Comparative Toxicities of Tetrahydropyridobenzopyrans

Various forms of marihuana preparations have been used and abused for nearly 5,000 years (Rossi, 1970). However, precise systematic delineation of toxicologic and pharmacologic effects has only been possible since the recent isolation and identification of delta-9-tetrahydrocannabinol (delta-9-THC) as the major active component (Gaoni and Mechoulam, 1964), and delta-8-THC as a minor active constituent in cannabis (Hively, Mosher and Hoffman, 1966). The signs of acute toxicity produced by these cannabinoids in rats, dogs, and monkeys included severe hypothermia, bradypnea, rapid weight loss, ataxia, muscle tremors, prostration, and hyperreactivity to stimuli (Thompson, Rosenkrantz, Schaeppi and Braude, 1973). In addition, dogs and monkeys exhibited salivation, emesis, and drowsiness. Rats treated chronically with cannabinoids developed tolerance to most signs of depression and, ultimately, exhibited increased activity and convulsions (Thompson, Mason, Rosenkrantz and Braude, 1974). These cannabinoids, therefore, produced similar signs of toxicity in various species, but some species differences were apparent.