Buijs Sanne M, Braal C Louwrens, Buck Stefan A J, van Maanen Noud F, van der Meijden-Erkelens Lonneke M, Kuijper-Tissot van Patot Heleen A, Hoop Esther Oomen-de, Saes Lotte, van den Boogerd Sophia J, Struik Liesbeth E M, van Rossum-Schornagel Quirine C, Mathijssen Ron H J, Koolen Stijn L W, Jager Agnes
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Clinical Cannabis Care Pharmacy, Breukelen, the Netherlands.
NPJ Breast Cancer. 2023 Aug 5;9(1):63. doi: 10.1038/s41523-023-00570-x.
Tamoxifen may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Patients searching for relief are increasingly turning to cannabinoids such as CBD-oil. However, CBD-oil might affect tamoxifen pharmacokinetics (PK) through CYP2D6 inhibition. The aims of this open-label, single-arm study were (1) to determine the PK profile of tamoxifen when using CBD-oil, and (2) to subsequently investigate whether CBD-oil has a beneficial influence on side effects. Study patients had to have steady-state endoxifen concentrations ≥16 nM (conservative threshold). PK sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter. Bio-equivalence could be concluded if the 90% confidence interval (CI) for the difference in endoxifen AUC fell within the [-20%; +25%] interval. The effect of CBD-oil on side effects was evaluated using the FACT-ES questionnaire. Endoxifen AUC decreased after CBD-oil by 12.6% (n = 15, 90% CI -18.7%, -6.1%) but remained within bio-equivalence boundaries. The endocrine sub-scale of the FACT-ES improved clinically relevant with 6.7 points (n = 26, p < 0.001) and health-related quality of life improved with 4.7 points after using CBD (95% CI + 1.8, +7.6). We conclude that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects. Clinical trial registration: International Clinical Trial Registry Platform (NL8786; https://www.who.int/clinical-trials-registry-platform ).
他莫昔芬可能会导致令人烦恼的副作用，从而导致患者不依从并降低生活质量。寻求缓解的患者越来越多地转向使用大麻素类药物，如大麻二酚油（CBD油）。然而，CBD油可能通过抑制细胞色素P450 2D6（CYP2D6）影响他莫昔芬的药代动力学（PK）。这项开放标签、单臂研究的目的是：（1）确定使用CBD油时他莫昔芬的PK特征；（2）随后研究CBD油是否对副作用有有益影响。研究患者的稳态内美通浓度必须≥16 nM（保守阈值）。在开始使用CBD油时及之后28天进行PK采样和副作用评估。如果内美通曲线下面积（AUC）差异的90%置信区间（CI）落在[-20%；+25%]区间内，则可得出生物等效性结论。使用FACT-ES问卷评估CBD油对副作用的影响。使用CBD油后，内美通AUC下降了12.6%（n = 15，90% CI -18.7%，-6.1%），但仍在生物等效性范围内。FACT-ES的内分泌子量表在临床上有显著改善，提高了6.7分（n = 26，p < 0.001），使用CBD后健康相关生活质量提高了4.7分（95% CI +1.8，+7.6）。我们得出结论，对于因他莫昔芬相关副作用而使用CBD油的患者，如果其质量良好且剂量低于50 mg，则不必加以劝阻。临床试验注册：国际临床试验注册平台（NL8786；https://www.who.int/clinical-trials-registry-platform ）
