Table 4. Estrogen modulation of Δ⁹-THC-induced effects.

Subjects	Treatment	Outcomes	References
Ovariectomized female Long-Evans rats	The dose-effect of Δ9-THC (0.56-3.2 mg/kg, IP) on repeated acquisition and performance of a 4-response sequence memory and learning operant task in the presence of either E2 replacement or cholesterol control via SC implanted capsule	E2 alone improved response accuracy. E2 attenuated the Δ9-THC-induced reduction in response accuracy during acquisition and performance and reduction in response rate during acquisition.	[42]
Intact or ovariectomized female Sprague-Dawley rats	E2 replacement or blank capsule controls (SC implants) immediately after ovariectomy; determination of estrous cycle phase of intact females by daily vaginal lavage; acute Δ9-THC (5 or 10 mg/kg, IP) 15 minutes before testing session	E2 enhanced Δ9-THC-induced antinociception; Δ9-THC-induced antinociception was greatest during the estrus phase in intact cycling females; E2 had no effect on Δ9-THC-induced locomotor supression or catalepsy; Testosterone attenuated Δ9-THC-induced locomotor suppression.	[43]
Adult ovariectomized or sham- ovariectomized female Sprague-Dawley rats	E2 replacement or blank capsule controls (SC implants) immediately after ovariectomy; P (500 μg, SC) or vehicle every 3 days, beginning 4 days after ovariectomy ; Δ9-THC (30 mg/kg, IP) or vehicle twice daily for 6.5 days, with the final dose administered 30 minutes before tolerance testing session. Rimonabant (10 mg/kg, IP) or vehicle were administered 4 hours later, 5 minutes before dependence testing session	E2 increased locomotor activity in Rimonabant-treated ovariectomized female rats.	[46]

Note: Abbreviations: Δ⁹-THC, delta-9-tetrahydrocannabinol; E2, estradiol; IP, intraperitoneal (injection); μg, micrograms; mg/kg, milligrams per kilogram; P, progesterone; SC, subcutaneous (injection).