Impaired inhibition after delta-9-tetrahydrocannabinol in women not related to circulating estradiol levels

Abstract

Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), impair cognitive processes, including the ability to inhibit inappropriate responses. However, responses to cannabinoid drugs vary widely, and little is known about the factors that influence the risk for adverse effects. One potential source of variation in response to cannabinoids in women is circulating ovarian hormones such as estradiol and progesterone. Whereas there is some evidence that estradiol affects responses to cannabinoids in rodents, little is known about such interactions in humans. Here, we investigate whether variations in estradiol levels across the follicular phase of the menstrual cycle modulate the effect of THC on inhibitory control in healthy women. Healthy female occasional cannabis users (N = 60) received THC (7.5 mg and 15 mg, oral) and placebo during either the early follicular phase, when estradiol levels are low, or the late follicular phase, when estradiol levels are higher. They completed a Go/No Go (GNG) task at the time of peak drug effect. We hypothesized that the effects of THC on GNG performance would be greater when estradiol levels were elevated. As expected, THC impaired GNG task performance: it increased response time and errors of commission/false alarms and decreased accuracy, relative to placebo. However, these impairments were not related to estradiol levels. These results suggest that THC-induced impairments in inhibitory control are not affected by cycle-related fluctuations in estradiol levels.