Figure 1.

Potential sites of action of the cannabinoid system for the treatment of AD. Activation of the CB₂ receptor reduces the formation of reactive oxygen species (ROS) and the release of interleukin-1β from microglia, thus exerting an anti-inflammatory effect. In neurones, activation of the CB₁ receptor reduces intracellular Ca²⁺ concentration ([Ca²⁺]_i), protects against oxidative stress and reduces inflammatory signalling by inhibition of nuclear factor κB. CB₁ activation also inhibits glutamate release to reduce excitotoxicity, and enhances neurotrophin expression and neurogenesis. CBD is neuroprotective and anti-inflammatory in a CB receptor-independent manner, and also reduces tau phosphorylation. Δ⁹-THC inhibits AChE, resulting in enhanced cholinergic transmission and reduced amyloidogenesis. AD, Alzheimer' disease; AChE, acetylcholinesterase; CB, cannabinoid; CBD, cannabinoid; Δ⁹-THC, Δ⁹-tetrahydrocannabinol.