Phytocannabinoids are bioactive terpenoids that are exclusive to Cannabis sativa L. The main pharmacologically active phytocannabinoids are Δ9-tetrahydrocannabinol and cannabidiol, both target endogenous cannabinoid receptors. Δ9-tetrahydrocannabinol and cannabidiol have extensive therapeutic potential due to their participation in many physiological and pathological processes in human body by activating the endocannabinoid system. At present, Δ9-tetrahydrocannabinol, cannabidiol and their analogues or combination preparations are used to treat epilepsy, vomiting in patients with cancer chemotherapy, spasticity in multiple sclerosis and relieve neuropathic pain and pain in patients with advanced cancer. With the further exploration of the application value of Δ9-tetrahydrocannabinol and cannabidiol as well as the increasing demand for standardization of pharmaceutical preparations, it is imminent to achieve large-scale production of Δ9-tetrahydrocannabinol and cannabidiol in the pharmaceutical industry. In this article, pharmacological research progress of phytocannabinoids in recent years, biosynthetic pathways of phytocannabinoids and the mechanism of key enzymes as well as various product development strategies of cannabinoids in pharmaceutical industry are reviewed. By exploring the potential of synthetic biology as an alternative strategy for the source of phytocannabinoids, it will provide a theoretical basis for the research and development of microbial engineering for cannabinoids synthesis, and promote the large-scale production of medicinal cannabinoids.
Cannabidiol ; Cannabinoids/biosynthesis* ; Cannabis ; Humans ; Receptors, Cannabinoid

The shortage of new cannabis varieties with low THC and high CBD content and irregular planting techniques have become the bottleneck for he development of non-psychoactive medicinal cannabis industry. Based on the cannabis germplasm resources,this paper proposes strategies for breeding high CBD content,seed-type and high-efficiency,dwarf non-psychoactive medicinal cannabis varieties through molecular marker development,assisted breeding,genetic engineering breeding and traditional breeding. According to the suitable ecological factors of non-psychoactive medicinal cannabis,the CBD content and grain yield of non-psychoactive medicinal cannabis can be improved by regulating the nutritional structure and illumination properties of non-psychoactive medicinal cannabis,scientific harvesting and storage. At the same time,in order to further accelerate the application of non-psychoactive medicinal cannabis,we can accelerate the selection of new varieties of non-psychoactive medicinal cannabis by mining genetic information of cannabis,and strengthen the application of information technology and automation of modern agriculture in the production of non-psychoactive medicinal cannabis. Provide basis for the cultivation and wide application of new non-psychoactive medicinal cannabis varieties with high quality and high yield.
Agriculture ; Cannabidiol/analysis* ; Cannabis ; Medical Marijuana

Cannabis sativa,with a long history of cultivation, is a traditional industrial crop widely used for food, textiles, and me-dicine. This study discussed industrial C. sativa and medicinal C. sativa. According to the characteristics of management policies of C. sativa in different periods, we divided the development stages of C. sativa into three stages and analyzed the changes in breeding and cultivation goals under the influence of policies. Meanwhile, a comprehensive analysis was carried out based on the breeding conditions of industrial C. sativa in China. Because of the vast territory of China, the differences in agricultural planting environment, economic development, and social development in the southern and northern areas result in different used parts of C. sativa. To be speci-fic, flowers and leaves are used in Yunnan, fiber in Heilongjiang, and seeds in Shanxi. The breeding of C. sativa varieties highlights fiber, seeds, or both of them. As the value of cannabidiol is explored, medicinal C. sativa has been approved in recent years. Based on the cultivation characteristics and value of industrial C. sativa, it is proposed that industrial C. sativa has a broad application prospect as an important industrial crop, and the existing products contain almost no tetrahydrocannabinol. The cultivation of C. sativa should be rationally guided to promote the development of the C. sativa industry. Moreover, it is recommended to actively apply advanced breeding techniques such as molecular breeding to overcome the problems of the uncertainty of the existing induced breeding and the excessively long hybrid breeding cycle, and develop high value-added applications such as medicinal products of C. sativa to enhance the exploitation of the economic value of C. sativa.
Cannabidiol/analysis* ; Cannabis/genetics* ; China ; Dronabinol ; Plant Breeding

OBJECTIVES: To establish a high performance liquid chromatographic （HPLC） method for simultaneous determination of three effective constituents, including tetrahydrocannabinol （THC）, cannabidiol （CBD） and cannabinol （CBN） in Cannabis plants. METHODS: A C₁₈ column was used in this study, and acetonitrile-phosphate buffer （0.015 mol/L KH₂PO₄） was used as mobile phase at a flow rate of 1.0 mL/min. At a detection wavelength of 220 mm, UV absorption spectra were collected at the wavelength range of 190-400 nm, and the spectra and retention time were counted as qualitative evidence. RESULTS: THC, CBD and CBN could be well separated by this method. Three components had good linear relationship in the range of 0.4-40 μg/mL （R²≥0.999 3）. The recoveries were over 87%. The limits of detection were 1.8 ng, 2.0 ng and 1.3 ng, respectively. The relative standard deviation （RSD） were less than 5% for both inter-day and intra-day precisions. CONCLUSIONS Reversed-phase HPLC method is simple, rapid and accurate, and it is suitable for the qualitative and quantitative detection of THC, CBD and CBN in Cannabis plants.
Cannabidiol/analysis* ; Cannabinol/analysis* ; Cannabis/chemistry* ; Chromatography, High Pressure Liquid ; Dronabinol/analysis*

Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.
Humans ; Cannabidiol/therapeutic use* ; Neuroprotection ; Cannabinoids/therapeutic use* ; Epilepsy/drug therapy* ; Cannabis ; Neuroprotective Agents/therapeutic use*

Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.
Animals ; Cannabidiol/pharmacology* ; Cell Differentiation ; Depression/prevention & control* ; Hippocampus/metabolism* ; Humans ; Mice ; Neural Stem Cells ; Neurogenesis/physiology*

With the recent legalization of recreational cannabis in Canada and 11 states of the U.S., the interest surrounding cannabis use is increasing. However, many people and even clinicians in Korea do not have exact knowledge about the psychiatric consequences of cannabis use. In this narrative review, the characteristics of cannabis, the endocannabinoid system, and the psychiatric consequences of cannabis use were provided. Cannabis contains more than 80 cannabinoids in the native plant. Psychotropic properties of Δ-9-tetrahydrocannabinol and cannabidiol are most well studied. The two main receptors are cannabinoid-1 receptor and cannabinoid-2 receptor. Several endocannabinoids, such as anandamide and 2-arachidonoylglycerol, act on the receptors as the endogenous ligands. Cannabis influences mood, cognitive functions, and psychomotor functions in acute phase responses, increasing the odds ratio for motor vehicle crashes. Long-term cannabis use is associated with various psychotic outcomes, including the development of schizophrenia, although there is interindividual variability. Cannabis adversely influences learning, memory, and attention. More frequent, persistent, and earlier onset cannabis use is associated with greater cognitive impairment. The chronic cognitive effects of cannabis are complex and controversial. Cannabis has addictive potential, and cannabis use disorder is common. Clinicians should have evidence-based knowledge about the consequences of cannabis use and communicate accurate information about cannabis use and its associated risks to the public.
Canada ; Cannabidiol ; Cannabinoids ; Cannabis ; Cognition ; Cognition Disorders ; Endocannabinoids ; Korea ; Learning ; Ligands ; Marijuana Abuse ; Memory ; Motor Vehicles ; Odds Ratio ; Plants ; Psychoses, Substance-Induced ; Schizophrenia