Biomedical subjects

W K Bickel

Publications and source records attributed to W K Bickel.

At least 19 recordsLinked to original sources

PubMed2003

The behavioral economics of cigarette smoking: The concurrent presence of a substitute and an independent reinforcer.

The present study examined the consumption of cigarettes and two alternative reinforcers in dependent smokers. Cigarette price (response requirement) increased across sessions while alternatives were available at a fixed price in four phases of availability: (1). cigarettes alone; (2). cigarettes and nicotine gum; (3). cigarettes and money; and (4). cigarettes, nicotine gum, and money. Cigarette consumption decreased with increasing price throughout. In the cigarette and nicotine gum phase, nicotine gum consumption increased with cigarette price, indicating nicotine gum to be a substitute for cigarettes. In the cigarette and money phase, money consumption increased slightly with cigarette price, indicating money to be an independent reinforcer for cigarettes. When all three reinforcers were present, money again served as an independent reinforcer. During this phase, nicotine gum consumption increased marginally, but the small magnitude of increase suggests that nicotine gum functioned as an independent reinforcer rather than a substitute. Cigarette consumption decreased modestly when nicotine gum was available, and to a larger extent when money or both alternatives were available. The results highlight the potential for an independent reinforcer such as money to be more effective at reducing drug use than a pharmacological substitute.

Behavior, Addictive↗

PubMed2002

Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users.

This study compared the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate with placebo in healthy volunteers. Sixteen non-dependent light drug users participated in six experimental sessions, receiving placebo, atomoxetine (20, 45 and 90 mg) and methylphenidate (20 and 40 mg) using a double-blind, Latin square design. Subjective drug effects were assessed using Visual Analog Scales (VAS), the Addiction Research Center Inventory (ARCI) and Adjective Rating Scales (ARS). Psychomotor performance was evaluated using the Digit Symbol Substitution Test (DSST). Physiological measures were also collected throughout the sessions. Assessments were conducted before drug administration and 30, 60, 90, 120, 150, 180 and 240 min following dosing. Forty milligrams methylphenidate produced significant increases on the stimulant portions of the VAS and ARS and the benzedrine, amphetamine, morphine-benzedrine and lysergic acid diethylamine (LSD) subscales of the ARCI relative to placebo. Ninety mg atomoxetine was reported to be unpleasurable relative to placebo as indicated by significant increases on the 'bad' and 'sick' portions of the VAS, and on the LSD subscale of the ARCI. Compared with placebo, both methylphenidate doses significantly increased systolic blood pressure (BP) and heart rate (HR). For atomoxetine, 90 mg increased diastolic BP, 45 and 90 mg increased systolic BP, and all three doses increased HR relative to placebo. Neither compound produced significant differences from placebo on DSST performance. These results suggest that atomoxetine does not induce subjective effects similar to methylphenidate and suggest that it is unlikely that atomoxetine will have abuse liability.

Adolescent↗

PubMed2001

Limits to buprenorphine dosing: a comparison between quintuple and sextuple the maintenance dose every 5 days.

The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent outpatients. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled, cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n=4) and 8 mg/70 kg (n=10). After a stabilization period of daily maintenance administration, subjects received quintuple (5x daily maintenance dose) and sextuple (6x daily maintenance dose) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily. Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens. There was no evidence, however, that those subjective ratings of withdrawal differed between the two regimens. Thus, these data suggest that sextuple buprenorphine dosing, administered every 5 days, does not abate opioid-withdrawal beyond 96 hours.

Adult↗

PubMed2001

Effects of alprazolam, caffeine, and zolpidem in humans trained to discriminate triazolam from placebo.

This study compared the discriminative stimulus effects of zolpidem, a nonbenzodiazepine hypnotic, to benzodiazepines. Eight participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. The discriminative stimulus effects, self-reported subjective effects, and performance effects of triazolam (0.05-0.35 mg/70 kg), alprazolam (0.25-1.75 mg/70 kg), zolpidem (2.5-35 mg/70 kg) and caffeine (75-525 mg/70 kg) were assessed under two-response and novel-response drug discrimination procedures. Under the two-response procedure, triazolam, alprazolam and zolpidem fully substituted for triazolam and caffeine did not. Under the novel-response procedure, triazolam and alprazolam substituted for triazolam and zolpidem partially substituted for triazolam. Zolpidem, but not triazolam or alprazolam, also produced some novel responding. Caffeine produced both placebo-appropriate and novel responding. The self-reported effects of triazolam, alprazolam and zolpidem were similar. Overall, zolpidem produced similar, but not identical, effects as the benzodiazepines.

Adolescent↗

PubMed2001

Toward a behavioral economic understanding of drug dependence: delay discounting processes.

Behavioral economics examines conditions that influence the consumption of commodities and provides several concepts that may be instrumental in understanding drug dependence. One such concept of significance is that of how delayed reinforcers are discounted by drug dependent individuals. Discounting of delayed reinforcers refers to the observation that the value of a delayed reinforcer is discounted (reduced in value or considered to be worth less) compared to the value of an immediate reinforcer. This paper examines how delay discounting may provide an explanation of both impulsivity and loss of control exhibited by the drug dependent. In so doing, the paper reviews economic models of delay discounting, the empirical literature on the discounting of delayed reinforcers by the drug dependent and the scientific literature on personality assessments of impulsivity among drug-dependent individuals. Finally, future directions for the study of discounting are discussed, including the study of loss of control and loss aversion among drug-dependent individuals, the relationship of discounting to both the behavioral economic measure of elasticity as well as to outcomes observed in clinical settings, and the relationship between impulsivity and psychological disorders other than drug dependence.

Humans↗

PubMed2001

Examining the limits of the buprenorphine interdosing interval: daily, every-third-day and every-fifth-day dosing regimens.

AIMS: Opioid-dependent outpatients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged. These studies compared opioid withdrawal symptoms during 24-, 72-, and 120-hour buprenorphine dosing regimens and evaluated participants' preferences for these different dosing regimens. PARTICIPANTS: Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg (n = 14) or 8 mg/70 kg (n = 19) of liquid buprenorphine. METHODS: In Study I participants received, in a random order, three dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg) and quintuple the daily maintenance dose every 120 hours (20 or 40 mg/70 kg). Doses were administered under double-blind procedures, and placebos were administered on the interposed days during the latter two regimens. Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose. In Study II, a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens. FINDINGS: Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies. In the choice phase of Study II, only one participant (7%) chose quintuple-every-fifth-day dosing over all other dosing options. CONCLUSIONS: These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided.

Adult↗

PubMed2001

Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis.

A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine-containing and de-nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine-containing and de-nicotinized cigarettes by assessing the effects of alternative non-drug reinforcement on self-administration of both cigarette types. Eight human subjects responded on a progressive-ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine-containing and de-nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non-drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non-drug reinforcer. These data suggest the importance of further examination of non-pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non-drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de-nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.

Adult↗

PubMed2001

Behavioral economics of human drug self-administration: progressive ratio versus random sequences of response requirements.

Progressive-ratio (PR) schedules have been used widely to examine the relationship between drug consumption and drug price (i.e. demand curves) in the study of the behavioral economics of drug abuse. Sequential effects produced by the increasing response requirements of progressive-ratio schedules might influence the shape of demand curves for drug reinforcers. This study compared progressive ratio schedule and random sequences of ratio requirements, each incremented across sessions in a within-subject design, to determine if they produced similar behavioral economic and traditional measures of reinforcer efficacy. Self-administration of standardized cigarette puffs (70 cc each) was studied with eight smokers. Puffs were available at nine ratio requirements (e.g. 3, 100, 300, 600, 1500, 3000, 6000, 12000, 24000 responses/three puffs), presented in ascending (progressive-ratio schedule) or random sequence across daily sessions. The parameter estimates obtained on measures of reinforcing efficacy (e.g. breakpoint, peak response rates, elasticity of demand) were similar for both methods of incrementing prices. We found no evidence that PR and random sequences of fixed-ratio (FR) schedules, incremented across daily sessions, resulted in different demand curves.

Adult↗

PubMed2001

Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans.

Although the rate of onset of a drug effect is commonly believed to contribute to a drug's abuse liability, only a few systematic experimental studies have been conducted examining this notion. The present study determined the profile of physiological, psychomotor, and self-reported effects of infusion rate (a key means of manipulating onset of drug action) of intravenously administered morphine, the prototypical analgesic with a known abuse liability in human participants. Two doses of morphine sulfate (5 and 10 mg/70 kg, i.v.) and a placebo dose (0 mg/70 kg, i.v.) were administered to healthy volunteers under three infusion rates (2 min bolus, 15 min, and 60 min). Faster infusions of morphine produced greater positive subjective effects than slower infusions on visual analog scale measures of good drug effect, drug liking, and high. Faster infusions also resulted in greater self-reported drug effects and opioid agonist effects, without producing significant physiological or psychomotor impairment. Importantly, faster rates of drug infusion produced significantly higher morphine plasma levels than slower rates, and morphine plasma levels followed a similar pattern and timing of peak effect as the self-reported effects of the drug. Moreover, morphine produced dose-dependent increases in self-reported drug effects, opioid agonist effects, and morphine plasma levels in the study. Results suggest that the pharmacokinetic properties of a drug, including the dosage administered and the rate of at which it is administered may function to jointly affect the abuse liability of the drug.

Adolescent↗

PubMed2000

Needle sharing in opioid-dependent outpatients: psychological processes underlying risk.

Needle sharing contributes to the spread of the human immunodeficiency virus and other health concerns and remains a persistent problem among injection drug users. We determined whether needle sharing may be related to the discounting of the value of delayed outcomes. Outpatients in treatment for heroin dependence indicated preference for immediate versus delayed hypothetical monetary and heroin outcomes in a titration procedure that determined indifference points at various delays. The degree to which the delayed outcomes lost value was estimated with a nonlinear decay model. Participants who agreed to share a needle in a scenario (N=15) discounted delayed money more steeply than did the nonsharing group (N=17). Both groups discounted delayed heroin more steeply than delayed money. Persistent needle sharing may be related to the relative inability of delayed outcomes to impact current behavior. Training to mitigate the effect of delay on outcome value may offer reductions in needle sharing and drug abuse.

Adult↗

PubMed2000

Gender differences in hostility of opioid-dependent outpatients: role in early treatment termination.

The purpose of this study was to evaluate gender differences in hostility and the role of hostility in predicting early treatment termination of opioid-dependent outpatients. Demographic characteristics and Addiction Severity Index (ASI) ratings were collected from 104 patients (68 males and 36 females) at intake to a buprenorphine treatment program. Hostility was assessed using the Buss-Durkee Hostility Scale. Compared to male opioid-dependent patients, females scored significantly higher on this scale. Early treatment termination was defined as remaining in treatment < 30 days, and 13% percent of males and 25% of females were classified as early terminators. Stepwise logistic regression identified predictors of early treatment termination. Severity of legal and employment problems and the interaction between hostility and gender predicted early treatment termination status. Patients with less severe legal problems and patients with greater employment problems were more likely to terminate early from treatment. Higher levels of hostility predicted early treatment termination of female patients, but hostility levels were not associated with treatment termination in male patients. Results from this study show that female heroin addicts have high levels of hostility and suggest that hostility may be an important predictor of premature discharge from opioid substitution programs, especially among women.

Adult↗

PubMed2000

Deconstructing relative reinforcing efficacy and situating the measures of pharmacological reinforcement with behavioral economics: a theoretical proposal.

BACKGROUND: Relative reinforcing efficacy has been assumed to be a homogeneous phenomenon referring to the behavior-strengthening or behavior-maintaining effects of a drug reinforcer. However, a variety of studies suggest that relative reinforcing efficacy may be heterogeneous. OBJECTIVES: The purpose of this theoretical proposal is to examine the difficulties associated with this conception of reinforcing efficacy and to explore whether relative reinforcing efficacy is a homogenous concept or whether it is composed of several functionally related heterogeneous phenomena. In examining this issue, we explore whether behavioral economic theory may address some of the challenges to the current conception of relative reinforcing efficacy and use this theory to suggest how the differing measures of reinforcing efficacy may relate to one another. RESULTS: Results indicate that peak-response rate and breakpoint are related to the economic measure of maximal output and elasticity of demand, respectively. Preference is related to and predicted by the relative location of the demand curves obtained under single schedule conditions. This behavioral economic analysis may provide a theoretical understanding of reinforcement that can reconcile results of studies that both support and fail to support the notion of reinforcing efficacy as a homogenous phenomenon. CONCLUSIONS: If this theoretical proposal is validated by additional studies, then like other natural phenomena found to be heterogeneous, the study of drug reinforcers may require the adoption of several new scientific terms, such as those used in behavioral economics, each of which has analytical precision and refers to homogeneous phenomena.

Animals↗

PubMed2000

Celebrating the decade of behavior: introduction to special issue.

This special issue represents a joint effort by the journal Experimental and Clinical Psychopharmacology and the American Psychological Association's Division of Psychopharmacology and Substance Abuse to celebrate the "Decade of Behavior: 2000-2100" initiative. The Decade of Behavior initiative seeks to underscore the importance of behavioral science to broadening understanding and offering solutions to many of society's most challenging problems. Contained in this special issue are commentaries by 3 Institute directors from the National Institutes of Health, 4 excellent critical reviews of various aspects of contemporary psychopharmacology research, and a series of 9 excellent original research reports. This series of articles bodes well for the health of psychopharmacology and substance abuse research and offers a fitting salute to this important initiative.

Animals↗

PubMed2000

A comparison of four buprenorphine dosing regimens using open-dosing procedures: is twice-weekly dosing possible?

AIMS: To compare opioid withdrawal symptoms during 24-, 48-, 72- and 96-hour buprenorphine dosing regimens and to evaluate subjects' preferences for these different dosing schedules. SUBJECTS: Fourteen opioid-dependent subjects participated in this study. They received daily sublingual maintenance doses of 4 mg/70 kg (n = 4) or 8 mg/70 kg (n = 10) of buprenorphine. INTERVENTION: In the first study subjects received, in a random order, four dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), double the daily maintenance dose every 48 hours (8 or 16 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg), and quadruple the daily maintenance dose every 96 hours (16 or 32 mg/70 kg). Measures of subjective and observer opioid withdrawal symptoms were assessed prior to receipt of each dose. In a second study, subjects chose between the different dosing regimens. FINDINGS: Some withdrawal ratings increased during the less frequent dosing schedules in the first study. In the second study, 46% of subjects preferred the quadruple-every-fourth-day dosing regimen over every other option, and only 14% preferred to be dosed daily. CONCLUSIONS: These results suggest that some opioid-dependent outpatients are willing and able to endure the withdrawal symptoms associated with less than daily dosing, and a twice-weekly dosing regimen may be possible.

Adult↗

PubMed2000

Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine.

The purpose of this study was to assess changes in liver enzyme levels among opioid-dependent patients treated with buprenorphine. Liver enzyme levels were evaluated among 120 individuals before treatment and following a minimum of 40 days of buprenorphine treatment (2, 4, or 8 mg/70 kg/day). Among patients with a history of hepatitis, AST and ALT levels significantly increased (p < .05) with buprenorphine treatment. The odds of observing an increase in AST were determined to be dependent upon buprenorphine dose (p < .05; odds ratio = 1.23 per 1 mg increase in dose). These results suggest that liver enzyme levels should be monitored carefully when patients with hepatitis are treated with buprenorphine.

Adult↗

PubMed2000

Nicotine gum as a substitute for cigarettes: a behavioral economic analysis.

The present experiment attempted to identify a substitute for cigarette smoking in a laboratory analog of the behavioral economics of drug dependence. The interaction between cigarette consumption and nicotine gum consumption was examined with eight human smokers by increasing the price of cigarettes (i.e. the number of responses required to obtain puffs) across sessions, while the price of concurrently available nicotine gum remained constant. In another phase, the price of nicotine gum was increased while the price of concurrently available cigarettes remained constant. To determine whether the presence of concurrently available nicotine gum influenced cigarette consumption, we also examined the effect of increasing the price of cigarettes on cigarette consumption without available nicotine gum. When cigarettes and nicotine gum were concurrently available, increases in the price of cigarettes increased consumption of nicotine gum. When the price of nicotine gum increased while the price of cigarettes remained constant, smokers nearly exclusively consumed cigarettes. The presence or absence of nicotine gum did not affect the relation between cigarette consumption and cigarette price. The results suggest that nicotine gum can maintain operant behavior of smokers in the laboratory and can function, in a behavioral economic sense, as a weak substitute for cigarette puffs. As a result, nicotine gum may be useful in human laboratory studies of the behavioral economics of reinforcer interactions and their role in drug dependence.

Adult↗

PubMed2000

Three predictions of the economic concept of unit price in a choice context.

Economic theory makes three predictions about consumption and response output in a choice situation: (a) When plotted on logarithmic coordinates, total consumption (i.e., summed across concurrent sources of reinforcement) should be a positively decelerating function, and total response output should be a bitonic function of unit price increases; (b) total consumption and response output should be determined by the value of the unit price ratio, independent of its cost and benefit components; and (c) when a reinforcer is available at the same unit price across all sources of reinforcement, consumption should be equal between these sources. These predictions were assessed in human cigarette smokers who earned cigarette puffs in a two-choice situation at a range of unit prices. In some sessions, smokers chose between different amounts of puffs, both available at identical unit prices. Individual subjects' data supported the first two predictions but failed to support the third. Instead, at low unit prices, the relatively larger reinforcer (and larger response requirement) was preferred, whereas at high unit prices, the smaller reinforcer (and smaller response requirement) was preferred. An expansion of unit price is proposed in which handling costs and the discounted value of reinforcers available according to ratio schedules are incorporated.

Adult↗

PubMed1999

Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers.

RATIONALE: Impulsivity is implicated in drug dependence. Recent studies show problems with alcohol and opioid dependence are associated with rapid discounting of the value of delayed outcomes. Furthermore, discounting may be particularly steep for the drug of dependence. OBJECTIVES: We determined if these findings could be extended to the behavior of cigarette smokers. In particular, we compared the discounting of hypothetical monetary outcomes by current, never, and ex-smokers of cigarettes. We also examined discounting of delayed hypothetical cigarettes by current smokers. METHODS: Current cigarette smokers (n=23), never-smokers (n=22) and ex-smokers (n=21) indicated preference for immediate versus delayed money in a titration procedure that determined indifference points at various delays. The titration procedure was repeated with cigarettes for smokers. The degree to which the delayed outcomes were discounted was estimated with two non-linear decay models: an exponential model and a hyperbolic model. RESULTS: Current smokers discounted the value of delayed money more than did the comparison groups. Never- and ex-smokers did not differ in their discounting of money. For current smokers, delayed cigarettes lost subjective value more rapidly than delayed money. The hyperbolic equation provided better fits to the data than did the exponential equation for 74 out of 89 comparisons. CONCLUSIONS: Cigarette smoking, like other forms of drug dependence, is characterized by rapid loss of subjective value for delayed outcomes, particularly for the drug of dependence. Never- and ex-smokers could discount similarly because cigarette smoking is associated with a reversible increase in discounting or due to selection bias.

Adult↗