• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• 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.

• 대한예방한의학회지
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• 제2권1호
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• pp.13-30
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• 1998

제라니올 (1), 올리비톨 (2), 카나비노이드 (3 과 4)와 5-플로르우라실 (5)을 MTT 정량분석법과 SRB 정량분석법으로 인체 피부흑색종세포에 대하여 성장 억제효과를 평가 하였다. 이들 화합물(1, 2, 3, 4와 5)은 마이크로 몰 농도의 범위에 대하여 억제 활성을 나타내었다. 일반적으로 이들 화합물은 $1{\mu}M\;-\;100{\mu}M$ 농도범위에서는 투여량에 따라 항암활성을 나타내었다. 인체 피부흑색종세포에 대한 이들 화합물의 50 %억제 농도 효과에 대한 비교는 다음과 같은 순서로 항암활성이 감소하였다. MTT 정량분석법 ; OLVTL >CBG > CBD > 5-FU >GRNL, SRB 정량 분석법 ; CBG > OLVTL > CBD > CRNL > 5-FU, 카나비노이드 (3 과 4)와 5-플로르우라실 (5)을 MTT정량분석법과 SRB정량분석법으로 인체정상세포에 대하여 독성효과를 측정하였다. 이들 화합물은 마이크로몰농도의 농도범위에서는 투여량에 따라 세포독성을 보였다. 인체정상세포에 대한 이들 화합물의 50 % 독성효과에 대한 비교는 다음과 같은 순서로 세포독성이 감소하였다. MTT정량분석법과 SRB정량분석법 ; CBD > 5-FU > CBG. 따라서 카나비지놀 (3)은 인체정상세포에 대하여 가장 낮은 세포독성을 나타내었다. 따라서 카나비지놀 (3)은 인체 피부흑색종세포에 대하여 가장 강한 성장억제활성을 보였다.

• 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.

• 한국자원식물학회지
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• 제33권6호
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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.

• Molecular & Cellular Toxicology
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• 제2권4호
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• pp.223-228
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• 2006

Several plant-derived cannabinoids and endogenous ligands for cannabinoid receptors such as 2-arachidonyl-glycerol have been known to inhibit interleukin-2 (IL-2) expression. In the present study, we utilized arachidonylethanolamide (AEA), a putative endogenous ligand for cannabinoid receptors, to determine whether AEA modulated the expression of IL-2. AEA inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced IL-2 protein secretion and mRNA expression in EL-4 mouse T-cells as determined by ELISA and RT-PCR, respectively. To further characterize the inhibitory mechanism of AEA at the transcriptional level, we performed promoter study for IL-2 gene in PMA/Io-stimulated EL-4 cells. AEA decreased the transcriptional activity of the nuclear factor of activated T-cells (NF-AT) as well as the IL-2 promoter activity. These results suggest that AEA suppresses IL-2 expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT.

• Archives of Pharmacal Research
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• 제21권3호
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• pp.353-356
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• 1998

Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) and NIH 3T3 fibrobalsts using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. Cannabigerol (3) exhibited the highest growth-inhibitory activity against the cancer cell lines.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.363-369
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• 2014

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the $CB_1$ receptor (JWH-073, 081, and 210) and ${\Delta}^9$-tetrahydrocannabinol (${\Delta}^9$-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. $K_i$ values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed $CB_1$ protein membranes to compare dependence potential with $CB_1$ receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except ${\Delta}^9$-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the $CB_1$ receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.266-271
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• 2017

Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

• 생명과학회지
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• 제31권7호
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• pp.677-685
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• 2021

대마(Cannabis sativa L.)는 삼과에 속하는 1년생 초본식물로, 바람에 의해 수정되는 풍매화이면서 자웅이주식물이다. 대마는 중독성 마리화나와 비중독성 헴프로 구분 가능하다. 대마는 인류 역사와 가장 밀접한 관련성을 가진 식물 중 하나로, 과거로부터 다양한 부위를 식용, 약용, 화장품, 섬유, 생활용품 등으로 이용하여 왔다. 그러나 대마꽃, 잎, 종실 등에 포함된 중독, 환각 성분으로 인해, 국내에서는 1977년 1월부터 시행한 [대마관리법]에 의거하여, 대마 줄기를 이용한 섬유산업 이외에는 실질적인 연구 및 산업화가 진행되지 못하였다. 최근 대마로부터 400여종의 cannabinoids 물질, terpene 및 필수지방산 등이 확인되고, 이들의 신경세포 보호, 항염증, 항혈전, 항균, 통증완화 및 뇌전증 치료 등의 유용 생리활성이 알려지고, 테트라히드로칸나비놀(tetrahydrocannabinol)로 대표되는 환각 중독성 물질의 제거 및 저감화, 비환각성 물질의 분석, 정제 기술이 빠르게 보고되면서 2018년 12월 국내 의료용 대마의 합법화 및 2020년 12월 UN 마약위원회의 대마와 대마수지의 마약목록 삭제가 확정되었다. 따라서 국내외에서 대마의 다양한 부위를 이용한 고부가가치 식품, 화장품, 의약품 개발이 시작되고 있다. 본 보에서는 국내 2021년 헴프 기반의 바이오산업 규제자유특구 지정과 함께, 국내 대마생물산업의 현황과 대마산업 활성화를 위한 필수기술, 향후 전망을 제시하여 국내 대마 생물산업의 발전방안을 제시하고자 하였다.