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Research Survey of Cannabidiol, a Non-addictive Component in Cannabis

Cannabis sativa-L. It is an annual herbaceous plant of the Hemp family, also known as mountain silk seedling, and jute. 

It has important agricultural and medicinal value and is widely cultivated all over the world. As an ancient cultivated plant, hemp has been recorded for a long time. As early as 4000 years ago, there was a description of hemp in the “Huang Di Nei Jing”. 

In the 2nd century AD, my country’s famous doctor Hua Tuo used cannabis as an anesthetic for clinical treatment; “Compendium of Materia Medica” also has a record of cannabis used as medicine; its mature fruit hemp seed is also included in the  Pharmacopoeia 2005 edition. Because it has the effects of Moisturizing, smoothing the intestines, clearing leaching, and promoting blood circulation, traditional medicine treats diseases such as dry intestines, constipation, diarrhea, heat leaching, wind arthralgia, dysentery, irregular menstruation, scabies, ringworm, etc.

The free cultivation and cultivation of cannabis is strictly prohibited in our country. However, due to its special economic value and easy cultivation, the area of ​​cannabis planted in the world has always been increasing. The main active ingredient in cannabis is cannabinoids. There are currently 70 known natural cannabinoids, which are mainly used for multiple sclerosis, motor neuropathy, chronic intractable pain and certain neurological diseases. Drug-induced vomiting. 

In addition, it has a certain effect on glaucoma, asthma and cardiovascular diseases. Tetrahydrocannabinol (THC) and cannabidiol (Cannabidiol, CBD) are the main chemical components contained in cannabis. Among them, THC is considered to be the most important active substance in marijuana. It has neurological activity and can be used to treat vomiting caused by cancer. 

But THC has hallucinogenic effects, which has become the only reason why cannabis is banned in many countries. With people’s in-depth research on marijuana, it is found that CBD can hinder the effect of THC on the human nervous system, and has anti-spasm, anti-rheumatoid arthritis, anti-anxiety and other pharmacological activities.

At present, cannabidiol (CBD) has become a new hot spot in cannabis research. This article reviews the research status of CBD, a non-addictive component of cannabis.

The chemical structure of cannabidiol (CBD)

CBD was first isolated from Mexico and Indian hemp by Adams and Todd in 1940, but due to the limitation of experimental conditions at that time, there was an error in determining the structure of CBD. It was not until 1963 that Mechoulam and Shvo determined its exact chemical structure, which is the current general CBD structure. After that, Santavy gave the three-dimensional structure of CBD in 1964 and published its related data; Jones determined the crystal structure of CBD in 1977 and reported two independent three-dimensional structures of CBD. 

Cannabidiol (CBD) biosynthesis and chemical synthesis

The biosynthetic pathway of cannabidiol: The C10 terpene part in the CBD chemical structure is mainly synthesized through the deoxyxylulose phosphate pathway, and the phenol part comes from the polyketide-type reaction sequence (polyketide-type reaction sequence), and it is considered that the geranyl Diphosphoric acid (GPP) and polyacetic acid olivetolic acid (OA) are special intermediates in the synthesis of cannabis chemical components. 

People have discovered CBD synthase that synthesizes CBD from cannabidiol (CBG). Firstly, isopentenyl diphosphate (IPP) and dimethyl propenyl diphosphate (DMAPP) react, and the generated GPP reacts with OA to generate CBG. CBG generates CBD, THC and its carboxylic acid compounds under the action of CBD synthase.

The chemical synthesis pathway of cannabidiol: There are many reports on the chemical synthesis pathway of cannabidiol, the most classic synthesis method. 

ρ-mentha-2,8-dien-1-ol reacts with olivetol under the catalysis of BF3 to obtain 3 kinds of products, among which the yield of (-)-CBD is 41%. Since 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 for the synthesis of (-)-CBD for a long period of time.

Pharmacological research of cannabidiol (CBD) 

It was only in the early 1970s that CBD had no biological activity of cannabinoids. But in the following years, there have been reports on the pharmacological aspects of CBD, especially the anticonvulsant effect of CBD. Since then, it has been reported that CBD has an anti-emetic effect and can be used as an antioxidant and anti-rheumatoid arthritis drug in biological systems. 

Relevant pharmacological studies have shown that CBD has a regulatory effect on the level of THC in the brain; and CBD exerts analgesic and anti-inflammatory effects through dual inhibition of cyclooxygenase and lipoxygenase, and is stronger than aspirin, the main manifestation after oral administration In order to inhibit lipoxygenase; CBD, like THC, can stimulate the release of prostaglandins from synovial cells. 

In recent years, people have modified the structure of CBD and synthesized a series of CBD analogs, which also have different pharmacological activities.

It has been reported that CBD produces TNF regulatory products through human peripheral blood monocytes. Due to the potential anti-inflammatory, low toxicity and non-neurotoxicity of CBD, some people use it as a therapeutic agent for collagen arthritis, and it also has a certain effect on the treatment of rheumatoid arthritis.

In vitro experiments show that CBD can significantly reduce TNF and NO produced by peritoneal macrophages through (+)-CBD and its analogues on the central and peripheral anti-inflammatory and anti-peripheral pain in the mouse intestines found that (+)-7-OH-cannabidiol-DMH has central activity, (+)- cannabidionl-DMH can inhibit mouse ear peripheral pain and arachidonic acid-induced inflammatory symptoms. 

Other pharmacological effects: CBD also has an antioxidant effect, can resist glutamate neurotoxin (stronger than ascorbate or vitamin E), and is a potential antioxidant. In addition, CBD also has anti-stabilizing effects and anti-Gram-positive bacteria effects; it is effective in controlling dystonic movement diseases and dystonia. The CBD analog △6-CBD has THC-like activity.

Outlook

Cannabis is an important international economic crop. Because its leaves contain neuroactive THC that can be used as a drug, it is included in the ban in various countries, which limits the development of cannabis to a certain extent. 

In order to take advantage of the disadvantages, internationally, through variety improvement, industrial hemp was cultivated, and the content of THC was reduced to less than 0.3% for medicinal use.

In many areas of our country, especially traditional hemp producing areas such as Shandong, Anhui, Gansu, and Yunnan, there are thousands of acres of fiber-use industrial hemp planted. 

However, after hemp fiber is extracted from it, the remaining materials are often discarded It not only pollutes the environment but also wastes resources. The research on the chemical composition of hemp, especially the CBD, will play a positive role in the more rational use of hemp 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, and further research is needed. At present, people’s research on the stereospecificity of CBD, the research on anti-oxidation, and the research on CBD analogs are of great significance for better studying the structure-activity relationship of CBD analogs and elucidating the 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. 

 Addictive or not? 

Recent studies have shown that the cannabinoid CBD (cannabidiol) has a good pain relief effect. 

American Marijuana’s CBD consumer survey this time is to study the possibility of CBD replacing opioids from the perspective of consumers.

What kind of pain can consumers relieve with CBD?

Among the thousands of consumers interviewed by American Marijuana, 60% of CBD consumers use CBD to relieve “chronic pain”, 34% use CBD to relieve “migraine”, 28% use CBD to treat “joint pain”, and 3% use CBD To relieve the “pain in cancer treatment.”

How effective is CBD in relieving pain?

53% of the interviewees said that they use CBD as the only medicine for pain relief; 32% of people use CBD for pain relief for a long time without any tolerance; 44% said that they have never had side effects.

Can CBD reduce opioid use?

Among the interviewees, 259 people used opioids for pain relief for a long time. After using CBD, 40.15% of them stopped using opioids at all, and 57.14% reduced their opioid doses.

Can CBD relieve the symptoms of opioid withdrawal?

Among the respondents who used opioids, 73% said that their opioid withdrawal symptoms were alleviated after using CBD; only 3% of them did not get any relief after using CBD.

On May 21, 2019, researchers from the Icahn School of Medicine at Mount Sinai published a study in the American Journal of Psychiatry. The data of this study shows that oral cannabidiol CBD can reduce drug cravings and anxiety of opioid addicts and help addicts to quit opioids.

Can CBD effectively replace opioids?

Among the respondents who used opioids, 84.45% gave an affirmative answer, and only 15.55% thought no.

Compared with opioids, what are the advantages of CBD for pain relief?

Respondents said that the advantages of CBD to relieve pain are “not addictive (35%)” and “fewer side effects (36%)”.

Tory R. Spindle , Ph.D. from the Johns Hopkins University School of Medicine, said, “The results of this investigation are consistent with the conclusions of other recent studies. CBD can effectively relieve pain.”

But Tory also pointed out, “Further controlled studies are needed to understand the analgesic effect of CBD. Because if there is no controlled study, some people may have analgesic effect due to the placebo effect. They heard from friends that CBD can relieve pain, so In the heart.”

Dr. Prakash Nagarkatti , Vice President of the University of South Carolina , said, “Our laboratory has been studying cannabinoids for more than 20 years. According to our research, CBD is very effective against autoimmune and inflammatory diseases. Inflammation can cause pain, and CBD can inhibit pain. It comes from its anti-inflammatory properties.”

Rhet Smith , a professor at the University of Arkansas, Little Rock, said, “This information is very important. The opioid crisis is becoming more and more widespread. It is good to know other alternative pain relief drugs. With these findings, we can make more Good treatment option.”

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