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Biomedical subjects

S T Higgins

Publications and source records attributed to S T Higgins.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Alternate-day dosing during buprenorphine treatment of opioid dependence.

Thirteen opioid-dependent outpatients participated in a double-blind, placebo-controlled, crossover trial. Twenty-one days of daily sublingual buprenorphine administration were compared to 21-days of alternate-day buprenorphine administration where patients received twice their daily maintenance dose every other day with placebo on the interposed day. Observer- and subject-rated measures of opioid agonist and withdrawal effects, pupillary diameter, and dose identifications were collected daily. Ten subjects (77%) completed the study (n = 6, 4 mg/70 kg; n = 4, 8 mg/70 kg); 8 subjects (62%) participated in a second crossover. Sixteen of seventeen measures of opioid agonist and withdrawal effects obtained during alternate-day administration did not differ significantly from those obtained during daily dosing in the ten subjects completing the study. The only significant difference observed was in subject-rated agonist effects, which were significantly lower during alternate-day than daily administration. No differences were observed between treatments on any measure for the eight subjects completing a second crossover. These data suggest that buprenorphine can be administered safely every 48 hours by doubling the maintenance dose. This alternate-day schedule permits patients to attend the clinic less frequently without the risk of diversion associated with take-home doses, may be cost-effective for programs, and may be useful in settings in which travel to the clinic is a barrier to treatment.

Administration, Sublingual↗

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↗

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↗

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↗

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↗

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↗

A behavioral economic analysis of concurrently available money and cigarettes.

In economic terms, consumption of a reinforcer is determined by its price and the availability and price of other reinforcers. This study examined the effects of response-requirement (i.e., price) manipulations on the self-administration of two concurrently available reinforcers. Six cigarette smokers participated in 4-hr sessions in which money and puffs on a cigarette were concurrently available according to fixed-ratio schedules of reinforcement. Once stable responding was obtained with both reinforcers available at Fixed Ratio 100, the response requirement for one reinforcer was systematically varied (Fixed Ratio 1,000 and 2,500), while the other reinforcer remained scheduled at Fixed Ratio 100. Increasing the fixed-ratio size for a reinforcer decreased its consumption, with a greater decrease occurring for monetary reinforcement. This finding was quantified in economic terms as own-price elasticity, with elasticity coefficients greater for money than cigarettes. The effects of fixed-ratio size on response output also differed across the two reinforcers. Although greater responding occurred for money at Fixed Ratio 100, increases in fixed-ratio size (for money) decreased responding for money, whereas the same increase in fixed-ratio size (for puffs) increased responding for puffs. Finally, increasing the fixed-ratio size for one reinforcer had little effect on consumption of the other concurrently available reinforcer. This finding was quantified as cross-price elasticity, with elasticity coefficients near 0.0 for most subjects, indicating little or no reinforcer interaction. The results indicate that the reinforcing effects of cigarettes and money in the setting studied here differed, and that the effects produced by changing the price of one reinforcer did not interact with the consumption of the other concurrently available reinforcer.

Adolescent↗

Participation of significant others in outpatient behavioral treatment predicts greater cocaine abstinence.

The present study was conducted to identify predictors of cocaine abstinence during outpatient behavioral treatment for cocaine dependence. Subjects were 52 cocaine-dependent adults. Stepwise logistic regression was used to identify predictors of abstinence during a 12-week treatment program. Demographic, drug use, and other subject characteristics were examined. The single best predictor of cocaine abstinence was whether a significant other participated in treatment. The odds of achieving a criterion level of cocaine abstinence were approximately 20 times greater for subjects who had a significant other participate in treatment. Importantly, significant others participated in a structured form of relationship counseling and behavioral contracting that is well specified and can be readily tested in a prospective, randomized trial. Considering the pressing need for the development of effective treatments for cocaine dependence, such a trial merits consideration.

Adult↗

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↗

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↗

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↗

Relationship between intravenous use and achieving initial cocaine abstinence.

This study assessed whether route of cocaine administration (intravenous vs. intranasal) influences cocaine abstinence during the first 6 weeks of outpatient treatment. Fifty-nine persons received behavioral treatment or standard drug counselling in an outpatient clinic. Based on information collected at intake, intravenous users had fewer years of education, were employed in less skilled jobs, were less likely to be married, reported more negative consequences from cocaine use, reported using more cocaine per occasion and spent more money on cocaine per week than intranasal users. Intravenous and intranasal users did not differ significantly in the average duration of continuous cocaine abstinence (mean = 2.6 vs. mean = 3.3 weeks achieved during 6 weeks of treatment). The duration of abstinence between intravenous and intranasal users was equal in the behavioral treatment (mean = 4.2). In standard treatment the average duration was less among intravenous than intranasal users (mean = 0.9 vs. mean = 2.4), but that difference did not achieve statistical significance. Hepatitis and employment instability were associated with shorter periods of cocaine abstinence among intravenous users, whereas employment instability, lower job skill level, drug use severity and reports of memory loss were associated with shorter periods of cocaine abstinence among intranasal users. These results indicate that i.v. cocaine users can achieve a period of initial abstinence in an outpatient setting comparable to the duration of typical inpatient hospitalizations, although special types of outpatient treatment may be necessary to obtain a positive outcome.

Administration, Intranasal↗

Behavioral economics: a novel experimental approach to the study of drug dependence.

Drug abuse and dependence are among the most important problems facing society today. Understanding the determinants of drug abuse has been advanced by a considerable quantity of research on environmental and pharmacological factors that control drug taking in a variety of settings and species. Behavioral economics, which is the application of economic principles to the behavior of the individual, may have the potential to integrate a number of these empirical observations in a novel quantitative framework. In this paper the utility of behavioral economics for the study of drug dependence is reviewed. Specifically, we reviewed (i) the parsimony behavioral economics affords via the integration of variables, (ii) a ubiquitous behavioral process it has identified, (iii) the precise quantification of that behavioral process and its predictive utility, (iv) a novel independent variable suggested by behavioral economics, and (v) the utility of behavioral economic notions for the process of medication development. We conclude that behavioral economics provides a novel conceptual framework that has utility for the study of drug dependence.

Animals↗

Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships.

In four prior studies, caffeine (100 mg) self-administration was assessed by greater self-administration of caffeinated coffee than decaffeinated coffee and caffeine withdrawal was assessed by placebo substitution using six double-blind tests in each subject. This paper collates data across these studies to examine the incidence and predictors of the occurrence of caffeine self-administration and withdrawal. Caffeine self-administration occurred in 31% of subjects when a consistency criterion was used (n = 41) and 27% when a statistical criterion was used. Caffeine withdrawal occurred in 35% and 49% of subjects with each criteria (n = 37). Subjects who had withdrawal headaches and drowsiness were 2.3-2.6 times more likely to self-administer the caffeinated coffee. Several variables (e.g., average caffeine intake) did not predict caffeine self-administration or withdrawal.

Adult↗

Nicotine and caffeine use in cocaine-dependent individuals.

Nicotine and caffeine use in 87 cocaine-dependent persons seeking treatment at an outpatient clinic were compared to use of those substances in a matched general population sample (n = 78). The prevalence of cigarette smoking was significantly greater in the cocaine-dependent sample (75% vs. 22%). Within the cocaine-dependent sample, smokers were younger, less educated, employed in lesser skilled jobs, and reported an earlier onset and more frequent use of cocaine. The prevalence of caffeine use was significantly less in the cocaine-dependent group (68% vs. 83%), although, among caffeine users, the cocaine group drank significantly more caffeinated beverages per day than matched controls (4.9 vs. 3.3). Interestingly, regular caffeine use was associated with less frequent cocaine use within the cocaine-dependent sample. To our knowledge, this study is the first to report on prevalence of smoking and caffeine use among cocaine-dependent individuals, and suggests that use of these other substances may influence the onset and pattern of cocaine use.

Ambulatory Care↗