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Biomedical subjects

S T Higgins

Publications and source records attributed to S T Higgins.

At least 73 records · Page 4Linked to original sources
PubMed1993

Abuse liability of alprazolam relative to other commonly used benzodiazepines: a review.

Nonhuman and human studies comparing the abuse liability of alprazolam to other commonly used benzodiazepines are reviewed. These studies are reviewed to determine to what extent prospective, controlled, experimental studies support opinions that alprazolam's abuse liability is greater than that of other commonly used benzodiazepines. Studies comparing the self-administration of alprazolam, the discriminative stimulus effects of alprazolam, self-reported effects of alprazolam, physiological dependence on alprazolam, and adverse effects of alprazolam relative to other benzodiazepines are reviewed. Overall, the experimental literature does not support the widely held belief that alprazolam's abuse liability is greater than that of other benzodiazepines, but much more research is needed. Such research should focus explicitly on alprazolam's reinforcing effects, and the nature and severity of the discontinuation syndrome associated with its long-term use. Important issues such as selection of an appropriate comparison drug, selection of an appropriate population, dosing regimen and test doses need to be considered in future studies.

Alprazolam↗
PubMed1993

Achieving cocaine abstinence with a behavioral approach.

OBJECTIVE: The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals. METHOD: The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens. RESULTS: Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group. CONCLUSIONS: This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence.

Ambulatory Care↗
PubMed1993

The taking of free condoms in a drug abuse treatment clinic: the effects of location and posters.

Drug abuse treatment programs can help reduce high-risk sexual behavior in drug users by promoting condom use. This study examined the influence of distribution location and poster prompts on the taking of free condoms in a drug abuse treatment clinic. Over 6 months, condoms were available alternately, with and without poster prompts, in the clinic's private restroom or public waiting area. Overall, 381% more condoms were taken from the restroom. The presence of poster prompts did not affect condom taking. These results suggest that distribution location is a critical factor in promoting condom taking in public clinic.

Advertising↗
PubMed1993

A novel-response procedure enhances the selectivity and sensitivity of a triazolam discrimination in humans.

Placebo-appropriate responding in drug discrimination can be difficult to interpret because such responding can indicate either the absence of any drug effect or the absence of a specific drug effect. This study addressed the overinclusiveness of placebo-appropriate responding by providing a response alternative for novel-drug effects (i.e., effects unlike the training stimuli). This "novel-response procedure" used instructions that indicated that only responses on a novel-appropriate manipulandum would be reinforced in the presence of novel drug effects. Four healthy male volunteers (ages 19-32) were trained to discriminate 0.32 mg/70 kg of triazolam from placebo. Then, dose-effect curves were determined for triazolam (0.1-0.32 mg/70 kg) and d-amphetamine (5 and 20 mg/70 kg) with a standard two-response procedure (drug vs. placebo) and the novel-response procedure. Triazolam produced dose-related increases in triazolam-appropriate responding with both procedures. d-Amphetamine produced predominantly placebo-appropriate responding with the two-response procedure and predominantly novel-appropriate responding with the novel-response procedure. Unexpectedly, the triazolam dose-effect curve obtained with the novel-response procedure was shifted to the left relative to the two-response procedure for discrimination measures. A similar effect was evident for both the triazolam and d-amphetamine dose-effect curves for some self-report measures. Because of the increased selectivity of placebo-appropriate responding and the increased potency of the drug stimulus, the novel-response procedure may represent a methodological advance for drug discrimination research.

Adolescent↗
PubMed1993

Acute effects of triazolam and lorazepam on human learning, performance and subject ratings.

Triazolam (0,0.125, 0.25, 0.5, and 0.75 mg/70 kg) and lorazepam (0, 1, 2, 4 and 6 mg/70 kg) were compared in eight healthy men by using a double-blind, crossover design. Triazolam was chosen for study to examine experimentally whether it produces greater behavioral impairment than other benzodiazepines as reported previously. Lorazepam was chosen as the comparison drug because of its well documented behavioral effects and because it has a short metabolic half-life and no active metabolite, which eliminates the possible confounding effects of drug accumulation. Drug effects were assessed before and every 30 min for 8 hr after drug administration. Learning was chosen for study because it is a fundamental component of more complex behavioral processes such as recall, and benzodiazepines are known to disrupt learning. A psychomotor task and subject-rating scales, assessing drug effects and abuse potential, were also included to provide a more comprehensive comparison of these compounds. Triazolam and lorazepam dose-dependently disrupted learning and psychomotor performance and increased subject ratings of sedation to a comparable degree. These findings do not support allegations that triazolam produces greater behavioral impairment than other commonly used benzodiazepines.

Adult↗
PubMed1992

Behavioral economics of drug self-administration. IV. The effects of response requirement on the consumption of and interaction between concurrently available coffee and cigarettes.

In behavioral economics, consumption of a reinforcer is determined by its price and by the price of other available reinforcers. This study examined the effects of price manipulations on the consumption of concurrently available coffee and cigarettes. During fifteen 4-h sessions, coffee and cigarettes were concurrently available according to fixed-ratio (FR) schedules of reinforcement. After consumption stabilized under a fixed ratio 100 for both reinforcers, the response requirement for each reinforcer was varied separately (i.e., FR 100, 1000 and 2500), while the response requirement for the other reinforcer was kept at 100. Increasing the FR value decreased coffee and cigarette consumption to a similar degree. Also, as the price for cigarettes increased (and consumption decreased), coffee consumption decreased; however, as the price of coffee increased, cigarette consumption did not change. These results indicate that for this setting the reinforcing effects of cigarettes and coffee were comparable but interacted asymmetrically. These findings when analyzed and quantified via economic concepts of own-price and cross-price elasticity illustrate the viability of using behavioral economics to examine drug self-administration in a choice paradigm.

Adolescent↗
PubMed1992

Behavioral economics of drug self-administration. III. A reanalysis of the nicotine regulation hypothesis.

The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unit-price analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential health risks for smokers who are unable to stop smoking.

Behavior↗
PubMed1992

Forced-choice versus free-choice procedures: caffeine self-administration in humans.

Methodological comparisons of procedures for drug self-administration are rare. In studies examining the reinforcing effect of caffeine in humans, caffeine self-administration usually has been inferred from performance under forced-choice procedures. In the present experiment, caffeine self-administration via coffee was compared under forced-choice and free-choice conditions; i.e., when subjects were and were not required to use a minimum number of coffees. Ten moderate coffee drinkers (2-7 cups/day) were assigned to forced- and free-choice conditions using a randomized cross-over design. Under each choice condition, subjects completed six independent, double-blind trials, consisting of a 2-day exposure period followed by a 2-day test period. During exposure, subjects consumed either decaffeinated or caffeinated (100 mg/serving) coffee on day 1 and the other coffee on day 2. During the test period, subjects had concurrent access to the same decaffeinated and caffeinated coffees. Under the forced-choice condition, subjects were required to drink at least four cups of coffee per day during the test period. Under the free-choice condition, subjects did not have a minimum-cup requirement. In general, the relative rate at which subjects self-administered caffeinated versus decaffeinated coffee was similar across choice conditions, even though subjects self-administered significantly fewer cups of both coffee types under the free-choice than the forced-choice condition. These results suggest that, at least for caffeine, forced-choice and free-choice procedures produce comparable results. Whether this finding generalizes to a context in which caffeine or another drug is more robustly self-administered, remains to be determined.

Adult↗
PubMed1992

Triazolam as a discriminative stimulus in humans.

Seven healthy normal male and female volunteers (19-42 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg; e.g. drug A) and placebo (e.g. drug B). During the first four daily sessions, drug A and drug B were administered orally in capsules 60 min prior to the session on alternate days and subjects were informed of the drug label at the time of drug administration. Subsequently, drug A and drug B were administered in a randomized-block fashion and subjects identified the drug code they thought they received. Subjects were informed of the drug code post-session. Once the criterion for discrimination was met (i.e. correct drug code identification on four consecutive sessions), the dose-effect curve for triazolam (0.1-0.75 mg/70 kg) was determined. The discrimination was acquired in all subjects; triazolam (0.32 mg/70 kg) and placebo produced approximately 85-95% correct responding. During the dose-effect curve determination, triazolam produced dose-related increases in triazolam-appropriate responding and self-reported sedation and drug strength. These results indicate that a triazolam-placebo discrimination can be acquired and that the triazolam discriminative stimulus effect is related to dose and to self-reported sedation.

Adult↗
PubMed1992

The scientific/clinical response to the cocaine epidemic: a MEDLINE search of the literature.

Index Medicus (1966-1990) was searched to quantify and characterize the scientific/clinical community's responses to the cocaine epidemic. The rate of growth in the cocaine literature was compared with the rate of growth in the heroin and marijuana literatures in the 1960s and 1970s. Articles on cocaine increased dramatically over the past 7 years suggesting a clear response from the scientific/clinical community to the public health problems presented by the cocaine epidemic. That literature spans a wide range of areas addressing many scientific and health-care issues. This increase in cocaine citations is similar to that which occurred previously in response to use of heroin and marijuana.

Cocaine↗
PubMed1992

Supersensitivity to naloxone following acute morphine pretreatment in humans: behavioral, hormonal and physiological effects.

The effects of naloxone (10 mg/70 kg) given 6 h following acute exposure to morphine (4, 8, 16 mg/70 kg) were assessed in 5 opiate-abusing volunteers who were not physically dependent upon entering the study. Naloxone increased cortisol plasma levels more following morphine than placebo pretreatment. Naloxone reversed the effects of morphine on pupil diameter and oral temperature and decreased skin temperature as a function of morphine pretreatment. Subjects' ability to detect the effects of naloxone, their scores on an opiate-withdrawal questionnaire, and their visual-analog ratings of 'bad effects', 'chills', 'confused' and 'restlessness' increased when naloxone followed pretreatment with 8 and 16 mg, but not 4 mg, of morphine. Performance on the Digit Symbol Substitution Test was not discernibly affected under any of the dose conditions. Overall, results from the present study provide further evidence in humans that the administration of naloxone shortly following acute morphine pretreatment increases naloxone sensitivity, produces signs and symptoms typical of opiate withdrawal and that these effects are dependent on the dose of morphine administered.

Adult↗
PubMed1992

Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?

OBJECTIVE: The authors reviewed basic science and clinical data on caffeine abuse, dependence, and withdrawal in order to make a conclusion about whether these disorders exist and should be included in DSM-IV and ICD-10. METHOD: Studies were located through computerized searches, reference sections of published articles, and written requests. RESULTS: The studies show that abstinence from caffeine induces a withdrawal syndrome of headache, fatigue, and drowsiness which begins within 12-24 hours and lasts about 1 week. The syndrome can be severe and appears to be one reason for continued use of coffee. The prevalence of this caffeine withdrawal syndrome is unknown. Use of caffeine may aggravate some common behavioral and medical disorders. In double-blind tests, a subset of coffee and soda drinkers reliably self-administered caffeinated beverages in preference to uncaffeinated beverages. Clinical indicators of dependence, such as difficulty stopping use of caffeine and use despite harm, have not been documented. CONCLUSIONS: Caffeine withdrawal but not caffeine abuse or dependence should be included as a diagnosis in DSM-IV and ICD-10. Future research should focus on whether some caffeine users exhibit clinical indicators of drug dependence.

Caffeine↗
PubMed1992

Effects of cocaine and alcohol, alone and in combination, on human learning and performance.

The acute effects of cocaine hydrochloride (4 to 96 mg/70 kg) and alcohol (0 to 1.0 g/kg), administered alone and in combination, were assessed in two experiments with human volunteers responding under a multiple schedule of repeated acquisition and performance of response chains. Subjects were intermittent users of cocaine and regular drinkers who were not cocaine or alcohol dependent. Alcohol was mixed with orange juice and ingested in six drinks within 30 min; cocaine was administered intranasally 45 min after completion of drinking. In each component of the multiple schedule, subjects completed response sequences using three keys of a numeric keypad. In the acquisition component, a new sequence was learned each session. In the performance component, the response sequence always remained the same. Results were consistent in both experiments, despite variations in the order in which the drugs were tested alone and in combination. Alcohol administered alone increased overall percentage of errors and decreased rates of responding in the acquisition component, whereas responding in the performance component generally was unaffected. Cocaine administered alone decreased rates of responding but did not affect accuracy of responding in the acquisition component, and enhanced accuracy of responding without affecting rates of responding in the performance component. The combined doses of cocaine and alcohol attenuated the effects observed with alcohol and cocaine alone. These results suggest that, under the conditions investigated in this study, (a) alcohol produces greater behavioral disruption than cocaine or cocaine-alcohol combinations, (b) cocaine and alcohol each attenuate effects of the other, and (c) such attenuation is most pronounced for cocaine attenuating the disruptive effects of alcohol.

Adult↗
PubMed1992

Emergent equivalence relations between interoceptive (drug) and exteroceptive (visual) stimuli.

Conditional "if-then" relations between drug (interoceptive) stimuli and visual (exteroceptive) stimuli were taught to 4 normal humans. Interoceptive stimuli were the effects produced by 0.32 mg/70 kg triazolam (a prototypical benzodiazepine) and placebo (lactose-filled capsules); exteroceptive stimuli were black symbols on white flash cards. Following the training of the prerequisite conditional relations, tests of emergent relations were conducted between exteroceptive stimuli and between interoceptive and exteroceptive stimuli. Equivalence relations emerged immediately without explicit training for all 4 subjects. Accuracy of responding during the interoceptive-exteroceptive equivalence tests and subjects' self-reports showed consistent discrimination between the drug effects of triazolam and placebo. Finally, a generalization test assessed whether a novel visual stimulus presented in the context of the placebo (i.e., no drug) would generalize to visual stimuli belonging to the placebo stimulus class. All 3 subjects who completed this test reliably chose the visual stimuli belonging to the placebo class and not the visual stimuli belonging to the triazolam stimulus class. The development of equivalence relations between interoceptive and exteroceptive stimuli demonstrates that private and public stimulus events can emerge as members of the same equivalence class. Theoretical and clinical implications are discussed.

Adult↗