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J D Roache

Publications and source records attributed to J D Roache.

50 records · Page 3Linked to original sources
PubMed1987

Lorazepam and meprobamate dose effects in humans: behavioral effects and abuse liability.

On a residential research ward, the acute effects of placebo, lorazepam (LZ) (1.5-9.0 mg) and meprobamate (MEP) (600-3600 mg) were examined using a within-subject double-blind Latin Square design in nine male subjects with histories of drug abuse. Drug effects were assessed with objective performance tasks, subject estimates of performance, staff ratings of drug effects and subject ratings of drug effects, sleep, mood, drug liking and monetary street value. Generally, both LZ and MEP produced comparable dose-related effects; LZ had a more rapid onset of action and on several measures showed a more shallow dose-response curve than MEP. With LZ, but not MEP, subjects under-estimated the degree to which their performance was impaired and under-rated drug effects as compared to analogous staff ratings. Both drugs produced sedation-like subject ratings of mood and sleep but generally did not produce tranquilization-like ratings. MEP produced subject ratings of drug liking and monetary street value which were equal to or in some cases greater than those of LZ. Relative potency estimations showed that LZ was 510 to 783 times more potent than MEP in producing performance impairment but was only 370 times more potent than MEP in producing subject ratings of drug liking. Overall, these data indicate that the likelihood of abuse of MEP is at least equal to if not greater than that of LZ although LZ may have a greater likelihood of producing adverse behavioral effects such as a performance impairment and under-estimates of the degree of impairment. These data in conjunction with previous results from this laboratory show that the behavioral effects of benzodiazepines can be differentiated from those of other types of sedative/anxiolytics and that MEP displays characteristics of a barbiturate-like profile of action.

Adult↗
PubMed1986

Effects of benzodiazepines on taste aversions in a two-bottle choice paradigm.

Diazepam (DZ) and chlordiazepoxide (CDP) were tested for their ability to antagonize LiCl-established conditioned taste aversions (CTAs) to saccharin in a two-bottle free-choice paradigm. CTAs to saccharin were established in male Sprague-Dawley rats on a chronic fluid-deprivation schedule by the administration of LiCl (3 mEq/kg, IP) following a forced-choice exposure to a novel saccharin solution (0.1%, w/v). Three days later, rats were provided with a two-bottle choice presentation of saccharin and distilled water. Conditioned rats drank distilled water almost exclusively while unconditioned animals preferred saccharin. Pretreatment with DZ (6, 9, 12 mg/kg, IP) and CDP (12 mg/kg, IP) significantly increased the saccharin intake of conditioned rats indicating an attenuation of the manifestation of the CTA. While these results are consistent with the known disinhibitory effects of benzodiazepines, alternative mechanisms involving polydipsia or interactions with the taste characteristics of saccharin could not be excluded. Both hypertonic saline (16%, w/v NaCl) and Barbital Sodium (100 mg/kg) produced polydipsia without attenuating CTAs suggesting that the two-bottle procedure is capable of distinguishing between polydipsic effects and anti-aversion effects for these drugs.

Animals↗
PubMed1986

Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects.

Four healthy male subjects smoked two marijuana cigarettes or one marijuana cigarette and one placebo cigarette, or two placebo cigarettes on separate days in a random order crossover design. Each marijuana cigarette contained 2.8% delta-9-tetrahydrocannabinol (THC). Plasma hormones and THC were measured before and after each smoking session. Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana. Nonsignificant depressions of prolactin, FSH, testosterone and free testosterone and elevation of GH also occurred. Concurrent measures of subjective effects via subscales of the Addiction Research Center Inventory, Single Dose Questionnaire and a Visual Analog Scale were generally elevated. Significant impairment on a psychomotor performance task paralleled elevations in subjective effects, hormone effects and peak THC determinations. Although all the hormone effects were within normal basal ranges, interactions between these systems, and their effects on behavior cannot be discounted.

Adrenocorticotropic Hormone↗
PubMed1986

Repeated administration of diazepam and triazolam to subjects with histories of drug abuse.

The present study examined the effects of repeated administration of diazepam (DZ) and triazolam (TZ) on psychomotor performance and subject-rated drug liking. Subjects were 11 males (30-41 years) who had documented histories of drug abuse and who resided on a behavioral pharmacology research ward. Six subjects received 80 mg DZ every third day (3 subjects) or every sixth day (3 subjects) for a total of 3-6 dosing occasions and six subjects received TZ (2.0 or 3.0 mg) every second day (4 subjects) or every third day (2 subjects) for a total of 3-5 dosing occasions. The results showed that on the first dose occasion, the two drugs produced generally similar degrees of psychomotor impairment and subject-rated drug liking. Following the first DZ dose, subsequent doses produced less of an effect (i.e. single-dose tolerance). Across at least the first three dose occasions, progressive tolerance development was observed with DZ but no tolerance was observed with TZ. It is hypothesized that pharmacokinetic differences between DZ and TZ may account for the difference in the development of tolerance.

Adult↗
PubMed1985

Relative abuse liability of triazolam: experimental assessment in animals and humans.

The abuse liability of a drug is a positive, interactive function of the reinforcing and adverse effects of the drug. The relative abuse liability of the hypnotic benzodiazepine, triazolam, has been controversial. This paper reviews animal and human studies bearing on its relative abuse liability, including data on pharmacological profile, reinforcing effects, liking, speed of onset, discriminative stimulus effects, subjective effects, physiological dependence, rebound and early morning insomnia, drug produced anxiety, lethality in overdose, psychomotor impairment, interactions with ethanol, anterograde amnesia, impaired awareness of drug effect, and other psychiatric and behavioral disturbances. It is concluded that the abuse liability of triazolam is less than that of the intermediate duration barbiturates such as pentobarbital. Although there are considerable data indicating similarities of triazolam to other benzodiazepines, there is also substantial speculation among clinical investigators and some limited data suggesting that the abuse liability of triazolam is greater than that of a variety of other benzodiazepines, and virtually no credible data or speculation that it is less. Further research will be necessary to clarify definitively the abuse liability of triazolam relative to other benzodiazepines.

Amnesia↗
PubMed1985

Comparison of triazolam and pentobarbital: performance impairment, subjective effects and abuse liability.

On a residential research ward, the acute effects of placebo, 0.5 to 3.0 mg of triazolam (TZ) and 100 to 600 mg of pentobarbital (PTB) were examined using a within-subject, double-blind design in male volunteers with documented histories of drug abuse. Drug effects were examined through the use of subject ratings including measures of drug liking and estimates of street value, staff ratings, objective psychomotor/cognitive performance measures, subject estimates of performance, immediate and delayed recognition memory tasks and subject ratings of nighttime sleep quality. Staff ratings and objective performance measures showed that TZ and PTB produced comparable dose-related impairment; TZ had a more rapid onset and a shorter duration of action than PTB. With these measures, TZ was 159 to 274 times more potent than PTB. With subject-rated measures of drug effect, sleepiness and drunkenness, in contrast, TZ produced smaller effects than PTB or was only 135 to 163 times more potent than PTB. Similarly, with subject ratings of drug liking and estimated street value, TZ produced smaller effects than PTB and was only 91 to 122 times more potent than PTB. Other results showed that TZ produced greater amnestic effects than PTB and subjects under the influence of TZ more consistently underestimated the degree of their impairment. Overall, these results suggest that TZ has a lower liability for abuse (likelihood) than PTB, but a greater liability of abuse (hazard) with regard to performance impairment on certain kinds of tasks.

Adult↗
PubMed1984

Relative abuse liability of diazepam and oxazepam: behavioral and subjective dose effects.

The effects of diazepam (10-160 mg) and oxazepam (30-480 mg) were studied in volunteers with histories of drug abuse. Oral doses were administered every third day under double-blind and counterbalanced conditions. Dose-effects with area under the time-action curve data (AUC) showed diazepam to be 2.6-5.7-times more potent than oxazepam on various psychomotor, cognitive, staff-rated, and subjective measures. Comparison of relative potencies showed diazepam to be relatively more potent in producing 'liking' than in producing psychomotor and cognitive effects. Diazepam produced greater peak effects than oxazepam on a number of staff- and subject-rated measures, including liking. Onset of effect was more rapid and time to maximal effect was shorter (1-2 h versus 4-12 h) with diazepam than oxazepam, while time to offset of effect was similar for the two drugs. Diazepam was categorized as producing barbiturate-like subjective effects (38.3%) more frequently than was oxazepam (13.8%), while oxazepam was identified as placebo more often than diazepam. Repeated administration of 160 mg diazepam and 480 mg oxazepam showed that AUC liking was greater for diazepam than oxazepam and that tolerance to psychomotor and cognitive effects occurred with oxazepam but not diazepam. This study suggests that diazepam may have a higher abuse liability than oxazepam.

Adult↗
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↗
PubMed1983

5-hydroxytryptophan-induced conditioned taste aversion to ethanol in the rat.

This experiment was conducted to determine the efficacy of 5-HTP in producing conditioned taste aversions (CTAs) to ethanol in rats restricted to a one-hour daily access to fluid. Administration of 100 mg/kg of DL-5-HTP immediately following novel exposure to ethanol resulted in an aversion of such magnitude that some rats refused to consume the ethanol solution. Since ethanol was the only fluid available to these rats, they eventually died, presumably of dehydration. By comparison, LiCl administration also produced a CTA to ethanol, but no such persistent rejection was observed. Both 5-HTP and LiCl also produced CTAs when saccharin and tartaric acid solutions were used as novel fluids, but these aversions were short-lived and all rats resumed drinking. The causative factor(s) in the persistent ethanol rejection until death observed in rats treated with 5-HTP remain undetermined but the results have indicated that simple CS-UCS associative learning mechanisms are probably not a primary causative factor.

5-Hydroxytryptophan↗
PubMedDate not supplied

Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial.

CONTEXT: Early-onset alcoholism differs from late-onset alcoholism by its association with greater serotonergic abnormality and antisocial behaviors. Thus, individuals with early-onset alcoholism may be responsive to treatment with a selective serotonergic agent. OBJECTIVE: To test the hypothesis that drinking outcomes associated with early vs late-onset alcoholism are differentially improved by the selective 5-HT(3) (serotonin) antagonist ondansetron. DESIGN: Double-blind, randomized, placebo-controlled clinical trial. SETTINGS: University of Texas Health Science Center in Houston (April 1995-June 1998) and University of Texas Health Science Center in San Antonio (July 1998-December 1999). PARTICIPANTS: A total of 321 patients with diagnosed alcoholism (mean age, 40.6 years; 70.5% male; 78.6% white) were enrolled, 271 of whom proceeded to randomization. INTERVENTIONS: After 1 lead-in week of single-blind placebo, patients were randomly assigned to receive 11 weeks of treatment with ondansetron, 1 microg/kg (n = 67), 4 microg/kg (n = 77), or 16 microg/kg (n = 71) twice per day; or identical placebo (n = 56). All patients also participated in weekly standardized group cognitive behavioral therapy. MAIN OUTCOME MEASURES: Self-reported alcohol consumption (drinks per day, drinks per drinking day, percentage of days abstinent, and total days abstinent per study week); and plasma carbohydrate deficient transferrin (CDT) level, an objective and sensitive marker of transient alcohol consumption. RESULTS: Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 microg/kg twice per day) compared with those who were administered placebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P =.03, P =.01, and P =.02, respectively) and drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P =.03, P =.004, and P =.03, respectively). Ondansetron, 4 microg/kg twice per day, was superior to placebo in increasing percentage of days abstinent (70.10 vs 50.20; P =.02) and total days abstinent per study week (6.74 vs 5.92; P =.03). Among patients with early-onset alcoholism, there was a significant difference in the mean log CDT ratio between those who received ondansetron (1 and 4 microg/kg twice per day) compared with those who received the placebo (-0.17 and -0.19 vs 0.12; P =.03 and P =.01, respectively). CONCLUSION: Our results suggest that ondansetron (particularly the 4 microg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality. JAMA. 2000;284:963-971

Adult↗
PubMedDate not supplied

A role for valproate in the treatment of sedative-hypnotic withdrawal and for relapse prevention.

In the human central nervous system, the gamma-aminobutyric acid (GABA) type A receptor complex undergoes changes with both acute and chronic exposure to sedative-hypnotic drugs. These changes contribute to both the acute effects of these drugs as well as the chronic effects of sedative-hypnotic dependence, withdrawal, and drug craving. Clinically these chronic effects are difficult to treat in patients dependent on ethanol or benzodiazepines. Valproate may return the GABA type A receptor function to a state more closely resembling its normal function. By this mechanism, it is possible to reduce the symptoms of sedative-hypnotic withdrawal and relapse.

Chronic Disease↗