Slikker W, Paule M G, Ali S F, Scallet A C, Bailey J R
Pharmacodynamics Branch, National Center for Toxicological Research, Jefferson, Arkansas 72079-9502.
Fundam Appl Toxicol. 1991 Aug;17(2):321-34. doi: 10.1016/0272-0590(91)90222-p.
This report is the first in a series about a large multidisciplinary study designed to determine whether chronic marijuana (MJ) smoke exposure results in residual behavioral and/or neuropathological alterations in the rhesus monkey. Prior to the initiation of a year of chronic MJ smoke exposure, 64 periadolescent male rhesus monkeys were trained for 1 year to perform five operant behavioral tasks and then divided, according to their performance in these tasks, into four exposure groups (n = 15-16/group): (1) a high dose (HI) group, exposed 7 days/week to the smoke of one standard MJ cigarette; (2) a low dose (LO) group, exposed on weekend days only to the smoke of a standard MJ cigarette; (3) an extracted MJ cigarette (EX) group, exposed 7 days/week to the smoke of one ethanol-extracted MJ cigarette; and (4) a sham group (SH), exposed 7 days/week to sham exposure conditions. Daily exposures for 1 year were accomplished using a mask that covered the subjects' nose and mouth. Average body weights (initially 3.7 +/- 0.5 kg, mean +/- SD) and rates of weight gain (approximately 0.1 kg/month) were the same for all groups throughout the entire experiment. During the first week of exposure, plasma concentrations of delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-THC in the HI group were 59 +/- 7 (mean +/- SE) and 5.5 +/- 1.5 ng/ml, respectively, 45 min after MJ smoke administration and did not change significantly at similar times after exposure throughout the remainder of the year. Whole blood carboxyhemoglobin levels increased to approximately 13% 1 min after exposure to smoke in either the MJ or the EX groups. Comparison of blood chemistry and hematology values before, during, and after exposure indicated no differences for most parameters. During exposure, lymphocytes, alkaline phosphatase and gamma-glutamyl transferase were depressed in the HI group compared to in the SH group. During exposure, aspartate aminotransferase was elevated for both the HI and EX groups, suggesting a general effect of smoke exposure. Because these effects were transient and remained within the range of reported normal values, these data indicate that long-term, experimental exposure to MJ smoke is feasible and does not compromise the general health of the rhesus monkey.
本报告是关于一项大型多学科研究系列中的第一篇,该研究旨在确定长期接触大麻(MJ)烟雾是否会导致恒河猴出现残留的行为和/或神经病理学改变。在开始为期一年的长期MJ烟雾暴露之前,64只青春期雄性恒河猴接受了1年的训练,以执行五项操作性行为任务,然后根据它们在这些任务中的表现分为四个暴露组(每组n = 15 - 16):(1)高剂量(HI)组,每周7天暴露于一支标准MJ香烟的烟雾中;(2)低剂量(LO)组,仅在周末暴露于标准MJ香烟的烟雾中;(3)提取的MJ香烟(EX)组,每周7天暴露于一支乙醇提取的MJ香烟的烟雾中;(4)假手术组(SH),每周7天暴露于假暴露条件下。使用覆盖受试者口鼻的面罩进行为期1年的每日暴露。在整个实验过程中,所有组的平均体重(初始体重为3.7 +/- 0.5 kg,平均值 +/- 标准差)和体重增加率(约0.1 kg/月)相同。在暴露的第一周,HI组在吸入MJ烟雾后45分钟时,血浆中Δ-9-四氢大麻酚和11-去甲-9-羧基-THC的浓度分别为59 +/- 7(平均值 +/- 标准误)和5.5 +/- 1.5 ng/ml,并且在该年剩余时间的类似暴露时间后没有显著变化。在MJ组或EX组中,暴露于烟雾后1分钟时,全血碳氧血红蛋白水平升高至约13%。暴露前、暴露期间和暴露后的血液化学和血液学值比较表明,大多数参数没有差异。在暴露期间,与SH组相比,HI组的淋巴细胞、碱性磷酸酶和γ-谷氨酰转移酶降低。在暴露期间,HI组和EX组的天冬氨酸转氨酶均升高,表明烟雾暴露具有普遍影响。由于这些影响是短暂的,并且仍在报告的正常范围内,这些数据表明长期实验性暴露于MJ烟雾是可行的,并且不会损害恒河猴的总体健康。