Effect ofcannabis andcertain ofitsconstituents on pentobarbitone sleeping timeandphenazone metabolism

Summary 1.Cannabis extract prolonged sleeping timeinmiceinathermally neutral environment (30-32' C)inwhichhypothermia doesnotoccur. Theprolongation wasdoserelated, just detectable at50mg/kg, and4-fold at500mg/kg. 2.Underthese conditions, ether sleeping timewasnotprolonged. 3.Cannabis extract inhibited theaerobic metabolism ofphenazone bya microsome-rich 9,000 g supernatant ofmouseliver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH)generation. 4. A'-Tetrahydrocannabinol (A'-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, butitsaction waslimited, andcouldnot account fortheeffect oftheextract. Thecarotenes andwater-soluble fractions oftheextract wereinactive onpentobarbitone sleep. 5.Cannabidiol wasstrongly active bybothtests; invivo39-8tLM/kg (12-5 mg/kg) prolonged sleep by190%,andinvitro 12.7FMinhibited phenazone metabolism 20%.These actions weredoserelated, andcould account forthe effect oftheextract. 6.Theprolongation ofpentobarbitone sleep bycannabis extract inadoseof 200mg/kg, intraperitoneally, wasmaximal whengiven 30minbefore thepentobarbitone, still present at3h,butundetectable at24hours. Nophase ofenhanced metabolism at24or48hafter single cannabis injection wasdetected. 7.Itisconcluded that cannabis extract inhibits microsomal activity ofmouse liver, chiefly byvirtue ofitscannabidiol content. Itisprobable that cannabis consumption bymancould lead toaltered disposal ofmanyother drugs, used inmedicine orotherwise.