Chronic marijuana smoke exposure in the rhesus monkey. I. Plasma cannabinoid and blood carboxyhemoglobin concentrations and clinical chemistry parameters.
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.
Pharmacodynamics Branch, National Center for Toxicological Research, Jefferson, Arkansas 72079-9502.
W
W
Slikker
M G
MG
Paule
S F
SF
Ali
A C
AC
Scallet
J R
JR
Bailey
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002186:Cannabinoids / Q000097:blood* / Q000493:pharmacokinetics; D002263:Carboxyhemoglobin / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects; D013759:Dronabinol / Q000031:analogs & derivatives / Q000097:blood; D007958:Leukocyte Count; D008253:Macaca mulatta; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects / Q000378:metabolism*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000097:blood
D002186:Cannabinoids; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol; D002263:Carboxyhemoglobin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase