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Biomedical subjects

S T Higgins

Publications and source records attributed to S T Higgins.

At least 19 recordsLinked to original sources
PubMed1995

The behavioral economics of concurrent drug reinforcers: a review and reanalysis of drug self-administration research.

In economics, goods can function as substitutes, complements, or be independent of one another. These concepts refer to increases, decreases, or no change in the consumption of one item as the price of a second item increases. This review examined whether these economic terms can be used to describe relationships between concurrently available reinforcers in drug self-administration research. Sixteen drug self-administration studies that examined the effects of concurrent reinforcers were identified through a MEDLINE search. Across these studies, the following substances were employed: caffeinated coffee, cocaine, etonitazene, ethanol, heroin, food, methadone, morphine, nicotine cigarettes, pentobarbital, phencyclidine, sucrose and water. These studies were reanalyzed and the results were shown to be consistent with these economic notions. These analyses also showed that relationships among the concurrently available reinforcers were reliable within and across studies, that concurrently available reinforcers can affect each other asymmetrically, and that the relative price may determine the magnitude of effect for substitutes. These findings suggest that these economic concepts may be useful in characterizing the type and magnitude of interactions between concurrently available reinforcers and may suggest potential mechanisms that determine these relationships.

Alcohol Drinking↗
PubMed1994

Incentives improve outcome in outpatient behavioral treatment of cocaine dependence.

OBJECTIVE: To assess whether incentives improved treatment outcome in ambulatory cocaine-dependent patients. METHOD: Forty cocaine-dependent adults were randomly assigned to behavioral treatment with or without an added incentive program. The behavioral treatment was based on the Community Reinforcement Approach and was provided to both groups. Subjects in the group with incentives received vouchers exchangeable for retail items contingent on submitting cocaine-free urine specimens during weeks 1 through 12 of treatment, while the group without incentives received no vouchers during that period. The two groups were treated the same during weeks 13 through 24. RESULTS: Seventy-five percent of patients in the group with vouchers completed 24 weeks of treatment vs 40% in the group without vouchers (P = .03). Average durations of continuous cocaine abstinence documented via urinalysis during weeks 1 through 24 of treatment were 11.7 +/- 2.0 weeks in the group with vouchers vs 6.0 +/- 1.5 weeks in the group without vouchers (P = .03). At 24 weeks after treatment entry, the voucher group evidenced significantly greater improvement than the no-voucher group on the Drug scale of the Addiction Severity Index (ASI), and only the voucher group showed significant improvement on the ASI Psychiatric scale. CONCLUSIONS: Incentives delivered contingent on submitting cocaine-free urine specimens significantly improve treatment outcome in ambulatory cocaine-dependent patients.

Adult↗
PubMed1994

Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure.

Seven healthy normal male and female volunteers (21-31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., > 85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), the benzodiazepine diazepam (10-32 mg/70 kg) and the opioid agonist hydromorphone (1-6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of "like novel" and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.

Adult↗
PubMed1994

Influence of an alternative reinforcer on human cocaine self-administration.

Identifying factors that modulate cocaine self-administration is fundamental to the development of effective strategies to treat and prevent cocaine abuse. In the present study, the influence of an alternative reinforcer on the probability of cocaine use was examined in four adult humans under controlled laboratory conditions. During eleven test sessions, subjects chose between cocaine hydrochloride vs. placebo or between cocaine vs. varying amounts of money (0-$2.00/choice). Subjects made a maximum of 10 exclusive choices per session. Cocaine and placebo were administered intranasally in 10 mg unit doses under double-blind conditions. Subjects exclusively chose cocaine over placebo demonstrating that the drug functioned as a reinforcer. During sessions comparing cocaine vs. money, choice of cocaine decreased as the amount of money available in the monetary option increased, with all subjects exclusively choosing the monetary option in the $2.00 per choice condition. These results systematically replicate and extend to humans prior findings in laboratory animals demonstrating that the availability of alternative, nondrug reinforcers can significantly decrease cocaine use.

Administration, Intranasal↗
PubMed1994

Applying behavioral concepts and principles to the treatment of cocaine dependence.

Cocaine dependence continues to be a widespread and serious public health problem in the US. Unfortunately, no consensus exists about how to treat cocaine dependence. Various pharmacological and psychological therapies have been investigated with mixed results. In this report we review findings from several studies conducted to assess the efficacy of an outpatient behavioral treatment for cocaine dependence. The treatment is based on the concepts and principles of behavior analysis and behavioral pharmacology. Results obtained to date indicate the treatment is acceptable to patients, retains them in treatment, engenders clinically significant levels of cocaine abstinence and can be adapted to deal with other forms of substance abuse common in this population. Overall, we believe the treatment represents an important step towards the development of empirically based and effective treatments for cocaine dependence.

Behavior Therapy↗
PubMed1994

Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities.

Many of the symptoms of nicotine withdrawal are similar to those of other drug withdrawal syndromes: anxiety, awakening during sleep, depression, difficulty concentrating, impatience, irritability/anger and restlessness. Slowing of the heart rate and weight gain are distinguishing features of tobacco withdrawal. Although nicotine withdrawal may not produce medical consequences, it lasts for several weeks and can be severe in some smokers. Like most other drug withdrawals, nicotine withdrawal is time-limited, occurs in non-humans, is influenced by instructions/expectancy and abates with replacement therapy and gradual reduction. Unlike some other drug withdrawal syndromes, protracted, neonatal or precipitated withdrawal does not occur. Whether nicotine withdrawal is associated with tolerance, acute physical dependence, greater duration and intensity of use, rapid reinstatement, symptom stages, cross-dependence with other nicotine ligands, reduction by non-pharmacological interventions and genetic influences is unclear. Whether nicotine withdrawal plays a major role in relapse to smoking has not been established but this is also true for other drug withdrawal syndromes.

Animals↗
PubMed1994

A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification.

Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicit-opioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.

Administration, Sublingual↗
PubMed1994

Alcohol dependence and simultaneous cocaine and alcohol use in cocaine-dependent patients.

Alcohol use and associated factors were studied in 124 consecutive cocaine-dependent admissions to an outpatient substance abuse clinic. Two analyses were conducted: First, those who did and did not meet criteria for current alcohol dependence were compared on sociodemographic and drug use characteristics. Second, patients who reported simultaneous cocaine and alcohol use on > 50% vs. < or = 50% of the occasions that they used cocaine were compared using the same dependent measures. Fifty-seven percent of patients met criteria for current alcohol dependence. Those with and without alcohol dependence did not differ on any sociodemographic characteristics, but those with dependence scored higher on the alcohol and family subscales of the Addiction Severity Index, the Michigan Alcoholism Screening Test, and measures of alcohol use, and were more likely to use cocaine and alcohol simultaneously, to use cocaine with friends and in social settings, and were more likely to report financial difficulties and unwanted sexual relations as adverse consequences of their cocaine use. Sixty-four percent of patients reported > 50% simultaneous cocaine and alcohol use. The two groups did not differ on any sociodemographic characteristics, but those reporting greater simultaneous use were more likely to be alcoholic, scored higher on most measures of alcohol use, and were more likely to report using cocaine with friends and in social settings. The only other differences observed between the two groups were fewer reports of seizures or difficulty concentrating in the group reporting greater simultaneous use. The present results confirm prior reports on the widespread prevalence of alcohol dependence among cocaine-dependent patients and extend them by providing new information on the prevalence and other characteristics of simultaneous cocaine and alcohol use.

Adult↗
PubMed1993

A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers.

Two experiments were conducted to assess the acute behavioral effects of triazolam and temazepam in healthy, non-drug abusing men in double-blind, placebo-controlled, crossover trials, where all subjects received all possible doses. These drugs were compared to examine allegations that triazolam produces greater behavioral impairment than temazepam. Drug effects were assessed during 4-h sessions using measures of recall, learning, psychomotor performance, and subject ratings assessing drug effects and abuse potential. In experiment 1, triazolam (0.25 and 0.5 mg/70 kg) produced greater behavioral impairment than temazepam (15 and 30 mg/70 kg). However, triazolam also produced greater increases than temazepam in subject ratings of drug strength, drunkenness and sleepiness, suggesting the dose ranges compared may not have been clinically equivalent. Experiment 2 was conducted to assess whether a higher dose of temazepam than tested in experiment 1 would produce levels of behavioral impairment comparable to those observed with triazolam in experiment 1. In experiment 2, the temazepam dose was increased to 60 mg/70 kg while the triazolam dose was 0.5 mg/70 kg which was the highest dose tested in experiment 1. These doses produced comparable increases in subject ratings of drug strength, drunkenness and sleepiness, but temazepam produced significantly more behavioral disruption than triazolam. These findings do not support the position that triazolam produces greater behavioral impairment than temazepam, and may even suggest that across a wide range of doses triazolam is less disruptive than temazepam.

Adult↗
PubMed1993

Drug discrimination by humans compared to nonhumans: current status and future directions.

In drug discrimination (DD) procedures, behavior is differentially reinforced depending on the presence or absence of specific drug stimuli. The DD paradigm has been widely adopted by behavioral pharmacologists because of its specificity of stimulus control, concordance with drug action at cellular levels and its use as a preclinical model of subject-rated effects in humans. With the successful extension of DD to humans, a comparison of human and nonhuman DD will help place each in the context of the other. Twenty-eight studies of DD in humans are reviewed, including studies of amphetamine, opioid, benzodiazepine, caffeine, nicotine, marijuana and ethanol discriminative stimuli. Comparison of procedures between studies in humans and nonhumans reveals a common tradition, except the use of instructions appears to facilitate greatly DD acquisition in humans. Findings were qualitatively similar between humans and nonhumans. Potency relationships were quantitatively similar between humans and most, but not all, other species. Areas of human DD needing additional empirical evaluation include the influence of instructions, the effects of training dose and the effects of antagonists. Additionally, antihistamines, barbiturates, nicotine and marijuana are under-represented in human DD.

Animals↗
PubMed1993

Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans.

Subjects received acute doses of orally administered alcohol (0-1.0 g/kg) and intranasal cocaine (4-96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable.

Administration, Intranasal↗
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↗
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↗