Mice implanted with morphine pellets demonstrated a 30-fold increase in tolerance to subcutaneously administered morphine but showed no cross-tolerance to subcutaneously administered heroin. When given morphine intracerebroventricularly, the mice showed no tolerance to morphine or cross-tolerance to heroin. These observations depended on the presence of the morphine pellet. If the pellets were removed prior to determinations of potency, the expected responses--tolerance to morphine and cross-tolerance to heroin--were obtained. The blood-brain barrier may be a prime site for the expression of morphine tolerance in mice.
The etfects of Δ9‐tetrahydrocannabinol (Δ9‐THC) administered orally at 2 dose levels were studied in a group of 7 healthy young adult males. Each subiect was studied for 7 nights (2 drug, 5 placebo). Vital signs, subiective feelings, deep tendon reflexes, electrocardiogram, electroencephalogram, visual evoked responses, postural responses, time estimation and reaction time and sleep patterns were studied. At the doses studied, Δ9‐THC increased pulse rate, altered subjective feelings, and caused hyperreflexia and upset postural responses in the absence of visual cues. Some subjects also exhibited lowered oral temperature, changes in averaged visual evoked response, and alteration of sleep patterns.
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