Marijuana extracts possess the effects like the endocrine disrupting chemicals.
The progesterone 17alpha-hydroxylase activity, which is one of the steroidogenic enzymes in rat testis microsomes, was significantly inhibited by crude marijuana extracts from Delta(9)-tetrahydrocannabinolic acid (THCA)- and cannabidiolic acid (CBDA)-strains. Delta(9)-Tetrahydrocannabinol, cannabidiol and cannabinol also inhibited the enzymatic activity with relatively higher concentration (100-1000 microM). Testosterone 6beta- and 16alpha-hydroxylase activities together with androstenedione formation from testosterone in rat liver microsomes were also significantly inhibited by the crude marijuana extracts and the cannabinoids. Crude marijuana extracts (1 and 10 microg/ml) of THCA strain stimulated the proliferation of MCF-7 cells, although the purified cannabinoids (THC, CBD and CBN) did not show significant effects, such as the extract at the concentration of 0.01-1000 nM. These results indicate that there are some metabolic interactions between cannabinoid and steroid metabolism and that the constituents showing estrogen-like activity exist in marijuana.
Watanabe
Kazuhito
K
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. k-watanabe@hokuriku-u.ac.jp
Motoya
Erina
E
Matsuzawa
Naoki
N
Funahashi
Tatsuya
T
Kimura
Toshiyuki
T
Matsunaga
Tamihide
T
Arizono
Koji
K
Yamamoto
Ikuo
I
D000735:Androstenedione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002186:Cannabinoids / Q000633:toxicity; D002187:Cannabinol / Q000633:toxicity; D002188:Cannabis / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D065607:Cytochrome P-450 Enzyme Inhibitors; D013759:Dronabinol / Q000633:toxicity; D005260:Female; D006213:Hallucinogens / Q000737:chemistry / Q000633:toxicity*; D006727:Hormone Antagonists / Q000378:metabolism / Q000633:toxicity; D006915:Hydroxytestosterones / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D002186:Cannabinoids; D065607:Cytochrome P-450 Enzyme Inhibitors; D006213:Hallucinogens; D006727:Hormone Antagonists; D006915:Hydroxytestosterones; D010936:Plant Extracts; D013739:Testosterone; D000735:Androstenedione; D013759:Dronabinol; D002187:Cannabinol; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; C022445:progesterone 17-alpha-hydroxylase; C006884:cannabidiolic acid