• Archives of Pharmacal Research
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• v.23 no.2
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• pp.121-127
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• 2000

Cannabigerol (1, CBG), methyl 4-[(2E)-3,7-dimethyl-2,6-octad ienyl)oxy]-3-methoxybenzoate (2, DTM), 5-fluorouracil (3, FU) as a reference, and cannabidiol (4, CBD) were tested for their growth inhibitory effects against KB(ATCC NO, OCL 17) cell lines using two different assays, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and the sulforhod-amine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of $IC_{50}$ values of these compounds in tumor cell lines showed that their susceptibility to these compounds decreases in the following order: DTM > CBD > 5-FU > CBG by MTT assay and DTM = CBD > 5-FU > CBG by SRB assay. CBG 1, DTM 2, 5-FU 3, and CBD 4 were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different assays, the MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 3T3 fibroblasts. In general, the cytotoxic acivities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentraion range of 1 to 100 M. The comparison of $CD_{50}$ values of these compounds in NIH 3T3 fibroblasts shows that their susceptibility to these compounds in decreases the following order(:) CBD > 5-FU > DTM > CBG by MTT assay, CBD > 5-FU > CBG > DTM by SRB assay. These results suggest that DTM 2 has the most growth-inhibitory activity against KB cell lines.

• 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.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1086-1091
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• 2005

An analytical method was developed for evaluating the cannabidiol (CBO), cannabinol (CBN), ${\Delta}^9-tetrahydrocannabinol$ $({\Delta}^9-THC)$ level in human hair using gas chromatography-mass spectrometry (GC-MS). Hair samples (50mg) were washed with isopropyl alcohol and cut into small fragments (< 1mm). After adding a deuterated internal standard, the hair samples were incubated in 1.0M NaOH for 10 min at $95^{\circ}C$. The analytes from the resulting hydrolyzed samples were extracted using a mixture of n-hexane-ethyl acetate (75:25, v/v). The extracts were then evaporated, derivatized, and injected into the GC-MS. The recovery ranges of CBD, CBN, and ${\Delta}^9-THC$ at three concentration levels were $37.9-94.5\%$ with good correlation coefficients $(r^2>0.9989)$. The intra-day precision and accuracy ranged from $-9.4\%\;to\;17.7\%$, and the inter-day precision and accuracy ranged from $-15.5\%\;to\;14.5\%$, respectively. The limits of detection (LOD) for CBD, CBN, and ${\Delta}^9-THC$ were 0.005, 0.002, and 0.006 ng/mg, respectively. The applicability of this method of analyzing the hair samples from cannabis abusers was demonstrated.

• 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 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.

• 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.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.6
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• pp.337-356
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• 2020

This systematic review focused on the efficacy of topical products in reducing temporomandibular joint disorder (TMD)-associated pain, in comparison to placebo or control interventions. The EMBASE, Web of Science, Cochrane Library, and MEDLINE via PubMed databases were searched for randomized controlled trials (RCTs) using topical interventions in adults diagnosed with TMD. The pain intensity was the primary outcome, and other clinical findings were the secondary outcomes. The risk of bias was evaluated according to the Cochrane's handbook. The search up to February 7, 2020 identified a total of 496 unduplicated references. Nine RCTs with 355 adult patients diagnosed with TMD were included. The meta-analysis did not show a significant reduction in baseline pain intensity in the nonsteroidal anti-inflammatory drug (NSAIDs) group, when compared to the placebo group (P = 0.288). One study demonstrated a statistically significant pain score decrease for Theraflex-TMJ compared to placebo after 10 d of treatment (P = 0.003) and follow-up, 5 d after the last application (P = 0.027). Ping On reduced pain at 4 weeks of application (P < 0.001) but not after 7 d of application (P = 0.136). In one study, cannabidiol (CBD) significantly improved the pain intensity compared to placebo (P < 0.001). However, no differences were found with capsaicin in the two studies (P = 0.465). Evidence was of low quality because the studies were considered as having an unclear or a high risk of bias and a small number of studies were analyzed. The evidence is not sufficient to support the use of topical NSAIDs and capsaicin, and limited evidence was found for Threraflex-TMJ, bee venom, Ping On, and CBD, with only one study reporting for each. Additional studies are recommended to validate these results.

• 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.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.51 no.5
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• pp.483-490
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• 2006

In order to breed hemp variety with nondrug type adapted to Korea, a total of 44 accessions were introduced from Center for plant breeding and reproduction research (CPRO) In Netherland and evaluated for plant growth characteristics and contents of cannabinoids such as tetrahydrocannbinol (THC), cannabidiol (CBD), Cannabinol (CBN) in Korean climatical and geographical condition. 1. In Korean geographical position which latitude is $34^{\circ}N$, days to flowering and stem length were shorter than in Netherlands which latitude is $52^{\circ}N$. But THC content was not shown significant difference between two areas. 2. Corrected accessions of hemp were classified into 3 variety groups by cluster analysis and 4 accessions including Korean local variety were not classified into any variety group. 3. Most hemp accessions have low THC contents but were not suitable for fiber production in Korea due to short days to flowering and stem length. 4. Among the introduced accessions, IH3 was suitable for breeding material of fiber hemp with non-drug type because of low THC content and similar days to flowering with Korean local variety.