Neurodegenerative disorders such as dementia, multiple sclerosis (MS), and Alzheimer’s disease (AD) share neuroinflammatory characterization.
CB2 receptor agonists have shown neuromodulatory and immunomodulatory effects in the immune system.
β-Caryophyllene (BCP) is a CB2 agonist found in natural products such as cannabis, black pepper, Thai basil, and cloves. It has displayed anti-inflammatory and antioxidant effects through activation of the CB2 receptors.
Askari and Shafiee-Nick 2019 investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cell inflammation and M1/M2 imbalance and the involvement of related signaling pathways. 
They found that” the M2 healing phenotype of microglia provides the protective effects of BCP on LPS-induced microglia imbalance, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers”.
It is important to note that middle to higher BCP concentrations reduced the protective activity of BCP and resulted in the activation of the PPAR-γ pathway by SMase induction. It has also been found that SMase inhibitors imipramine (IMP) and fluoxetine (FLX) synergistically increase the protective effects of BCP.
Lindsey et al. 2019, showed that IL-23 levels are most strongly associated with aging in mice. They assessed changes in circulating cytokines in young and aged mice and BCP’s effects on memory function and cytokine load.
They found that BCP improved working memory and decreased IL-23 levels in aged mice. BCP appears to reverse age-associated impairments in memory in this animal study.
Further research is needed to determine whether CB2 agonists can play a role as novel anti- neurodegenerative disorders medications.
