Published In:
- Journal of clinical psychopharmacology, 41(5), 525-533 (2021) — The Journal of Clinical Psychopharmacology is a reputable source focusing on the clinical aspects of psychopharmacology.
- Authors:
- Anderson, Lyndsey L(10), Doohan, Peter T(7), Oldfield, Lachlan, Kevin, Richard C, Arnold, Jonathon C, Berger, Maximus, Amminger, G Paul, McGregor, Iain S
- Database ID:
- RTHC-02967
Evidence Hierarchy
Watches what happens naturally without intervening.
What do these levels mean? →Frequently Asked 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.
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Cite This Study
https://rethinkthc.com/research/RTHC-02967APA
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
MLA
Anderson, Lyndsey L, et al. "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, 2021. https://doi.org/10.1097/JCP.0000000000001427
RethinkTHC
RethinkTHC Research Database. "Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of..." RTHC-02967. Retrieved from https://rethinkthc.com/research/anderson-2021-citalopram-and-cannabidiol-in
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.