Views: 0 Author: Site Editor Publish Time: 2022-01-11 Origin: Site
In the early 1990s, Matsuda and Munro, among others, discovered two cannabis receptors, one consisting of 473 amino acids called the central type of cannabis receptor, named CB1. CB1 receptors are mainly located in the brain, spinal cord and peripheral nervous system including the lungs, heart, genitourinary, gastrointestinal tract and eyes.
Human CB1 is very similar to that of rats, but one less amino acid. The other, which consists of 360 amino acids, is called an external cannabis receptor and is named CB2. CB2 receptors are mainly distributed in the peripheral areas, such as the limbic area of the spleen, the surface of immune cells, and the tonsils.
The differences in the organizational distribution of CB1 and CB2 are not absolute, but the amount of expression is different. Highly expressed CB1 in brain tissues is shown to be microexpressed in peripheral tissues such as the adrenal glands, heart, lungs, prostate, uterus, ovaries, testicles, bone marrow, thymus, spleen, and tonsils.
Both CB1 and CB2 belong to the diphtheria toxin-sensitive inhibitory G protein receptors, which inhibit the activity of adenylate cyclase by inhibiting the protein (Gi), which reduces intracellular cAMP levels. Wiley and Fride, among others, speculated through pharmacological experiments that there was a new cannabinoid receptor, which Ester called the CB3 receptor, but did not have sufficient evidence to confirm the existence of this receptor.
A large number of pharmacological studies have shown that THC (tetrahydrocannabinol) regulates central and peripheral neurotransmission by acting on CB1 receptors, and produces a variety of biological activities by acting on CB2 receptors to regulate cytokines released from immune cells. However, there are no relevant reports on the mechanism of action of CBD, but there is no doubt that CBD without neural activity has pharmacological activity, and its pharmacological effect is not the same as THC.
Pharmacological studies of CBD were only available in the early 1970s. In the following years, studies on the pharmacology of CBD were reported successively, especially the anticonvulsant effect of CBD, and the anti-vomiting effect of CBD and its ability to act as an antioxidant and anti-rheumatoid arthritis drug in biological systems.
Related pharmacological studies have shown that CBD has a regulatory effect on THC levels in the brain; and CBD exerts analgesic and anti-inflammatory effects through the dual inhibition of cyclooxygenase and lipoxygenase, and is stronger than aspirin, which is mainly manifested as an inhibitory effect on lipoxygenase after oral administration; CBD, like THC, can stimulate the release of prostaglandins from synovial cells. In recent years, people have modified the structure of CBD to synthesize a series of CBD analogues, which also have different pharmacological activities.
The pathogenesis of inflammation is complex , inflammation is caused and maintained through various intercellular mediators. Among them, tumor necrosis factor (TNF) is also involved in the process of inflammation formation and plays a particularly important role. The antibacterial and antitumor activity of antioxidant media (ROIs) plays a key role in protecting the body. Nitric oxide (NO) is an endogenous regulator with a variety of biological functions, which also exhibits antibacterial and anti-tumor activity and affects all aspects of the inflamed lamination.
High levels of TNF, ROI, and NO in the body can cause inflammation, damage the body's cells and tissues, and cause sepsis. Therefore, the use of drugs acting on the immune system to suppress TNF, ROI, and NO is a major target in the treatment of inflammation.
CBD has been reported to produce regulatory products of TNF through human peripheral blood monocytes. Due to the potential anti-inflammatory, low toxicity and non-neurotoxicity of CBD, it has been used as a therapeutic agent for collagen arthritis and has a certain effect on the treatment of rheumatoid arthritis.
In vitro experiments have shown that CBD can significantly reduce TNF and NO produced by peritoneal macrophages. Fride et al. (+)-CBD and its analogues have found that (+)-7-OH-cannabidiol-DMH has central activity, and (+)-cannabidionl-DMH can inhibit peripheral pain in the ears of mice and symptoms of inflammation induced by arachidonic acid.
In a series of endpoint indicators, cannabidiol was consistently superior to placebo, with the most obvious differences being the PANSS positive scale, the severity clinical overall impression scale, and the clinical overall impression scale of improvement. Compared with placebo-treated patients, the proportion of patients responding to cannabidiol (panss overall score improvement greater than 20%) was higher, with a odds ratio of 2.65.
In terms of cognition, cannabidiol is superior to placebo, with significant differences observed in sub-domains that are particularly associated with improved outlook in patients with schizophrenia. For negative symptoms, the negative symptom assessment scale shows a trend in support of cannabidiol, and this trend has reached a significant difference in patients taking cannabidiol plus a major first-line antipsychotic. Most of the other endpoints in the study supported cannabidiol, and in most cases were close to statistical significance.
Musty's experiments with mice found that CBD can relieve stress and reduce ulcers due to stress. A team of researchers in Brazil found that CBD can stop anxiety produced by THC and even has an inhibitory effect on other central nervous system effects caused by THC. Of course, not all THC effects can be blocked by CBD.
The team also conducted a double-blind experiment with Diazepam and CBD, confirming that CBD is equally sedative in addition to taking a higher dose than Diazepam. Later, the team found that the dimethylheptyl analogue of CBD was better than the sedative effects of pacifera and CBD.
Brain tumors are not only difficult to treat, but also have a poor prognosis. Recently, scientists have shown that some components of cannabis combined with radiation therapy to treat brain cancer can basically completely inhibit the growth of tumors. Its main role compounds are tetrahydrocannabinol (THC) and cannabidiol (CBD).
Cannabis is the active chemical in cannabis, there are 85 known cannabis-like constituents in the cannabis plant, and the main active ingredient in cannabis is called tetrahydrocannabinol (THC). The results of this study are the first to demonstrate that the study mainly targeted brain tumors in mice, and when THC/CBD was used in combination with radiation therapy, tumor growth slowed down significantly.
Researcher Dr. Wai Liu said: "The results are very exciting. In the experiment, three methods were used for tumor treatment, marijuana alone, radiation alone, and radiation and cannabinoids at the same time. The results found that the combination of radiation and cannabinoids gave the most favorable results, and the tumor size was greatly reduced. Even in some cases, animal brain tumors can disappear completely. The research team is discussing the possibility of a clinical trial of cannabinoids combined with radiation in humans. The findings have been published in the journal Molecular Cancer Therapeutics.
Chemotherapy is commonly used in cancer patients, although it prolongs the patient's life, but it produces significant side effects and causes great pain to the patient. The derivative of THC, dronabinol, has been used in clinical practice as an antiemetic drug. However, due to its hallucinogenic effect and easy addiction, its application is limited.
Parker et al. evaluated the anti-vomiting effect of CBD and its analogue CBD-DMH in conditional rejection models, and the results showed that CBD and CBD-DMH had anti-vomiting effects on mice. Because CBD toxicity is very small, it has a good application prospect for alleviating the nausea and vomiting reaction produced by patients after chemotherapy.
In July 2015, a study published in The Journal of Pain found that cannabis can reduce peripheral neuralgia in diabetic patients in a dose-dependent manner, confirming that industrial hemp CBD has a role in reducing the incidence of diabetes.
CBD also has antioxidant effects capable of fighting glutamate neurotoxins (stronger than the effects of ascorbates or vitamin E) and is a potential antioxidant. In addition, CBD also has anti-tranquilizer and anti-gram-positive effects; it is effective in controlling dystonia movement disorders and mechemia. CBD analogues △6-CBD have THC-like activity.