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Biomedical subjects

H Kalant

Publications and source records attributed to H Kalant.

243 records · Page 14Linked to original sources

Effect of treatment dose and test system on the development of ethanol tolerance and physical dependence.

The development of ethanol tolerance as a function of daily treatment dosage was examined on two different test systems. Tolerance to the motor-impairment effect of ethanol, as measured by the tilting-plane test, failed to develop after daily administration of 1-3 g/kg, but developed to equal degrees after 4 or 5 g/kg daily. On the other hand, daily treatment with 2, 4 or 6 g/kg all produced significant tolerance to the hypothermic effect, and the extent of tolerance was proportional to the treatment dosage. Twenty-four hours after the termination of ethanol treatment, there was a significant hypothermia in the group treated with 6 g/kg, and at 32 hr hyperthermia occurred in both the 4 and 6 g/kg groups. These results indicate that treatment dosage is an important determinant of the extent of ethanol tolerance and physical dependence, but that the relationship is complex and varies with the test system used.

Alcoholism↗

Differential response to ethanol, pentobarbital and morphine in mice selectively bred for ethanol sensitivity.

Males of two lines of mice, long sleep (LS) and short sleep (SS), that had been selectively bred for their differential sensitivity to ethanol-induced sleep, were examined for their responses to the hypothermic and analgesic effects of ethanol, pentobarbital and morphine, and to the cataleptic effect of morphine. SS mice were found to be less sensitive than the LS animals to ethanol but not pentobarbital-induced analgesia and hypothermia. The SS animals were also less sensitive to morphine-induced hypothermia, but were, by contrast, more sensitive than their LS counterparts to morphine-induced analgesia, while no line differences existed with respect to catalepsy. The rate of morphine disappearance from the blood was somewhat higher in the LS animals but this difference is probably too small to account for the observed differential responses to morphine.

Analgesics↗

Comparison of sensitivity and alcohol consumption in four outbred strains of rats.

Differences in alcohol consumption and in sensitivity to the effects of ethanol were investigated in four outbred rat strains: Fischer 344, Long-Evans, Sprague-Dawley and Wistar. Alcohol consumption was measured in all four strains in three separate subgroups for each strain, using three different concentrations of ethanol (5, 10 and 20% v/v). An intermittent forced alternate-day ethanol presentation procedure (ethanol as the sole fluid for one day followed by only water the next day), as well as a two-bottle choice paradigm, were employed for this purpose. Ethanol-induced hypothermia and motor impairment (tilting plane test) were used to assess sensitivity. Significant differences in alcohol consumption were found among these strains. The Long-Evans strain consumed the highest and Fischer 344 the lowest amount of ethanol. Wistar and Sprague-Dawley were intermediate. However, the strains did not differ in sensitivity to ethanol. Similarly, determination of sensitivity to ethanol on day 0 in separate groups of these four strains (same age and weight, and obtained at the same time from the same supplier) did not reveal graded differences in sensitivity (hypothermia and motor impairment) corresponding to differences in alcohol consumption. These results suggest that sensitivity does not correlate with alcohol consumption.

Analysis of Variance↗

Effect of lipid solubility on the development of chronic cross-tolerance between ethanol and different alcohols and barbiturates.

Tolerance to ethanol and cross-tolerance to other alcohols (n-propanol, n-butanol, t-butanol, isobutanol, t-amyl alcohol, n-amyl alcohol, and benzyl alcohol) and barbiturates (pentobarbital, secobarbital, amobarbital, thiopental, barbital and phenobarbital) that differ in lipid:water partition coefficient was examined in rats after chronic pretreatment with ethanol. Tolerance and cross-tolerance were studied with three different measures (hypothermia, tilt-plane, and rotarod). Tolerance to ethanol resulted in significant cross-tolerance to alcohols with low lipid solubility (n-propanol and t-butanol), whereas no cross-tolerance was seen with alcohols of high lipid solubility (isobutanol, n-amyl alcohol, t-amyl alcohol and benzyl alcohol). Cross-tolerance to n-butanol (which has intermediate lipid solubility) appeared to be metabolic rather than functional. Tolerance to ethanol also resulted in significant cross-tolerance to barbital and phenobarbital, but not to pentobarbital, secobarbital, amobarbital or thiopental. These studies suggest that lipid solubility is an important factor in relation to specificity of cross-tolerance to alcohols and barbiturates.

Alcohols↗

Evaluating the impact of hemp food consumption on workplace drug tests.

Foods containing seeds or oil of the hemp plant (Cannabis sativa L.) are increasingly found in retail stores in the U.S. The presence of delta9-tetrahydrocannabinol (THC) in these foods has raised concern over their impact on the results of workplace drug tests for marijuana. Previous studies have shown that eating hemp foods can cause screening and confirmed positive results in urine specimens. This study evaluated the impact of extended daily ingestion of THC via hemp oil on urine levels of its metabolite 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) for four distinct daily THC doses. Doses were representative of THC levels now commonly found in hemp seed products and a range of conceivable daily consumption rates. Fifteen THC-naïve adults ingested, over four successive 10-day periods, single daily THC doses ranging from 0.09 to 0.6 mg. Subjects self-administered THC in 15-mL aliquots (20 mL for the 0.6-mg dose) of four different blends of hemp and canola oils. Urine specimens were collected prior to the first ingestion of oil, on days 9 and 10 of each of the four study periods, and 1 and 3 days after the last ingestion. All specimens were screened for cannabinoids by radioimmunoassay (Immunalysis Direct RIA Kit), confirmed for THC-COOH by gas chromatography-mass spectrometry (GC-MS), and analyzed for creatinine to identify dilute specimens. None of the subjects who ingested daily doses of 0.45 mg of THC screened positive at the 50-ng/mL cutoff. At a daily THC dose of 0.6 mg, one specimen screened positive. The highest THC-COOH level found by GC-MS in any of the specimens was 5.2 ng/mL, well below the 15-ng/mL confirmation cutoff used in federal drug testing programs. A THC intake of 0.6 mg/day is equivalent to the consumption of approximately 125 mL of hemp oil containing 5 microg/g of THC or 300 g of hulled seeds at 2 microg/g. These THC concentrations are now typical in Canadian hemp seed products. Based on our findings, these concentrations appear to be sufficiently low to prevent confirmed positives from the extended and extensive consumption of hemp foods.

Adult↗