Effect of cannabinoids on the turnover rate of acetylcholine in rat hippocampus, striatum and cortex.

The effects of delta9-tetrahydrocannabinol (delta9-THC), the major psychoactive compound of marijuana, and cannabidiol (CBD), a non-psychoactive component, on the acetylcholine (ACh) concentration and the turnover rate of ACh (TRACh) have been studied in various regions of the rat brain. Neither delta9-THC doses from 0.2 to 10 mg/kg nor CBD (10 OR 20 MG/KG) alter the ACh concentration in the brain areas examined 30 min, after the intravenous injection. However, delta9-THC (doses from 0.2 to 10 mg/kg) causes a marked dose-related decrease in the TRACh in hippocampus whereas CBD is without effect in this brain region even when 20 mg/kg is given. Furthermore, high doses of delta9-THC (5 mg/kg) and CBD (20 mg/kg) that produce a significant decrease in the TRACh of striatum fail to change the TRACh in parietal cortex. The low doses of delta9-THC required to reduce hippocampal TRACh suggest that an action on these cholinergic mechanisms may play a role in the psychotomimetic activity of delta9-THC.