Comprehensive review of cannabis including cannabinoid brain function

Abstract

Cannabis sativa L. is cultivated for several thousand years. Cannabinoid research has been started from the 1940s and more than 100 species are structurally determined in recent years. The biosynthetic research of cannabinoids started using labelled compounds, followed by the isolation and cloning of their biosynthetic enzymes. Among them tetrahydrocannabinolic acid (THCA) synthase was found to be a flavoenzyme. This enzyme was overexpressed in a baculovirus system and crystallized. The exact structure was determined by X-ray crystallography resulting in determination of reaction mechanism. To efficiently promote THC metabolic studies anti-THCA monoclonal antibodies was prepared to isolate and structurally determine THC metabolites in vivo and define metabolic pathways. Two receptors CB1 and CB2 for cannabinoid were discovered and two endogenous ligands for them. Rapid progress is being made on the relationship between the endocannabinoid system and brain function. THC is currently marketed for nausea, vomiting, weight loss, and sleep apnea. CBD was approved for the treatment of intractable epilepsy. Therefore, dementia will be discussed in this review because dementia has recently become a major social issue worldwide. THC inhibits acetylcholinesterase and Aβ condensation in vitro. CBD showed antioxidant, anti-inflammatory and neuroprotective effects on mice treated with human Aβ protein. CBD and THC were used together, the therapeutic effect was much stronger than with CBD alone, and the effect showed an aspect of antagonistic response. Therefor, CBD is an excellent candidate for AD treatment as its mechanism of action and medicinal effects differ from those of other drugs, and it also acts as a prophylactic agent against AD without side effects such as dependence and/or hallucinogenic effects like THC. Clinical studies have been conducted with THC and/or CBD, or their products, and have shown anti-recognition effects, but of course side effects of THC have been observed and no conclusion has been reached as to whether THC or CBD is better for clinical use.