A single 30 mg dose of CBD raised amitriptyline blood concentrations by 13%, suggesting CBD can interfere with drug metabolism even at doses far below therapeutic epilepsy levels.
Pharmacists, prescribers of tricyclic antidepressants, CBD users taking prescription medications
What the researchers found
In a crossover study of 12 healthy volunteers, a single 30 mg CBD dose taken one hour before amitriptyline significantly increased amitriptyline's AUC by 13% and peak concentration by 17%. CBD did not significantly affect tramadol or its active metabolite. The researchers note that chronic CBD dosing and taking CBD with food could amplify these interactions.
Why it matters
Most drug interaction studies use high CBD doses (300-1500 mg). This study shows that even a 30 mg dose, common in over-the-counter products, can meaningfully alter drug metabolism. For patients taking amitriptyline, this interaction could affect drug safety and efficacy.
The numbers in context
30 mg CBD dose; amitriptyline AUC increased 13% (95% CI: 1-26%, p=0.033); amitriptyline Cmax increased 17% (95% CI: 1-36%, p=0.041); 12 completers (4 male, 8 female); no significant effect on tramadol
How the study worked
Open-label, fixed-sequence, two-way crossover study in 13 healthy participants (12 completed). On Day 1, participants received amitriptyline and tramadol alone. After a 7-day washout, they received 30 mg CBD one hour before the same drugs. Blood samples collected over 24 hours. AUCs compared using mixed-effects models.
What this study cannot tell us
Single-dose study; chronic dosing likely produces larger interactions. Small sample size. Open-label design. Only tested in fasted conditions; CBD absorption increases substantially with food. Healthy volunteers may differ from patient populations.
How to read the evidence
Moderate: controlled crossover design with pharmacokinetic endpoints, but small sample, single dose, and open-label.
When this study was published
2025 publication
The bigger picture
CBD products are widely available and often used alongside prescription medications without medical supervision. This study adds to growing evidence that CBD can alter the metabolism of commonly prescribed drugs, even at low consumer-grade doses.
Questions still open
- How much larger would this interaction be with chronic CBD use or when taken with food?
- Should product labels for OTC CBD warn about potential drug interactions?
Read the original research
Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study.
British journal of clinical pharmacology
Citation
Gorbenko, Andriy A; Post, Titiaan E; Strugala, Pamela K; Klaassen, Erica S; Klumpers, Linda E; de Visser, Saco J; Sempio, Cristina; Klawitter, Jost; Heuberger, Jules A A C; Groeneveld, Geert J. (2025). Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study.. British journal of clinical pharmacology. https://doi.org/10.1002/bcp.70415
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