Table 3. Combined estrogen/progesterone modulation of Δ9-THC-induced effects.
| Subjects | Treatment | Outcomes | Ref |
| 28 adult female humans | 1-gram standardized marijuana joint (1.83% Δ9-THC) or placebo joint during the follicular, luteal, and ovulatory phases | Menstrual cycle phase had no effect on marijuana-induced changes to pulse rate or subjective ratings of intoxication and confusion. | [38] |
| 30 adult female human with moderate-to-heavy marijuana use | No treatment; participants completed marijuana use diaries and the Moos Menstrual Distress Questionnaire (MDQ) daily for 3 consecutive menstrual cycles | No covariance of marijuana use and menstrual cycle phase. | [39] |
| Adult intact and ovariectomized female and intact male Lister Hooded and Long Evans rats | Ovarian hormone depletion (ovariectomy at 9-10 weeks of age and male rats) or presence (intact female rats); WIN self-administration acquisition, maintenance, and extinction | Intact females of both strains acquired WIN SA faster, administered more drug per session, and resisted extinction of WIN SA more robustly than did males and ovariectomized females. | [40] |
| Adult intact and ovariectomized female and intact male Lister Hooded rats | WIN self-administration acquisition and extinction; drug- and cue-induced reinstatement by priming with WIN (0.15 or 0.03 mg/kg, IP) with and without visual and/or auditory cues | Intact female rats reinstated WIN SA more robustly than did intact male or ovariectomized female rats across all drug- and cue-priming conditions. | [41] |
| Adult intact male and female Sprague-Dawley rats | Intracerebroventricular (ICV) administration of Δ9-THC (100 μg) five minutes before testing session | Females had shorter latencies to withdraw in nociceptive tests than males; females in estrus had shorter latency to withdraw than those in proestrus-estrus; Females in proestrus-estrus showed greater Δ9-THC-antinocieption than females in other phases and males. | [44] |
| Four-month old intact male and female Sprague-Dawley rats | Quantification of Δ9-THC and 11-OH- Δ9-THC in brain and serum 15, 30, 60, 120, and 240 minutes after Δ9-THC (10 mg/kg, IP); SKF525A (cytochrome P450 inhibitor, 25 mg/kg, IP) thirty minutes before Δ9-THC (10 mg/kg, IP) fifteen minutes before testing session; using HPLC | Females exhibited greater brain concentrations of 11-OH- Δ9-THC than males at 120 minutes post-injection; SKF525A decreased Δ9-THC-induced antinociception in females, but not males. | [45] |
| Adult gonadectomized or sham-gonadectomized female and male Sprague-Dawley rats | E2 (females) or testosterone (males) replacement or blank capsule controls (SC implants) immediately after gonadectomy; P (500 μg, SC, females only) or vehicle every 3 days, beginning 4 days after gonadectomy; 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 (10.0 mg/kg, IP) or vehicle 4 hours after final Δ9-THC treatment, 5 minutes before dependence testing session. | Sham-gonadectomized females developed greater tolerance to Δ9-THC-induced hypothermia than sham males; E2 and P increased rimonabant-induced chewing in chronic Δ9-THC-treated female rats. | [46] |
| Adult intact male and female Sprague-Dawley rats | ED80 dose of Δ9-THC (IP) or vehicle twice daily for 9 days; cumulative dosing of Δ9-THC (IP) on pre-chronic (1.8-32.0 mg/kg) and post-chronic (18.0-180.0 mg/kg) test days | Females developed greater tolerance to Δ9-THC-induced antinociception than males. | [47] |
| Adult gonadectomized or sham-gonadectomized female and male Sprague-Dawley rats | E2 (females) or testosterone (males) replacement or blank capsule controls (SC implants) immediately after gonadectomy; daily P (500 μg, SC, females only) or vehicle, beginning 4 days after gonadectomy; ED80 dose of Δ9-THC (IP) or vehicle twice daily for 9 days; cumulative dosing of Δ9-THC (IP) on pre-chronic (1.8-32.0 mg/kg) and post-chronic (18.0-180.0 mg/kg) test days | Females developed greater tolerance to Δ9-THC-induced antinociception than males in a non-ovarian-hormone- dependent manner. | [48] |
Note: Abbreviations: Δ9-THC, delta-9-tetrahydrocannabinol; E2, estradiol; HPLC, high performance liquid chromatography; ICV, intracerebroventricular (injection); IP, intraperitoneal (injection); μg, micrograms; MDQ, Moos Menstrual Distress Questionnaire; mg/kg, milligrams per kilogram; P, progesterone; SC, subcutaneous (injection).