• Title/Summary/Keyword: Cannabinoids

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Development of New Surfaces and Materials for Separation Science

  • Linford, Matthew R.
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.59.1-59.1
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    • 2015
  • In the Linford group at Brigham Young University we have recently developed three new sets of materials for three different areas of separations science: thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and solid phase microextraction (SPME). First, via microfabrication we have grown patterned carbon nanotube (CNT) forests on planar substrates that we have infiltrated with inorganic materials such as silicon nitride. The coatings on the CNTs are conformal and typically deposited in a process like low pressure chemical vapor deposition. The resulting materials have high surface areas, are porous, and function as effective separation devices, where separations on our new TLC plates are typically significantly faster than on conventional devices. Second, we used the layer-by-layer (electrostatically driven) deposition of poly (allylamine) and nanodiamond onto carbonized poly (divinylbenzene) microspheres to create superficially porous particles for HPLC. Many interesting classes of molecules have been separated with these particles, including various cannabinoids, pesticides, tricyclic antidepressants, etc. Third, we have developed new materials for SPME by sputtering silicon onto cylindrical fiber substrates in a way that creates shadowing of the incoming flux so that materials with high porosity are obtained. These materials are currently outperforming their commercial counterparts. Throughout this work, the new materials we have made have been characterized by X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, scanning electron microscopy, transmission electron microscopy, etc.

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Fluorescence-based Assay System for Endocannabinoid Degradation Enzyme, Fatty Acid Amide Hydrolase

  • Kim, Dae-Woong;Kim, Gun-Joong;Kim, Hae-Jo;Ghil, Sung-Ho
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.279-285
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    • 2010
  • Endogenous cannabinoids (endocannabinoids) display various pharmacological effects including pain control, anti-inflammation, and neuroprotection. The synthesis and release of endocannabinoids are regulated under both physiological and pathological conditions. The main degrading enzyme of endocannabinoid is fatty acid amide hydrolase (FAAH). Therefore we have developed the fluorescence-based assay system for FAAH. We established stable CosM6 cell lines expressing human FAAH. We also synthesized 2-oxo-2H-chromen-7-yl decanoate (DAEC) as a fluorogenic substrate for FAAH. When crude membrane extracts stably expressing FAAH was incubated with DAEC at $25^{\circ}C$, FAAH reacted specifically to DAEC and catalyzes the hydrolysis of DAEC into decanoic acid and highly fluorescent coumarin. Furthermore, the serin hydrolase inhibitor, phenylmethanesulfonylfluoride, inhibited the coumarin release to the reaction buffer in concentration dependent manner. This assay system is suitable for high-throughput screening since this system has simple experimental procedure and measurement method.

Understanding of Medical Cannabis and its Regulations: A Suggestion for Medical and Scientific Needs (의료용 대마(大麻)의 이해 및 법적 규제에 대한 고찰: 대마의 치료적, 학술적 필요성 제고)

  • Han, Kyungsun;Lee, Myeong-Jong;Kim, Hojun
    • Journal of Korean Medicine for Obesity Research
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    • v.16 no.2
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    • pp.124-132
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    • 2016
  • In traditional medicine, Cannabis sativa L. has been used for variety of reasons. Old literatures delineate that Cannabis had been used as anesthetic and analgesic, or to reduce symptoms such as cough, paralysis and so on. Although Cannabis has a long history of medical use, it is illegal in many countries including South Korea. Controversy over decriminalization of Cannabis to allow cannabis for therapeutic use has been around for many years. In order to understand current knowledge on the therapeutic use of medical Cannabis, comprehension of cannabinoids and other constituents of Cannabis is important. Here we reviewed the pharmacological effect of Cannabis and current mandatory regulation over Cannabis in many countries to suggest necessity of research on medical Cannabis.

SR144528 as Inverse Agonist of CB2 Cannabinoid Receptor

  • M.H. Rhee;Kim, S.K.
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.96-96
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    • 2002
  • We examined the role of SR 144528 (N-[-(1S-endo-1,3,,3-trimethyl-bicycle[2, 2, 1 ] heptan-2-y1]-5-(-4-chloro-3-mothyl-phenyl)-(4-methylbenzyl)-pyrazole-3- carboxamide) in the modulation of certain AC isoforms in transiently transfected COS-7 cells. We found that CB2 in COS cells has a constitutive activity, and thus leading to inhibition of AC-V activity even in the absence of agonist. In addition, this constitutive modulation of AC is reversed by SR144528. It is now well established that several G protein-coupled receptors can signal without agonist stimulation(constitutive receptors). Inverse agonists have been shown to inhibit the activity of such constitutive G protein-coupled receptor signaling. Agonist activation of the G$\_$i/o/-coupled peripheral cannabinoid receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl cyclase type II. Using transfected COS cells, we show here that application of SR144528, an inverse agonist of CB2, leads to a reverse action (stimulation of adenylyl cyclase V and inhibition of adenylyl cyclase II). This inverse agonism of SR144528 is dependent on the temperature, as well as on the concentration of the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl cyclase activity by SR 144528.

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Effects of Plant Growth Regulators for In Vitro Propagation of Cannabis sativa varieties (대마 품종별 기내 증식을 위한 식물생장조절제 처리 효과)

  • Hyunseok Lee
    • 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.

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Experimental Studies on the Anti-inflammatory Effect of Cannabis sativa based on a Scientometric Analysis

  • Eunsoo Sohn;Sung Hyeok Kim;Sohee Jang;Se-Hui Jung;Kooyeon Lee;Eun-Hwa Sohn
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.45-45
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    • 2021
  • This study aimed to explore research on bibliometric features of cannabis by applying scientometric analysis method, and to approach experimental research evaluation based on it. A total of 30,352 articles on cannabis published since 2001 from SCOPUS were analyzed using KnowledgeMatrix Plus and VOSviewer software. Results showed differences in research activities in countries where cannabis is legalized (Canada, the United States, the Netherlands) and Asian countries where its use is illegal. Related to medical cannabis, there has been a noticeable increase in the number of studies on pain, epilepsy, seizures and brain diseases such as multiple sclerosis. In the field of basic research, the number of pharmacological studies of cannabis on the cannabinoid type 1 receptor signaling pathway and inflammation and obesity has increased significantly. Subsequent experimental studies have compared the anti-inflammatory effects of four parts of Korean cannabis such as root, stem, leaf, and bark. Consistent with the predicted results of the scientometric analysis, all parts of C. sativa showed inhibitory effects on COX-2, NO/iNOS and TNF-α expression in LPS-stimulated RAW264.7 cells. These attempts provide an experimental research approach based on scientometric assessment.

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Metabolic Activation of Marijuana Constituents, Cannabinoids, in Relation to Their Toxicity for Human and Its Oxidation Mechanism

  • Ikuo, Yamamoto
    • 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.

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A role for endocannabinoids in acute stress-induced suppression of the hypothalamic-pituitary-gonadal axis in male rats

  • Karamikheirabad, Maryam;Behzadi, Gila;Faghihi, Mahdieh;Raoofian, Reza;Mehr, Shahram Ejtemaei;Zuure, Wieteke Ameliek;Sadeghipour, Hamid Reza
    • Clinical and Experimental Reproductive Medicine
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    • v.40 no.4
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    • pp.155-162
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    • 2013
  • Objective: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. Methods: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 ${\mu}g/rat$). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. Results: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. Conclusion: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.

Efficacy of cannabis-based medications compared to placebo for the treatment of chronic neuropathic pain: a systematic review with meta-analysis

  • Sainsbury, Bradley;Bloxham, Jared;Pour, Masoumeh Hassan;Padilla, Mariela;Enciso, Reyes
    • 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.

Cluster Analysis and Growth Characteristics of Hemp (Cannabis sativa L.) Germplasm (저 마약형 대마 유전자원의 생육특성 및 품종군 분류)

  • Moon Youn-Ho;Song Yeon-Sang;Jeong Byeong-Choon;Bang Jin-Ki
    • 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.