Effects of chronic administration of delta 9-transtetrahydrocannabinol (delta9-THC) in guinea-pigs.

The guinea-pigs were divided into three groups: (1) absolute control, (2) solvent control (tween 4%), and (3) delta9-THC group (3 mg/kg). The selected dose of delta9-THC corresponds to the minim amount producing physiological effects in acute administration and was given for six months at the rate of five injections/week. The results showed that THC produced no changes on these parameters: serum glucose, urea nitrogen, total proteins, Mg, Ca, Na, and K. However, the fatty acids and alpha1 globulin were significantly decreased. There was a significant increase in gamma globulin. The body weight gain of delta9-THC treated animals was lower than of the two controls. Delta9-THC decreased the relative weight of liver and spleen; however, it did not significantly affect the relative weight of heart, adrenals, and kidneys. Similarly, the morphological examinations showed no alteration in these tissues, except in the liver tissue, where a perturbation of the autodigestion of glycogen was noted. These observations suggest that the toxic effect of the drug is caused by its accumulation in the liver, which provokes an inhibition of certain liver enzymatic systems.