Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure
Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure
复制标题
DOI：
10.1111/j.1476-5381.2009.00399.x
复制
发表时间：
2009-11-01
影响因子：
7.3
通讯作者：
McGregor, I. S.
中科院分区：
文献类型：
--
作者：
Gunasekaran, N.;Long, L. E.;McGregor, I. S.
背景和目的：Delta 9-tetrahydrocannabinol（THC）是大麻的主要精神活性成分，在脂肪组织中积累，长期储存。在这里，我们调查是否条件下，促进脂解可以释放THC从脂肪细胞产生增加血液中的THC.Experimental方法：在体外研究涉及新鲜分离的大鼠脂肪细胞与THC孵育前暴露于脂解剂促肾上腺皮质激素（ACTH）。一种补充的体内方法研究了食物剥夺和ACTH对连续10天重复注射THC（10 mg中心点kg-1）的大鼠中THC血液水平的影响。促肾上腺皮质激素或食物剥夺促进脂解是通过测量glycerol levels.Key results：ACTH增加THC预处理的脂肪细胞在体外培养基中的THC水平的指标。促肾上腺皮质激素也增强THC释放从脂肪细胞在体外时，从大鼠反复预处理THC在体内。最后，在体内ACTH暴露和24小时的食物剥夺都增强了THC及其代谢产物，（-）-11-去甲-9-羧基-三角洲9-四氢大麻酚（THC-COOH）在大鼠的血液中，已预先暴露于重复THC injections.Conclusions和影响：本研究表明，脂解增强释放THC从脂肪储存回到血液中。这表明了“再中毒”的可能性，即食物剥夺或压力可能会提高长期暴露于药物的动物的血液THC水平。进一步的研究将需要确认这是否会导致功能性影响，如认知功能受损或“闪回”。
Background and purpose:Delta 9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC.Experimental approach:In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg center dot kg-1) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels.Key results:ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections.Conclusions and implications:The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.