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Pryor GT, Husain S, Mitoma C, Braude MC. 
“Acute and Subacute Interactions Between delta-9-Tetrahydrocannabinol and Other Drugs in the Rat”. 
Ann.N.Y.Acad.Sci.. 1976;281:171 -89.
Interactions between delta-9-tetrahydrocannabinol (delta-9-THC) and other drugs in the rat were studied. Methods 5 Tests were made in 55-60 day old male rats (conditioned pole-climb avoidance (CAR), photocell activity, heart rate (HR) body temperature and rotarod performance) to study interaction between various doses of p.o. delta-9-THC in sesame oil or aqueous vehicle and various doses of other i.p. drugs: d-amphetamine, methamphetamine, cocaine, caffeine, nicotine, chlordiazepoxide methaqualone, phenobarbital, ethanol, phencyclidine, LSD-25, lithium chloride, desmethylimipramine, diphenylhydantoin, tolbutamide, acetylsalicylic acid. Drugs were given subacutely for 6 days and acutely 2 hr and 30 min before testing on day 7. Results Acute administration of delta-9-THC caused dose-related decrease in all 5 tests; most variability in results was seen in all except HR and photocell activity tests. Subacute 10 mg/kg delta-9THC created tolerance in all tests, complete to CAR impairment and partial to bradycardia and hypothermia. Plasma levels of total radioactivity after 40 microCi/kg 34C-delta-9-THC were maximal at 2-4 hr; highest levels were found in liver and lowest in plasma and brain. Unchanged q-THC accounted for 12-14 0n plasma. Control levels were reached by 8 hr. A substantial tissue pool accumulated after repeated administration. With interaction studies, depressant properties of delta-9-THC tended to predominate regardless of the pharmacological properties of the interacting drug. Stimulants (d-amphetamine and cocaine) failed to antagonise the depressant effects; nicotine and chlordiazepoxide potentiated them although inactive on their own and the other 6 drugs, showing varying degrees of depression alone, potentiated delta-9-THC effects further. Observed interactions were often complex and depended on respective doses and the animal's previous exposure to either or both drugs and the test used. Tolerance to delta-9-THC in subacute studies tended to extend to interactions causing an attenuation of their acute combinations. Changes in interactions following subacute administration with the other drugs were less general.
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