Estradiol Patch and Cannabis Interaction Profile

What do the patch labels say about interactions?

Climara and Vivelle-Dot both state that estrogens are metabolized partly by CYP3A4, so inducers or inhibitors of the enzyme may change estrogen plasma concentrations [1][2]. The labels name St. John's wort, phenobarbital, carbamazepine and rifampin as inducers that may reduce estrogen concentrations, with a possible loss of therapeutic effect or a change in the uterine bleeding pattern. They name erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice as inhibitors that may raise estrogen concentrations and may result in adverse reactions [1][2]. Cannabis is not named in the interaction section of either label, and neither label describes combining the patch with cannabis [1][2].

Does the patch route change any of this?

Transdermal estradiol avoids first-pass metabolism. The Climara label states that systemic availability of estradiol after transdermal use is about 20 times higher than after oral use [1].

What do the closest studies show?

A lab study of ovarian cells

In a human granulosa cell line (KGN), THC and CBD produced no significant change in basal or stimulated estradiol secretion and did not alter expression of CYP19A1, the gene for aromatase [4]. This is a cell-culture model of ovarian estradiol production, not of estradiol absorbed from a patch.

A trial of THC across the menstrual cycle

Sixty healthy women who were occasional cannabis users received oral THC 7.5 mg, THC 15 mg and placebo. They were tested during either the early follicular phase, when their own estradiol is low, or the late follicular phase, when it is higher. On a Go/No Go task, THC increased response time and errors of commission and reduced accuracy compared with placebo, and these impairments were not related to estradiol levels [3]. The estradiol in this trial was each woman's own cycle estradiol, not patch-delivered estradiol.

A cohort of men

In a cohort of young Swiss men, estradiol, anandamide, androgens and sex hormone binding globulin were higher in cannabis users, particularly chronic, recent and CBD-positive consumers [5]. That is endogenous estradiol in men.

Do estradiol and cannabinoids interact in the other direction?

A review by Craft and colleagues identifies estradiol as the gonadal hormone contributing most to sex differences in cannabinoid effects in adult rodents, while noting that the same has not yet been firmly established in humans [6]. A second review reports that female rodents are generally more sensitive to delta-9-THC, with ovarian hormones including estradiol and progesterone among the likely contributors [7].