Even Low-Dose CBD Increased Blood Levels of the Antidepressant Amitriptyline

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.

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.

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.

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.

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.