In this latter study, Steffens and colleagues showed that oral administration of low doses of Δ9-tetrahydrocannabinol (THC, 1 mg/kg per day) significantly reduced plaque progression in apolipoprotein E (ApoE) knockout mice.
When indicated, the anti-estrogen ICI (1 μM) and the ER β inhibitor THC (1 μM) were added 30 min before E2 administration.
These data were further confimed by stimulating cells, in the absence and presence of E2 (10 nM), with the ER β antagonist (R,R -5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC, 1 μM), which did not inteR,R -5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediolCF-7 cells.
Multiple comparisons showed that the value of a was significantly increased by THC 1 and 3 mg kg−1 compared to the vehicle-alone treatment, reflecting the somewhat shallower slopes of the descending limbs of the response rate functions obtained with these doses (Fig. 3).
When indicated, the PAT inhibitor 2-Br (10 μM), the anti-estrogen ICI (1 μM), the ER β inhibitor THC (1 μM), the AKT inhibitor (1 μM), the p38 inhibitor SB (5 μM), the ERK1/2 inhibitor PD (1 μM), and the transcription inhibitor Act (1 μg/ml) were added 30 min before E2-MCF-7 cell proliferation was assessed by the XTT assay (Roche) according to the manufacturer's instructions.
Open image in new window Scheme. 1 Synthesis of pyrazole derivatives of THC (1 18).
Direct condensation of THC with various substituted hydrazines leads to new pyrazole derivatives of THC (1 18).
Abbreviations: THC Δ9-tetrahydrocannabinol, THC-COOH carboxy-Δ9-tetrahydrocannabinol.
THC (400 mg/kg) produced no antinociception.
A low dose of THC (50 mg/kg, i.p).
Immunoassays designed for THC metabolites (e.g., 11-nor-Δ9 THC-9-carboxylic acid, "9-carboxy-THC") generally do not cross-react with the synthetic cannabinoids that do not share the classic cannabinoid backbone found in THC [15].
