“Background
Alzheimer’s disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential.”
“Cannabinoids, whether plant derived, synthetic or endocannabinoids, interact with two well characterized cannabinoid receptors, CB1 and CB2 . In addition, some cannabinoids may interact with other receptors, such as the TRPV1 receptor or the orphan receptor GPR55. The CB1 receptor is widely distributed, with a particularly high expression in brain, which contrasts with the limited expression of the CB2 receptor, which is characteristic of immune organs and cells. In fact, while CB1 receptors are expressed by all types of cells in the brain (neurons and glial cells), CB2 are mainly localized in microglial cells, the resident immune cell of the brain.”
“We and others have proposed cannabinoids as preventive treatment for AD, based on their neuroprotective and anti-inflammatory effects. Indeed, cannabinoids are able to decrease the release of cytokines and nitric oxide in cultured microglial cells induced by lipopolysacharide and Aβ addition. In several in vitro studies cannabidiol (CBD), the major non-psychotropic constituent of cannabis, has shown to be neuroprotective against β-amyloid (Aβ) addition to cultured cells.”
“Conclusions
In summary, cannabinoid agonists, in particular CB2 selective agonists, interfere with several interconnected events of importance in the pathophysiology of AD. These compounds by directly interacting with cannabinoid receptors, in particular CB2, decrease microglial activation thereby reducing inflammation and its consequences (eg cognitive deficits). At the same time they may indirectly have beneficial effects on microglial activation (eg decrease cytokine release) by lowering brain Aβ levels.”