• Journal of Dental Anesthesia and Pain Medicine
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• 제21권6호
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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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• 제28권9호
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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.

• 대한약침학회지
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• 제22권4호
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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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• 제28권12호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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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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• 제20권6호
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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.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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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.

• 한국작물학회지
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• 제51권5호
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• pp.483-490
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• 2006

저 마약형 대마 품종 육성에 이용하고자 네덜란드 CPRO에서 도입한 저 마약형 유전자원의 특성을 검정한 결과는 다음과 같다. 1. 도입 유전자원들은 고위도인 네덜란드에서 재배했을 때에 비해 중위도인 우리나라에 재배했을 때 개화소요일수가 짧아 경장이 작았다. CBD 함량은 두 지역간 차이가 다소 있는 경향이었으나 THC 함량은 거의 변하지 않았다. 2. 개화소요일수, 경장, 경직경, 생경중 및 섬유수량 등 대마 생육형질들은 서로 간에 고도로 유의한 정의 상관을 보였고, cannabinolds 함량과의 상관에서는 CBD 함량과는 고도로 유의한 정의 상관을 보였으나 THC와 CBN 함량과는 유의한 상관관계를 보이지 않았다. 3. 공시한 44 도입종과 재래종을 군집분석의 Q 상관으로 도출된 r = 0.80으로 선을 그었을 때 3개 품종군으로 나누어졌으며 품종군에도 속하지 않는 것이 4품종이었다. 4. 분류된 모든 품종군은 개화소요일수와 경장이 짧아 우리나라에서 섬유용 품종으로 적합하지 않았고 품종군으로 분류되지 않은 것들 중 도입종 IH3은 THC 함량이 0.08%로 낮으면서 개화소요일수가 122일로 재래종과 비슷하였다.

• 한국작물학회지
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• 제51권3호
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• pp.187-190
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• 2006

저 마약형 대마 품종이 육성되지 않았을 경우 그 대안으로서 섬유용 대마의 THC 함량을 낮추기 위해 저 마약형 도입 유전자원중 경장은 작지만 개화기가 재래종과 비슷한 IH3 과 재래종 종자를 1:1, 2:1, 3:1로 혼합하여 채종시험을 실시하고 각 혼합비율별로 채종한 종자를 섬유용으로 재배하여 종실용 및 섬유용 대마 생육특성과 수량, 그리고 cannabinoid 함량분포를 검정한 결과를 요약하면 다음과 같다. 채종시험에서 IH3 의 비율이 클수록 천립중은 무거웠으나 종실수량은 100 kg/10a 내외로 차이가 없었다. 혼합비율별로 집단 채종한 종자를 섬유용으로 재배하였을 때 섬유수량은 $193{\sim}198kg/10a$로 비슷하였으나 THC 함량은 종자 IH3 혼합비율이 클수록 낮아져 3:1 에서는 0.39%이었다. THC 및 CBD 함량분포에서도 IH3 혼합비율이 높을수록 마약형 및 중간형 비율이 낮아졌고 저 마약형 비율은 증가하였다.