CBD Oil Shows Modest Improvements in Tamoxifen-Related Adverse Effects

Patients experiencing tamoxifen-related side effects may benefit from cannabidiol (CBD) oil, according to a poster presentation from the 2022 San Antonio Breast Cancer Symposium.

CBD led to decreases in several tamoxifen-related adverse effects (AEs). Without CBD, the percentage of patients (n = 26) who experienced grade 1 or 2 insomnia was 62% (n = 16) and 38% (n = 10), respectively. With CBD, the rates of grade 1 or 2 insomnia were 73% (n = 19) and 12% (n = 3). Similarly, with for hot flashes, tamoxifen alone induced grade 1 and grade 2 symptoms in 77% (n = 20) and 19% (n = 5) of patients, respectively, whereas the addition of CBD yielded grade 1 and 2 symptoms in 85% (n = 22) and 4% (n = 1) of the population.

Without CBD, the rates of arthralgia were 58% (n = 15) and 38% (n = 10), respectively. Following CBD, these rates were 81% (n = 21) and 12% (n = 3). The rate of grade 1 mood alterations decreased from 73% (n = 19) to 65% (n = 17) following CBD, and the rate of grade 2 mood alterations remained at 4% (n = 1). Similarly, with no CBD, the rate of grade 1 muscle cramps was 27% (n = 7) and the grade 2 rate was 4% (n = 1). Following CBD, no patients reported grade 2 muscle cramps and the rate of grade 1 muscle cramps was 31% (n = 8).

The rate of headache was consistent across the 2 groups: 4 patients (15%) experienced grade 1 headaches both with and without CBD. Vaginal dryness decreased from 2 patients (8%) and 1 (4%) patient with grade 1 or 2 severity without CBD, to 1 patient (4%) with grade 1 severity with CBD. Four patients (15%) and 2 patients (8%) experienced grade 1 amnesia without and without CBD, respectively. Where 2 patients (8%) experienced weight gain with tamoxifen alone, 1 patient (4%) did so with CBD.

Moreover, the mean heath related quality-of-life (HR-QOL) without CBD was 74.3 and the mean after 4 weeks of CBD was 79.0, translating to a 4.7-point increase in HR-QOL (95% CI, 1.8-7.6; P = .003). In terms of endocrine symptoms, the mean without CBD was 47.1 and the mean after 4 weeks of CBD was 53.8. In this population, endocrine symptoms improved by 6.7 points (95% CI P < .001).

Tamoxifen is often associated with bothersome AEs, which may negatively effect a patient’s QOL, as well as treatment adherence, wrote study authors. Many patients seeking relief from these AEs have fixes their attention to cannabinoids such as cannabidiol (CBD), they continued; however, the effects of CBD on tamoxifen-related AEs have not been investigated. Moreover, because tamoxifen is mainly metabolized through CYP2D6, and CBD is suggested to be an in-vitro inhibitor of CYP2D6, the use of CBD might affect tamoxifen pharmacokinetics.

“The aims of this study were to determine the pharmacokinetic interaction between CBD and tamoxifen, and to subsequently investigate where there is a beneficial influence of CBD on tamoxifen-related [AEs] and [QOL],” Sanne Buijs, MD, of the Department of Medical Oncology, Erasmus MC Cancer Institute, and co-investigators wrote.

To that end, investigators enrolled patients with endoxifen levels of at least 16 nM and at least one tamoxifen-related AE, including hot flashes, arthralgia, mood alterations, and insomnia.

Median patient age was 49.5 years [range, 47-54], the median BMI was 26.1 [range, 24-31], and the median months of tamoxifen use was 13 [range, 5-24]. Thirteen patients (50%) had received local treatment with lumpectomy plus radiotherapy, 4 (15%) had received mastectomy alone, and 9 (35%) had received mastectomy plus radiotherapy. Twenty patients (77%) had undergone neoadjuvant chemotherapy and one patient (4%) had received neoadjuvant anti-HER2 therapy.

Of note, CBD led to toxicities in 38% of patients, all of which were categorizes as grade 1 in accordance with Common Terminology Criteria for Adverse Events guidelines.

With no CBD, 3 patients experienced grade 1 and grade 2 fatigue (12% for both). However, with CBD, 8 patients (31%) experienced grade 1 and 1 patients (4%) experienced grade 2 fatigue. No patients experienced dry mouth or nausea with tamoxifen alone, but these toxicities were reported by 3 (12%) and 2 (8%) of patients receiving CBD.

Study authors acknowledged that 4 weeks of CBD use was a short amount of time for a study, and that a longer study period may yield better insights on CBD and clinically relevant improvements in HR-QOL.

Investigators also noted that the combination of CBD and tamoxifen did lead to a significant decrease in endoxifen plasma concentrations, but this decrease remains within bio-equivalence boundaries and is not considered clinically relevant.

Reference

Buijs S, Braal CL, Buck SAJ, et al. CBD-oil: a potential solution in case of severe tamoxifen-related side effects. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. P1-02-08.