Simple SummaryWe believe it is essential to understand the effects of continuous cannabinoid administration on the requirements of inhalation anesthetics for patients administered general anesthesia and those administered morphine and dexmedetomidine. To understand the interaction of isoflurane with morphine and dexmedetomidine in rats treated repeatedly with the synthetic cannabinoid WIN 55,212-2, we determined the minimum alveolar concentration of isoflurane in 32 rats. We found that, in rats constantly medicated with the cannabinoid, the sparing effect of morphine on isoflurane decreased and the sparing effect of dexmedetomidine on isoflurane increased.AbstractThe impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. Methods: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC(ISO)) and those treated with a cannabinoid (MAC(ISO + CANN)). The effects of morphine (MAC(ISO + MOR)) and dexmedetomidine (MAC(ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC(ISO + CANN + MOR)) and (MAC(ISO + CANN + DEX) were also studied. Results: MAC(ISO)was 1.32 ± 0.06, and MAC(ISO + CANN)was 1.69 ± 0.09. MAC(ISO + MOR)was 0.97 ± 0.02 (26% less than MAC(ISO)). MAC(ISO + CANN + MOR)was 1.55 ± 0.08 (8% less than MAC(ISO + CANN)), MAC(ISO + DEX)was 0.68 ± 0.10 (48% less than MAC(ISO)), and MAC(ISO + CANN + DEX)was 0.67 ± 0.08 (60% less than MAC(ISO + CANN)). Conclusions: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.