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Assessment of the abuse liability of endogenous cannabinoid and synthetic cannabinoid agonists

Title
Assessment of the abuse liability of endogenous cannabinoid and synthetic cannabinoid agonists
Authors
윤경화
Issue Date
2016
Department/Major
대학원 의과학과
Publisher
이화여자대학교 대학원
Degree
Master
Advisors
오세관
Abstract
The emergence and use of synthetic cannabinoids have greatly increased in recent. These drugs are easily prevailed over the internet and on the streets. So it is easy to take these drugs to the citizens to enjoy feel high. Some synthetic cannabinoids were shown to abuse liability and were subsequently regulated by authorities. Since these drugs produces euphoric and hallucinogenic effects, they have been distributed illegally since late 2000 calling street names such as “Spice”, “Smoke” and “K2”. However, some compounds are not regulated appropriately due to the lack of abuse liability information. In the present study, the abuse liability of various cannabinoids, namely 2-AG, DEA, Noladin ether, Arvanil, AM1172, BAY, CB13, Lylamine, RVD-Hpa, Hemopressin, PF514273, AKB-48, APICA, AM1248, AM2233, AEA, AM281, JWH-030, JWH-175 and JWH-176 were studied to evaluate the potency of drug dependence with endogenous cannabinoid agonists which were used to know how they works through RT-PCR and western blot assay in the PC 12 cell line (Pheochromocytoma cell line). The abuse liability of these drugs was evaluated in vitro test and in vivo test. Especially, JWH-series compounds were selected to test in animal models for assessing the abuse potential of the drugs through the conditioned place preference (CPP) test. After the CPP test, these animal’s brains were selected for the Western-blot assay. Results showed that JWH-176 had some drug dependency at the dose 0.05mg/kg in the mice model. And other cannabinoid agonists increased the levels of TH mRNA and DAT mRNA, however, the level of CB1 receptor mRNA were not seen same pattern. Endogenous cannabinoids were really hard to know their ability of abuse because their effects on PC 12 cell line were not noticeable. The synthetic cannabinoid agonist’s drug abuse potentiation was stronger than endogenous cannabinoid’s effect on drug dependency. Therefore, these compounds have to be regulated by govern authorities as illicit drugs. These studies might play a role in the drug abuse regulation and give useful information to understand the action mode in dependence.;최근에 합성 대마류 약물들이 많이 시판되기 시작했다. 이러한 약물들은 인터넷이나 길거리에서 판매될 수 있다. 쉽게 이러한 약물들에 접근할 수 있기 때문에 시민들이 마약 중독에 쉽게 노출 되어 질 수 있다. 몇몇 대마류 약물들은 약물남용의 위험성 때문에 정부당국에 의해서 규제 되고 있다. “Spice”, “Smoke”, “K2”라고 불려지는 대마류 약물들은 2000년대 후반에 많이 유통되기 시작했다. 그러나 새롭게 합성된 대마류에 대한 적절한 규제가 없어서 통제하기가 어려운 실정이다. 왜냐하면 신합성물질들의 특성을 파악한 정보가 없기 때문이다. 이번 연구의 목적은 다양한 종류의 대마약물들의 중독의존성을 평가하는 것이다. 사용된 약물은 2-AG, DEA, Noladin ether, Arvanil, AM1172, BAY, CB13, Lylamine, RVD-Hpa, Hemopressin, PF514273, AKB-48, APICA, AM1248, AM2233, AEA, AM281, JWH-030, JWH-175, JWH-176이다. RT-PCR과 웨스턴 블럿 어세이를 통해 약물 의존도를 평가하였다. PC12 세포를 사용하였다. 특별히 JWH 계열 약물들을 선택하여 동물실험을 진행하였다. 약물의 중독성 정도는 장소조건화 실험을 통해 평가하였다. 장소조건화 실험 후, 마우스의 뇌를 적출하여 웨스턴 블럿 어세이를 진행하였다. JWH-176 약물이 0.05mg/kg 농도에서 약물의존성을 보였다. 그리고 다른 신합성 대마류 약물들은 TH와 DAT의 mRNA의 발현량을 증가시켰다. 하지만 CB1의 mRNA의 발현량의 변화는 보이지 않았다. 내인성 대마약물들은 합성 대마약물들 보다는 중독 및 의존성이 낮은 것으로 평가되었다. 그러므로 신합성 대마약물들을 불법마약류로 규제해야 하며 이러한 연구가 그 규제에 도움이 될 것이라 본다.
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