Cannabinoids: neurochemical aspects after oral chronic administration to rats

Male and female Fischer rats were treated orally with Δ⁹-THC doses between 50 and 500 mg/kg or with crude marihuana extract between 50 and 1500 mg/kg, for 28 or 91 consecutive days. At necropsy, brains were weighed and kept frozen until 10% homogenates in 0.32 m sucrose could be made and analyzed. Homogenate samples were assayed for total protein, RNA, lipids, and acetylcholinesterase, succinic dehydrogenase and monoamine oxidase activities. Significant decreases were obtained for protein, RNA and acetylcholinesterase activity at 28 days and monoamine oxidase at 91 days. No changes in total lipids, glycolipids or cholesterol concentrations were observed. The neurochemical alterations coincided with behavioral symptoms of hyperactivity and convulsive activity. Both neurotoxicity and neurochemical changes were partially reversed after the longer interval of treatment.