Toxicity of Δ9‐tetrahydrocannabinol (THC) administered subcutaneously for 13 days to female rabbits

Abstract
Δ9‐Tetrahydrocannabinol (THC) was administered subcutaneously to female New Zealand white strain rabbits for 13 days. The animals were randomly divided into six groups of five animals each of which consisted of untreated controls, vehicle (undiluted propylene glycol)‐treated, and THC treatment at dose levels of 100, 30, 10, and 3 mg/kg/day. All animals survived for the duration of the study. The THC‐treated rabbits did not gain significant body weight, which seems to be due to a decreased food consumption. There were some variations in various hematologic values, but they all were within the normal range for our laboratory. Blood chemistry evaluations showed decreased serum levels of potassium, glucose, blood urea nitrogen, alkaline phosphatase, and albumin/globulin (A/G) ratio and an increase in cholesterol levels of all treated animals. A significant increase in bilirubin values was noted in the animals of the 3‐ and 10‐mg/kg groups. The injection site in the skin of the THC‐treated rabbits showed signs of local irritation (erythema and subcutaneous abscesses). There was a reduction in absolute and percent of body weight of the liver and absolute weight of the lungs of the treated animals. However, no histopathologic alterations were observed. It may be concluded that THC treatment subcutaneously for 13 days in rabbits up to a dose level of 100 mg/kg/day did not produce any significant toxicity, except anorexia and some local dermal irritation.