Cannabis sativa L. It is an annual herb in the mulberry family, also known as hemp, hemp, hemp, yam, jute. It has important agricultural and medicinal value, and is widely cultivated all over the world. As an ancient cultivated plant, marijuana has long been recorded. As early as 4000 years ago, marijuana was described in the Yellow Emperor's Canon of medicine. In the 2nd century AD, Hua Tuo, a famous Chinese doctor, used marijuana as an anesthetic for clinical treatment; "Compendium of Materia Medica" also has records of marijuana used as medicine; Its mature fruit, hemp seed, was also published in the 2005 edition of Chinese Pharmacopoeia. Because of its functions of moistening dryness, smoothing intestines, unblocking gonorrhea, and activating blood circulation, traditional Chinese medicine is used to treat intestinal dryness, constipation, thirst quenching, heat drenching, wind obstruction, dysentery, irregular menstruation, scabies, ringworm and other diseases.
In China, free cultivation and cultivation of marijuana are strictly prohibited. However, due to its special economic value and easy cultivation, the cultivation area of marijuana has been increasing throughout the world. . In addition, it also has a certain effect on glaucoma, asthma and cardiovascular disease. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the main chemical components in cannabis. Among them, thc is considered to be the most important active substance in cannabis, which has neural activity and can be used to treat vomiting caused by cancer. . With the in-depth study of cannabis, CBD has been found to hinder the effects of THC on the human nervous system, and has pharmacological activities such as anti spasm, anti rheumatoid arthritis, anti anxiety, etc.
At present,CannabidiolCBD has become a new hotspot in cannabis research. This paper reviews the research status of CBD, a non addictive component in cannabis.
Chemical structure of cannabidiol (CBD)
CBD was first isolated from Mexican marijuana and Indian marijuana by Adams and Todd in 1940. However, due to the limitation of experimental conditions at that time, errors occurred in the determination of CBD structure. Until 1963, mechoulam and shvo determined its exact chemical structure, which is the current general CBD structure. Since then, santavy gave the three-dimensional structure of CBD and published its relevant data in 1964; Jones determined the crystal structure of CBD in 1977 and reported two independent stereostructures of CBD (Fig. 1).
Biosynthetic pathway of cannabidiol: the C10 terpene part of CBD chemical structure is mainly synthesized through the deoxyxylulose phosphate pathway, and the phenol part is from the polyacetide type reaction sequence. It is believed that geranyl diphosphate (GPP) and polyacetic acid (OA) are special intermediates in the synthetic pathway of cannabidiol chemical components. . First, isopentene diphosphate (IPP) reacts with dimethyl allyl diphosphate (DM APP), and the generated GPP reacts with OA to generate CBG. CBG generates CBD, THC and their carboxylic acid compounds under the action of CBD synthase.
Chemical synthesis route of cannabidiol: the chemical synthesis route of cannabidiol has been reported in many literatures, and the most classical synthesis method is shown in (Figure 2)
ρ -mentha-2, 8-dien-1-ol reacted with Oliveto L under the catalysis of BF3 to obtain three products, of which the yield of (-) -cbd was 41%. Because the raw materials are relatively easy to obtain, the reaction is simple, and the yield of (-) -cbd is also high, it has been used as a common method to synthesize (-) -cbd for a long time.
Pharmacological study of cannabidiol (CBD)
It was only in the early 1970s that CBD had no cannabinoid bioactivity. However, in the following years, studies on the pharmacology of CBD, especially the anticonvulsant effect of CBD, have been reported successively. Since then, CBD has been reported to have anti emetic effect and can be used as an antioxidant and anti rheumatic arthritis drug in biological systems. ; Moreover, CBD exerts analgesic and anti-inflammatory effects through dual inhibition of cyclooxygenase and lipoxygenase, which is stronger than aspirin. After oral administration, CBD mainly displays the inhibitory effect on lipoxygenase; CBD, like THC, can stimulate the release of prostaglandins from synovial fluid cells. In recent years, people have modified the structure of CBD and synthesized a series of CBD analogues, which also have different pharmacological activities.
CBD has been reported to produce the regulatory product of TNF by human peripheral blood mononuclear cells. Due to the potential anti-inflammatory, low toxicity and non neurotoxicity of CBD, it has been used as a therapeutic agent for collagen induced arthritis, and also has a certain curative effect for the treatment of rheumatoid arthritis. In vitro experiments showed that CBD could significantly reduce TNF and no produced by peritoneal macrophages. Fride et al. Found that (+) - 7-oh-cannabidiol-dmh had central activity in central and peripheral anti-inflammatory and anti peripheral pain in mouse intestine through (+) - CBD and its analogues, and (+) - cannabidiol DMH could inhibit peripheral pain in mouse ear and inflammatory symptoms induced by arachidonic acid. Other pharmacological effects: CBD also has antioxidant effect, can resist glutamate neurotoxin (stronger than ascorbate or vitamin E), and is a potential antioxidant. In addition, CBD also has anti diazepam effect and anti gram positive bacteria effect; It is effective in controlling dystonia movement disease and myasthenia gravis. The CBD analog △ 6-cbd has thc like activity.
Cannabidiol, the first cannabis drug approved by FDA
FDA also approved cannabidiol from GW（Cannabidiol）, for Lennox Gastaut syndrome and Dravet syndrome treatment. Cannabidiol is a monomer extracted and isolated from cannabis, and it is the first cannabis drug approved by FDA.
A multicenter clinical trial (nct02224560) involving 225 patients with Lennox Gastaut syndrome showed that the frequency of seizures in the cannabidiol treatment group was significantly lower than that in the placebo group, with a decrease of 17.2% in the placebo group, 37.2% in the 10mg/kg treatment group, and 41.9% in the 20mg/ kg treatment group. .
expectation
Cannabis, as an important cash crop in the world, is banned in various countries because its leaves contain neuroactive THC, which can be used as a drug, which limits the development of cannabis to a certain extent. .
In many regions of China, especially in Shandong, Anhui, Gansu, Yunnan and other traditional marijuana producing areas, thousands of acres of fiber-based industrial marijuana are planted. However, after extracting marijuana fiber, the remaining material is often discarded, which not only pollutes the environment but also wastes resources. The research on the chemical composition of marijuana, especially the research on CBD, has played a positive role in making more rational use of marijuana resources and turning waste into treasure in the future.
CBD, a non addictive component in marijuana, shows a variety of pharmacological activities, but the mechanism of action of CBD is not yet clear, which requires further research. At present, people's research on the stereoorientation of CBD, antioxidation and CBD analogues is of great significance for better studying the structure-activity relationship of CBD analogues and elucidating their mechanism of action. At the same time, the research of CBD analogues undoubtedly provides a broader prospect for the development of new anti diarrhea, anti-inflammatory and analgesic drugs.