Merck

The potential therapeutic effects of THC on Alzheimer's disease.

Journal of Alzheimer's disease : JAD (2014-07-16)
Chuanhai Cao, Yaqiong Li, Hui Liu, Ge Bai, Jonathan Mayl, Xiaoyang Lin, Kyle Sutherland, Neel Nabar, Jianfeng Cai
ABSTRACT

The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.

MATERIALS
Product Number
Brand
Product Description

Supelco
Melting point standard 235-237°C, analytical standard
Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Caffeine, SAJ special grade, ≥98.5%
Supelco
Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Supelco
Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Supelco
Caffeine, certified reference material, TraceCERT®
USP
Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Caffeine, BioXtra
Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Sigma-Aldrich
Caffeine, meets USP testing specifications, anhydrous
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
Sigma-Aldrich
Melatonin, powder, ≥98% (TLC)
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
USP
Caffeine, United States Pharmacopeia (USP) Reference Standard
USP
Melatonin, United States Pharmacopeia (USP) Reference Standard
Caffeine, European Pharmacopoeia (EP) Reference Standard