Enhanced susceptibility of mice to combinations of delta 9-tetrahydrocannabinol and live or killed gram-negative bacteria.
Combinations of delta 9-tetrahydrocannabinol (delta 9-THC) and bacterial endotoxin were shown to be hyperadditively toxic for mice. A variety of purified lipopolysaccharide (LPS) preparations elicted enhanced mortality in combination with delta 9-THC. Escherichia coli O26:B6 LPS (Boivin preparation) at an essentially nonlethal dose of 2.5 mg/kg reduced the dose of delta 9-THC required to kill 50% of the treated mice from ca. 350 to 150 mg/kg. Inbred BALB, DBA, and C3H/HeCr mice, noninbred ICR mice, and hybrid CDF1 and BDF1 mice were hyperreactive to combinations of delta 9-THC and LPS. Moreover, a variety of heat-killed intestinal and gram-negative bacteria, live E. coli, and complexes of lipid A with a variety of proteins substituted for LPS in the synergistic toxicity of LPS and delta 9-THC. Extracts of marijuana also elicited hyperreactivity to LPS. The hyperadditive lethality of combinations of delta 9-THC and LPS was markedly less in mice rendered refractory to LPS or delta 9-THC by repeated administration of LPS or delta 9-THC, respectively.
D000818:Animals; D013759:Dronabinol / Q000633:toxicity*; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006358:Hot Temperature; D008050:Lipid A / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D011041:Poisoning / Q000401:mortality; D011135:Polysaccharides, Bacterial / Q000633:toxicity*; D011549:Pseudomonas
D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D013759:Dronabinol