Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APPPS1 Mice.
Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimers disease (AD) have been sparse due to the concern about THCs psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-β (Aβ) production was examined in N2aAβPPswe cells. An in vivo study was conducted in aged APPPS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mgkg every other day for three months. The in vitro study showed that THC inhibited Aβ aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mgkg of THC for three months significantly improved the spatial learning performance of aged APPPS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aβ oligomers, phospho-tau and total tau, and increased the expression of Aβ monomers and phospho-GSK-3β (Ser9) in the THC-treated brain tissues. In conclusion, treatment with THC at 0.2 and 0.02 mgkg improved the spatial learning of aged APPPS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.