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Biomedical subjects

R R Griffiths

Publications and source records attributed to R R Griffiths.

At least 163 records · Page 9Linked to original sources
PubMed1984

Determinants of puff duration in cigarette smokers: I.

This research was undertaken to provide information about variables offt might account for the decreases in puff duration that consistently occur as a whole cigarette is smoked. Cigarette smoking was investigated under conditions in which subjects smoked cigarettes which they could not see. In a series of three experiments, the length of the tobacco rod, the length of the cigarette holder, and the cigarette nicotine delivery were systematically manipulated. The results showed that puff duration correlates with the length of the tobacco rod, and that visual stimulus control, satiation, distance from the burning ember to the smoker's mouth, nicotine delivery, particulate build-up during smoking, and subjective acceptability of cigarette smoke do not contribute significantly to the control of puff duration.

Adult↗
PubMed1984

Precipitated and spontaneous withdrawal in baboons after chronic dosing with lorazepam and CGS 9896.

In order to assess the ability of lorazepam (20 mg/kg/day) and CGS 9896 (100 mg/kg/day) to produce physical-dependence in baboons, the occurrence of Ro 15-1788 precipitated withdrawal signs and spontaneous withdrawal signs were determined. Lorazepam-treated baboons displayed precipitated withdrawal signs following the administration of Ro 15-1788 (5 mg/kg), and displayed mild to moderate spontaneous withdrawal signs following termination of drug treatment. CGS 9896-treated baboons did not display Ro 15-1788 precipitated withdrawal signs and displayed either no or only mild spontaneous withdrawal signs.

Animals↗
PubMed1984

Determinants of puff duration in cigarette smokers: II.

Studies were conducted to provide information about variables that might account for decreases in puff duration that consistently occur as a whole cigarette is smoked. In two experiments, cigarette smoking was investigated under conditions in which subjects smoked cigarettes which they could not see. Puff duration was shown to covary with manipulations of resistance to draw--increasing tobacco rod length or adding filters proximal or distal to the smoke stream increased puff duration. Filtration of the smoke stream did not influence puff duration when resistance to draw was controlled. Comparison of changes in smoke temperature with changes in puff duration across a whole cigarette, and manipulation of smoke temperature by use of different length cigarette holders suggested that temperature did not appreciably control puff duration. A final experiment with nonhuman stimulated puffing of constant puff volume showed that both tobacco rod length and cigarette brand affected puff duration and suggests the possibility that the physics of smoke passing through the cigarette may be fundamental determinant of changes in puff duration during human smoking.

Adult↗
PubMed1984

Diazepam and methadone interactions in methadone maintenance.

Survey study data and high rates of diazepam use/abuse in methadone maintenance suggest that acute administration of diazepam with daily methadone doses may enhance methadone effects. Acute subjective and physiologic effects of single oral doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150%, and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose) were assessed under double-blind conditions. The subjects were five adult male patients on methadone maintenance with histories of diazepam abuse who were receiving 50 to 60 mg methadone a day. Physiologic measures were continuously monitored for 30 min before and for 2 hr after dosing. Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90, and 120 min after dosing. Methadone induced dose-dependent increases in pupil constriction and scores on a subjective opioid effects rating scale, but diazepam had no significant effect on either. The combination of methadone at 150% of the maintenance dose with 40 mg diazepam induced increases in these measures greater than those induced by either drug dose alone. Drug combinations, however, were more frequently identified as being benzodiazepine/barbiturate-like than as methadone-like. Thus although the subjective effects of the drug combination are distinguishable from those of methadone alone, diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioid effects that may be related to the relatively great use/abuse of diazepam in this population.

Administration, Oral↗
PubMed1984

Comparison of diazepam and oxazepam: preference, liking and extent of abuse.

In a residential hospital research ward setting, the effects of and preference for placebo, oxazepam (480 mg) and diazepam (40, 80 and 160 mg) were studied in human volunteers with histories of sedative drug abuse. Doses p.o. were administered every 3rd day under double-blind conditions. After an initial exposure to the letter-coded test drugs, a series of choice days was scheduled on which subjects chose between two available drug alternatives. Compared with oxazepam, diazepam produced greater liking (area under the time-action curve), peak liking and euphoria and was judged to be of greater monetary street value. Diazepam was categorized as producing barbiturate-like subjective effects more frequently than was oxazepam (54 vs. 21%), whereas oxazepam was identified as placebo more often than diazepam (32 vs. 4%). Diazepam was associated with a more rapid onset of effect than was oxazepam, and this rapid onset was repeatedly cited by subjects in poststudy written comments as being a desirable feature of the drug effect. In choice tests, 80 and 160 mg of diazepam were preferred to 480 mg of oxazepam on 62.5 and 91.7% of the choice tests, respectively. In choice tests between placebo and drug, placebo was never preferred to diazepam; however, placebo was preferred to oxazepam on 21.4% of choice tests. Overall, these results extend previous experimental observations suggesting that diazepam has a higher abuse liability than oxazepam. The results are also compatible with an analysis of epidemiological data showing that diazepam abuse uniformly exceeds oxazepam abuse on seven epidemiological measures of drug abuse.

Adult↗
PubMed1984

Effects of methadone on human cigarette smoking and subjective ratings.

In order to study possible interactions between opioids and cigarette smoking, we examined the effects of oral methadone administration on the smoking behavior of five male methadone-maintenance patients. Isolated subjects smoked their regular brand of cigarettes ad libitum in a naturalistic laboratory environment while reading or watching television. Ninety minutes before each daily 2-hr smoking session subjects received either placebo, dextromethorphan (a taste blind) or one of three doses of methadone, 0.5, 1.0 or 2.0 times their regular maintenance dose (40-60 mg). Each subject received each treatment five times, in a mixed order across days. Methadone pretreatment resulted in a dose-related increase in the number of cigarettes smoked per session (from a mean of 2.8 after placebo to 5.6 after the high dose of methadone). The total time spent puffing during the session increased from a mean of 27 sec after placebo to 74 sec after the high dose of methadone. CO levels in expired air (a measure of actual smoke inhalation) showed corresponding dose-related increases. Methadone administration also resulted in dose-related decreases in pupil diameter and increases in subjective ratings of smoking satisfaction and dose-strength. Dextromethorphan had no significant effects on any measure of smoking behavior or subjective response. The results demonstrate that methadone can produce substantial increases in cigarette smoking and may have implications regarding the proposed role of endogenous opioids in the smoking process.

Dextromethorphan↗
PubMed1983

Differential effects of diazepam and pentobarbital on mood and behavior.

The effects of administering moderately high doses of diazepam and pentobarbital sodium for five consecutive days to subjects with histories of sedative drug abuse were examined. The two drugs produced similar dose-related effects on psychomotor performance, daytime sleeping, and ratings of magnitude of drug effects. Diazepam, but not pentobarbital, produced dose-related decreases in staff ratings of subjects' mood and social interactions and increases in staff ratings of subjects' hostility, complaining, and unusual behavior. During the placebo washout periods that followed drug administration. diazepam, but not pentobarbital, was associated with carry-over effects. The diazepam-produced deterioration in mood and social behavior was a subtle effect observed in a population for which usual therapeutic indications were lacking and at higher than usual therapeutic doses. The syndrome may, however, occur with long-term diazepam use or misuse in therapeutic settings and, hence, warrants clinical awareness in monitoring the course of treatment.

Adolescent↗
PubMed1983

Oral self-administration of methohexital in baboons.

Oral self-administration of methohexital was generated in baboons that were food-restricted but not water-deprived. Stable intake of an 8% ethanol solution (two baboons) or water (two baboons) was first established in 3-h-sessions. Increasing concentrations of methohexital (0.005-10 mg/ml) then were substituted with a return to the ethanol or water baseline condition between methohexital conditions. For one baboon in the ethanol baseline condition, drinking was initially suppressed by methohexital substitution, but increased under a food-induced drinking procedure. For all baboons, an inverted U-shaped function generally described the relation between methohexital concentration and volume consumed. Anesthetization was observed at concentrations of 1.6 mg/ml and above. In two-bottle choice tests, three baboons generally drank greater volumes of methohexital than water at concentrations of 0.8 mg/ml and above. After a methohexital-free period of 1-3 months methohexital self-administration was readily reestablished.

Animals↗
PubMed1983

Human progressive-ratio performance: maintenance by pentobarbital.

Within a residential research ward, five human volunteers with histories of sedative drug abuse were exposed to progressive-ratio schedules of pentobarbital (200, 400, 600 mg) or placebo self-administration. All doses were letter-coded and administered under double-blind conditions. To obtain a single letter-coded dose, three subjects were required to press a set of buttons a specified number of times and two subjects were required to ride a stationary bicycle for a specified period of time. Only one dose could be obtained per day and the button-pressing or riding requirement for each letter-coded dose was increased over successive sessions until subjects failed to meet the progressive-ratio requirement (i.e., the subject chose not to work for the dose). Drug-effect ratings and subjective measures were taken 2 h after drug administration. Pentobarbital maintained dose-related increases in the maximum progressive-ratio requirement completed, the subject and staff ratings of drug effect, the subject ratings of drug 'liking', and the scores on the PCAG scale of the Addiction Research Center Inventory. The present study suggests that progressive-ratio schedules are sensitive and valid procedures for providing information about the relative reinforcing efficacy of drugs.

Adult↗
PubMed1983

Nicotine self-administration in baboons.

Two experiments were conducted in which responding maintained by nicotine and cocaine was studied under two different schedules of drug delivery. In Experiment 1, nicotine (0.01-0.32 mg/kg IV) was available under a fixed-ratio 2 timeout 15 sec reinforcement schedule. When nicotine was substituted for cocaine or saline, dose-dependent differences in self-administration were evident across the first five sessions, resulting in an inverted U-shaped dose-effect curve. With continued exposure to each nicotine dose, however, number of injections generally stabilized at levels not very different, if at all, from saline; and the terminal dose-effect functions generally were low and flat. In Experiment 2, nicotine (0.01-0.56 mg/kg IV) was available under a fixed-interval 5 min timeout 60 sec reinforcement schedule. Response rates were considerably lower and response patterning was less likely to be scalloped than when responding was maintained by either cocaine or food, but number of injections was higher than those maintained by saline. When fixed-interval value was varied, number of nicotine reinforcements remained low and virtually constant, but number of food reinforcements increased as the fixed interval decreased. The present results, along with those from previous studies, suggest that the ability of nicotine to serve as a reinforcer appears to be strongly influenced by the conditions of drug availability, perhaps more so than for other drugs of abuse.

Animals↗
PubMed1983

Cigarette smoking and subjective response in alcoholics: effects of pentobarbital.

The effects of oral pentobarbital on cigarette smoking and subjective response were determined in five adult men with histories of alcoholism and cigarette-smoking habits. Subjects resided in a residential research unit for the 6-wk study and were individually tested 5 days a wk in rooms that were equipped for automatic monitoring of cigarette-smoking behavior. Each subject was tested with placebo, one dose level of ethanol (either 89 or 134 gm absolute ethanol), and each of three pentobarbital doses (200 to 900 mg), in at least four randomized block sequences. Ethanol induced increases in puffs and other smoking measures in all subjects. Pentobarbital increased smoking in two subjects, whereas it did not induce change or suppress smoking in the other subjects. Both pentobarbital and ethanol increased scores on scales of the Addiction Research Center Inventory and other self-report measures. The results indicate that the effects of pentobarbital on smoking differ from those of ethanol, and that the effects of both drugs on smoking may depend on previous experience of the subject in the use of those drugs.

Adult↗
PubMed1983

Effects of caffeine on cigarette smoking and subjective response.

We examined the effects of oral caffeine on cigarette smoking and subjective response in a group of six smokers who smoked cigarettes ad libitum in a naturalistic laboratory environment. A within-subject, repeated-measures design was used, and each subject received placebo, caffeine base (50 to 800 mg), or d-amphetamine sulfate (25 mg) on several occasions before 90-min daily smoking sessions. There was no evidence of an increase in the number of cigarettes smoked or the amount of smoke inhaled per session after caffeine. Caffeine increased salivary caffeine concentrations, arm tremor, and self-reported measures of mood and subjective response. The major subjective effects of caffeine were increases in tension-anxiety and dysphoric-somatic effects. In contrast, d-amphetamine induced increases in the number of cigarettes smoked and in the amount of smoke inhaled per session. The major subjective effects of 25 mg of d-amphetamine were increases in measures of well-being, euphoria, and mental efficiency. Results demonstrate that caffeine and d-amphetamine have different effects on cigarette-smoking behavior as well as on subjective response and suggest that the positive correlation between cigarette smoking and coffee drinking is not the result of a simple pharmacologic effect of caffeine.

Adolescent↗