• Journal of Pharmacopuncture
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• v.24 no.2
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• pp.68-75
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• 2021

Objectives: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/β-catenin signaling pathway. We are to investigate β-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. Methods: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by β-catenin expression using RT-PCR and immunostaining experiment. Results: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of β-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that β-catenin expression is a key regulatory function during alopecia progression. Consistently, β-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that β-catenin expression was decreased in RNA level, as well as decreased β-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including β-catenin, but the decreased β-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. Conclusion: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

• Journal of Dental Anesthesia and Pain Medicine
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• v.21 no.6
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• pp.479-506
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• 2021

Background: Chronic neuropathic pain (NP) presents therapeutic challenges. Interest in the use of cannabis-based medications has outpaced the knowledge of its efficacy and safety in treating NP. The objective of this review was to evaluate the effectiveness of cannabis-based medications in individuals with chronic NP. Methods: Randomized placebo-controlled trials using tetrahydrocannabinol (THC), cannabidiol (CBD), cannabidivarin (CBDV), or synthetic cannabinoids for NP treatment were included. The MEDLINE, Cochrane Library, EMBASE, and Web of Science databases were examined. The primary outcome was the NP intensity. The risk of bias analysis was based on the Cochrane handbook. Results: The search of databases up to 2/1/2021 yielded 379 records with 17 RCTs included (861 patients with NP). Meta-analysis showed that there was a significant reduction in pain intensity for THC/CBD by -6.624 units (P < .001), THC by -8.681 units (P < .001), and dronabinol by -6.0 units (P = .008) compared to placebo on a 0-100 scale. CBD, CBDV, and CT-3 showed no significant differences. Patients taking THC/CBD were 1.756 times more likely to achieve a 30% reduction in pain (P = .008) and 1.422 times more likely to achieve a 50% reduction (P = .37) than placebo. Patients receiving THC had a 21% higher improvement in pain intensity (P = .005) and were 1.855 times more likely to achieve a 30% reduction in pain than placebo (P < .001). Conclusion: Although THC and THC/CBD interventions provided a significant improvement in pain intensity and were more likely to provide a 30% reduction in pain, the evidence was of moderate-to-low quality. Further research is needed for CBD, dronabinol, CT-3, and CBDV.

• YAKHAK HOEJI
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• v.17 no.1
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• pp.21-26
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• 1973

The constituents of Korean cannabis were studied comparatively with foreign orgins. Especially, tetrahydrocannabinol(THC), the active constituents of cannabis were analyzed by the technique of thin layer chromatography and colorimetry. The results are as follows ; (1) THC content in Korean cannabis is comparatively higher than that in foreign samples. (2) THC is contained most abundantly in male flowers, abundantly in female tops and leaves and some in barks. (3) There is a tendency that the THC content increase gradually with growth of plants, being highest during unripe nad decrease with maturity of the tops. (4) Korean cannabis contains THC, cannabinol, cannabidiol, cannabidiolic acid and other cannandiolic compounds. Distribution of chemical components of Korean cannabis, compared with those of foreign ones, is remarkably different. (5) The THC content of Spanish cannabis cultivated tentatively in Korea is similar to that of Korean cannabis.

• Journal of Life Science
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• v.31 no.7
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• pp.677-685
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• 2021

Cannabis sativa L. belongs to the Cannabaceae family and is an annual herbaceous flowing plant. The plants can be classified into narcotic marijuana and nonnarcotic hemp. Different parts of C. sativa L. have been used as food, medicine, cosmetics, fiber and textile. However, the use of leaf, flower, and seed of C. sativa L was forbidden in Korea in January 1977 as a result of the Cannabis Control Act due to the narcotic properties. The plant's mature stems have limited uses for the production of fiber and sheets. Recently, various cannabinoids, terpenes and essential fatty acids were identified from C. sativa L., and their safety and useful bio-activities, such as neuroprotective, anti-inflammation, antithrombosis, antiepileptic, and antimicrobial activities, and the relief of pain, have been highlighted. Furthermore, the process of reduction of tetrahydrocannabinol, a representative narcotic compound, and the isolation of cannabidiol, a nonnarcotic active compound in C. sativa L., have been determined. These findings resulted in the legalization of C. sativa L. in Korea for medical use in December 2018 and the exclusion of C. sativa L. from the narcotic list of the UN Commission on Narcotics Drugs (UNCND) in December 2020. Therefore, developments of various high-value added products have commenced worldwide. Additionally, in 2021, the Korean government deregulated special zones based on hemp. In this study, the current status and the prospect of the hemp industry, as well as essential techniques for developing new hemp products, are provided for the activation of the Korea Green-Rush.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.225-230
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• 2019

Objectives: This study was to discuss the research trend of dementia treatment using cannabis for the purpose of providing the basis of cannabis use for medical purposes in the future. Methods: This study searched publications, which were registered to databases or published by Aug 22, 2019, and targeted the full-text or abstracts of these publications. We selected the final nine studies met all selection criteria. Results: These results implied that the CBD components of cannabis might be useful to treat and prevent AD because CBD components could suppress the main causal factors of AD. Moreover, it was suggested that using CBD and THC together could be more useful than using CBD or THC alone. Conclusion: We hope that there will be a solid foundation to use cannabis for medical use by continuously evaluating the possibility of using cannabis for clinical purposes as a dementia treatment substance and cannabis can be used as a positive tool.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1365-1375
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• 2005

The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., $\bigtriangleup^{9}$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-O­deethylase (EROD) assay, the aromatase assay, and the 17$\beta$-estradiol ($E_{2}$) metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the $E_{2}$ metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ $E_{2}$ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.124-124
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• 2022

대마(Cannabis sativa)는 카나비노이드(cannabinoids) 계열의 성분으로 인한 약리효능 뿐만 아니라 섬유, 식품 등의 분야에서도 식물소재로 활용도가 높은 것으로 알려져 있다. 최근 의료용 대마의 경우 규제완화가 예정됨에 따라 관련 산업분야에서도 안정적 원료 소재 생산에 대한 연구가 요구되고 있다. 대마는 실생번식이 가능한 종이나, 의료용 등 소재의 안정적 공급을 위해서는 균일한 cannabidiol(CBD) 성분의 확보가 가능한 영양증식 방법이 대안으로 사용될 수 있다. 따라서 본 연구에서는 영양증식 방법 중 조직배양 기술을 이용한 대마 품종별(Cherry Blossom, Queen Dream과 Hot Blonde) 증식법 구명을 위하여 식물생장조절제의 종류 및 농도에 따른 기내생육특성을 조사하였다. 세 품종 모두 1 mg l^-1 thidiazuron (TDZ) 단독처리 시 신초(> 2cm)가 가장 많이 유도되었다. 단 Queen Dream 품종은 0.5 mg l^-1 와 TDZ 0.2 mg l^-1 NAA 혼용처리구에서 많은 수의 신초가 유도되었으나 상대적으로 신초의 길이(< 2cm)는 짧은 것으로 확인할 수 있었다. 발생된 신초는 MS 기본배지에서 발근을 유도한 후 토양에 순화하여 정상적인 식물체로 발달되었다. 이와 같은 식물생장조절제 처리를 포함한 식물조직배양 방법은 유용 개체·품종의 증식 및 의료·산업용 원료 소재의 안정적 생산에 활용될 수 있다.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.194-199
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• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.682-688
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• 2020

Hemp (Cannabis sativa L.) is a dioecious plant, although monoecious plants are bred in some cultivars for fiber or seed production. Recently, hemp has received attention for medicinal use with some cannabinoids, including cannabidiol. Self-fertilization for breeding inbred lines is difficult because of dioeciousness and anemophily in hemp. This experiment was conducted to develop a self-fertilization method by forming female flowers and seeds from male plants of dioecious hemp. To induce the formation of female flowers on male plants, 500 mg L^-1 of ethephon was sprayed on plants at soon, seven and fourteen days after primordia formation. The plant ratio of female flowers formation and the number of harvested seeds were increased by ethephon treatment. Female flowers of male plants have 5 stigmas in contrast to the dual stigma of female 1plants. Male plant seeds were lighter and smaller than those from female plants. Although the germination rate was lower than that of normal seeds from female plants, the seeds from male plants germinated to grow seedlings. Thus, we suggest that hemp plants should be treated with ethephon at soon after primordia formation to induce the formation of more female flowers on the male plants.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.57-64
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• 2007

Metabolic interactions of the three major cannabinoids, ${\Delta}^9$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) with steroid hormones were investigated. These cannabioids concentration-dependently inhibited $3{\beta}$-hydroxysteroid dehydrogenase and $17{\alpha}$-hydroxylase in rat adrenal and testis microsomes. CBD and CBN were the most potent inhibitors of $3{\beta}$-phydroxysteroid dehydrogenase and progesterone $17{\alpha}$-hydroxylase, respectively, in rat testis microsomes. Three cannabinoids highly attenuated hCG-stimulated testosterone production in rat testicular interstitial cells. These cannabinoids also decreased in levels of mRNA and protein of StAR in the rat testis cells. These results indicate that the cannabinoids could interact with steroid hormones, and exert their modulatory effects on endocrine and testicular functions. Metabolic interaction of a THC metabolite, $7{\beta}$-hydroxy-${\Delta}^8$-THC with steroids is also investigated. Monkey liver microsomes catalyzed the stereoselective oxidation of $7{\beta}$-hydroxy-${\Delta}^8$-THC to 7-oxo-${\Delta}^8$-THC, so-called microsomal alcohol oxygenase (MALCO). The reaction is catalyzed by CYP3A8 in the monkey liver microsomes, and required NADH as well as NADPH as an efficient cofactor, and its activity is stimulated by some steroids such as testosterone and progesterone. Kinetic analyses revealed that MALCO-catalyze reaction showed positive cooperativity. In order to explain the metabolic interaction between the cannabinoid metabolite and testosterone, we propose a novel kinetic model involving at least three binding sites for mechanism of the metabolic interactions.