Mifepristone or inhibition of 11beta-hydroxylase activity potentiates the sedating effects of the cannabinoid receptor-1 agonist Delta(9)-tetrahydrocannabinol in mice.
The cannabinoid system is a regulator of neurotransmission and is linked with hormonal control. We have found in experimental mouse studies that the progesterone receptor inhibitor mifepristone (RU38486, 80 mg/kg i.p.) or the 11beta-hydroxylase inhibitor metyrapone (100 mg/kg i.p.) when administered in combination with cannabinoids potentiates the transient-sedating cannabinoid receptor-1 effects of a high-dose Delta(9)-tetrahydrocannabinol (25 mg/kg i.p.), causing severe prolonged sedation associated with hypomotility, catalepsy and hypothermia. This observation has implications for human subjects taking these drugs and related compounds particularly because of the ubiquitous use of cannabis and the high potential for mifepristone and related compounds to become available on the 'black-market' as abortifacients.
Pryce
Gareth
G
Department of Neuroinflammation, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, WC1N 3BG, London, UK.
Giovannoni
Gavin
G
Baker
David
D
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D016292:Procedural Sedation; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D015735:Mifepristone; D013759:Dronabinol; D008797:Metyrapone