背景:大麻的作用被认为是由其成分与内源性大麻素系统之间的相互作用介导的。Delta-9-四氢大麻酚(THC)与中枢大麻素受体结合,而大麻二酚(CBD)可能会影响内源性大麻素的功能,而不会直接作用于大麻素受体。我们研究了THC与不同剂量的CBD共同给药对健康志愿者血浆内源性大麻素水平的影响。方法:在一个随机的,双盲,四臂交叉研究,健康志愿者(n=46)吸入含有10mgTHC加上0、10、20或30mgCBD的大麻蒸气,在四个实验会议中。疗程之间的中位时间为14天(IQR=20)。在吸入前采集血液样本,并在0-,5-,15-,吸入后90分钟。THC的血浆浓度,CBD,anandamide,2-花生四酰基甘油(2-AG),和相关的非大麻素脂质使用液相色谱-质谱法进行测量。结果:服用大麻引起血浆中anandamide浓度的急性增加(18.0%,0.042ng/mL[95CI:0.023-0.062]),和非大麻素乙醇酰胺,二十二碳四烯醚乙醇胺(DEA;+35.8%,0.012ng/mL[95CI:0.008-0.016]),油酰乙醇胺(+16.1%,0.184ng/mL[95CI:0.076-0.293]),和N-花生四酰基-L-丝氨酸(+25.1%,0.011ng/mL[95CI:0.004-0.017])(p<0.05)。CBD对anandamide的血浆浓度无明显影响,使用三种剂量中任何一种的2-AG或相关的非大麻素类脂。在四场会议上,阿南达胺和DEA的吸入前浓度逐渐下降,从0.254ng/mL[95CI:0.223-0.286]到0.194ng/mL[95CI:0.163-0.226],从0.039ng/mL[95CI:0.032-0.045]到0.027ng/mL[95CI:0.020-0.034](p<0.05),分别。讨论:THC诱导血浆中anandamide和非大麻素乙醇酰胺的急性升高,但没有证据表明这些作用受到CBD共同管理的影响.在较高剂量的CBD或长期给药后,这种作用可能是明显的。治疗前anandamide和DEA水平的逐步降低可能与反复暴露于THC或参与者对测试程序的焦虑程度降低有关,需要进一步调查。该研究在clinicaltrials.gov(NCT05170217)上注册。
Background: The effects of cannabis are thought to be mediated by interactions between its constituents and the endocannabinoid system. Delta-9-tetrahydrocannabinol (THC) binds to central cannabinoid receptors, while cannabidiol (CBD) may influence endocannabinoid function without directly acting on cannabinoid receptors. We examined the effects of THC coadministered with different doses of CBD on plasma levels of endocannabinoids in healthy volunteers. Methods: In a randomized, double-blind, four-arm crossover
study, healthy volunteers (n=46) inhaled cannabis vapor containing 10 mg THC plus either 0, 10, 20, or 30 mg CBD, in four experimental sessions. The median time between sessions was 14 days (IQR=20). Blood samples were taken precannabis inhalation and at 0-, 5-, 15-, and 90-min postinhalation. Plasma concentrations of THC, CBD, anandamide, 2-arachidonoylglycerol (2-AG), and related noncannabinoid lipids were measured using liquid chromatography-mass spectrometry. Results: Administration of cannabis induced acute increases in plasma concentrations of anandamide (+18.0%, 0.042 ng/mL [95%CI: 0.023-0.062]), and the noncannabinoid ethanolamides, docosatetraenylethanolamide (DEA; +35.8%, 0.012 ng/mL [95%CI: 0.008-0.016]), oleoylethanolamide (+16.1%, 0.184 ng/mL [95%CI: 0.076-0.293]), and N-arachidonoyl-L-serine (+25.1%, 0.011 ng/mL [95%CI: 0.004-0.017]) (p<0.05). CBD had no significant effect on the plasma concentration of anandamide, 2-AG or related noncannabinoid lipids at any of three doses used. Over the four sessions, there were progressive decreases in the preinhalation concentrations of anandamide and DEA, from 0.254 ng/mL [95%CI: 0.223-0.286] to 0.194 ng/mL [95%CI: 0.163-0.226], and from 0.039 ng/mL [95%CI: 0.032-0.045] to 0.027 ng/mL [95%CI: 0.020-0.034] (p<0.05), respectively. Discussion: THC induced acute increases in plasma levels of anandamide and noncannabinoid ethanolamides, but there was no evidence that these effects were influenced by the coadministration of CBD. It is possible that such effects may be evident with higher doses of CBD or after chronic administration. The progressive reduction in pretreatment anandamide and DEA levels across sessions may be related to repeated exposure to THC or participants becoming less anxious about the testing procedure and requires further investigation. The
study was registered on clinicaltrials.gov (NCT05170217).