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Biomedical subjects

W K Bickel

Publications and source records attributed to W K Bickel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of response requirement and the availability of an alternative reinforcer on cigarette smoking by schizophrenics.

Cigarette smoking and other forms of drug abuse are more prevalent among schizophrenics than the general population. Despite the clinical importance of this problem, there has been relatively little experimental study of schizophrenic drug use. We examined under controlled laboratory conditions the effects of response requirement and the availability of an alternative (monetary) reinforcer on cigarette smoking by schizophrenics. Subjects were six heavy smokers with diagnoses of schizophrenia or schizoaffective disorder. Before each session, subjects provided carbon monoxide samples indicating recent smoking abstinence. During 3-h sessions, subjects obtained opportunities to smoke (2 puffs/opportunity) under a fixed ratio (FR) schedule of reinforcement, which varied across sessions from FR50 to FR6400. In half of the sessions, subjects also were able to earn a small amount of money ($0.25/ratio completed) under an FR400 schedule. Increasing the response requirement for smoking decreased smoking and increased smoking-maintained responding. The availability of the monetary reinforcer decreased smoking and smoking-maintained responding by approximately half. These results are consistent with those seen previously in community volunteers without major mental illness studied under the same experimental conditions, suggesting that smoking by these two populations is controlled, at least in part, by a common set of determinants.

Adult↗
PubMed1999

Buprenorphine dosing every 1, 2, or 3 days in opioid-dependent patients.

RATIONALE: Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown. OBJECTIVES: To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication. METHODS: Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21-22 days. Self report and observer measures were taken at 24-h intervals. RESULTS: No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed. CONCLUSIONS: These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.

Adult↗
PubMed1999

Comparing the reinforcing efficacy of nicotine containing and de-nicotinized cigarettes: a behavioral economic analysis.

RATIONALE: Smoking-related respiratory stimuli produced by de-nicotinized cigarettes may function as conditioned reinforcers, but behavioral data on such reinforcing effects are limited. OBJECTIVES: The present experiment compared the reinforcing efficacy of cigarettes that provided only smoking-related stimuli (de-nicotinized cigarettes) and cigarettes that provided both smoking-related stimuli and nicotine. METHODS: Eight human subjects responded on a progressive-ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. In one phase, the breakpoints, number of puffs earned per session, peak response rates, ratio producing peak response rates, and the elasticity of demand for cigarette puffs were compared for nicotine-containing and de-nicotinized cigarettes when each cigarette type was the only one available. In another phase, subjects chose between the two cigarette types at some of the prices examined in the previous phase. RESULTS: Nicotine-containing and de-nicotinized cigarettes produced similar measures of reinforcing efficacy when each was presented alone, but there was a strong preference for nicotine-containing cigarettes when subjects were given a choice. CONCLUSIONS: These data support suggestions that smoking-produced sensory stimuli may function as conditioned reinforcers and that the relative reinforcing efficacy of cigarettes is determined by the combined effects of the nicotine/conditioned reinforcing complex provided by smoking.

Adult↗
PubMed1999

A comparison of four buprenorphine dosing regimens in the treatment of opioid dependence.

OBJECTIVES: This study compared 24-, 48-, 72-, and 96-hour buprenorphine dosing regimens in opioid-dependent outpatients. METHODS: Fourteen subjects received buprenorphine in a double-blind, placebo-controlled crossover trial. Daily sublingual maintenance doses were 4 mg/70 kg (n = 5) and 8 mg/70 kg (n = 9). After a stabilization period of maintenance administration, subjects received, in a random order, four dosing regimens for five repetitions of each regimen: a maintenance dose every 24 hours, a doubled maintenance dose every 48 hours, a tripled maintenance dose every 72 hours, and a quadrupled maintenance dose every 96 hours. In the latter three dosing regimens, subjects received placebo on the interposed day(s). Study participation was contingent on opioid abstinence and daily clinic attendance. Measures of subjective opioid agonist and withdrawal effects were assessed daily. RESULTS: Relative to standard maintenance dosing, none of the higher doses induced agonist effects. Changes in indices of subjective withdrawal effects were noted as the time since the last active dose increased during intermittent dosing regimens, but the magnitude of these effects was relatively low and was comparable to those found in other alternate-day dosing studies. CONCLUSIONS: These results support the feasibility and safety of twice weekly buprenorphine dosing regimens.

Adult↗
PubMed1999

The novel-response procedure in humans.

The novel-response drug discrimination procedure is one of several three-choice procedures developed to address interpretational difficulties that can occur under standard two-response procedures. The novel-response procedure is unique among three-choice discrimination procedures by using instructions, rather than explicit training procedures. With the novel-response procedure, participants are trained under a standard two-response (drug vs. placebo) discrimination, and then instructed that in the presence of a drug stimulus unlike either of the training drugs, responses should be made on the novel-response alternative. Several studies have assessed the utility of the novel-response procedure by comparing effects under a standard two-response and the novel-response procedure in participants trained to discriminate triazolam from placebo. Results indicate that the novel-response procedure can increase the selectivity of both placebo- and drug-appropriate responding, and in this way, allows for finer distinctions to be made among sedatives than a standard two-response procedure.

Anti-Anxiety Agents↗
PubMed1999

Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls.

Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ($11-$80) available immediately and larger rewards ($25-$85) available after delays ranging from 1 week to 6 months. Participants had a 1-in-6 chance of winning a reward that they chose on one randomly selected trial. Delay-discounting rates were estimated from the pattern of participants' choices. The discounting model of impulsiveness (Ainslie, 1975) implies that delay-discounting rates are positively correlated with impulsiveness. On average, heroin addicts' discount rates were twice those of controls (p = .004), and discount rates were positively correlated with impulsivity as measured by self-report questionnaires (p < .05). The results lend external validity to the delay-discounting rate as a measure of impulsiveness, a characteristic associated with substance abuse.

Adult↗
PubMed1999

Buprenorphine dose self-selection: effects of an alternative reinforcer, behavioral economic analysis of demand, and examination of subjective drug effects.

Buprenorphine (BUP)-maintained patients were first exposed to various BUP doses and then chose between BUP doses and money. In the choice phase, they had 10 units exchangeable for units of BUP (constant at 3 mg/unit) or money (varied from $0.30 to $20/unit). They chose BUP exclusively (30 mg) when the money alternative was low. As available money increased, they selected lower daily BUP doses (down to 3 mg). An economic analysis indicated demand for BUP was inelastic; changes in drug intake were proportionally lower than changes in price. Subjective reports of agonist and withdrawal effects increased > 200% when high and low BUP doses, respectively, were given during the exposure phase. In the choice phase, subjective drug effects were constant regardless of the BUP dose selected. Thus, BUP dose selection varies with the magnitude of alternative reinforcers, and subjective drug effects depend on whether doses are self- or experimenter-selected.

Adult↗
PubMed1999

Discounting of delayed rewards in opioid-dependent outpatients: exponential or hyperbolic discounting functions?

Recent theories of substance abuse have used value discounting of delayed rewards to partly explain the decision to take drugs. Normative-economic theory holds that an exponential function describes the effects of delay on discounting, whereas the matching law posits a hyperbolic discounting function. The ability of these functions to describe 18 human heroin-dependent individuals' monetary- and heroin-reward delay-discounting functions was assessed. In the 1st condition, participants chose between immediate and delayed hypothetical monetary rewards. Delayed rewards were $1,000, and the immediate reward amount was adjusted until choices reflected indifference. In the 2nd condition, participants chose between immediate and delayed heroin (the delayed amount was that which each participant reported he or she could purchase with $1,000). The hyperbolic function produced significantly higher R2 values and significantly lower sums of squared error values. Consistent with previous findings, delayed heroin rewards were discounted at a significantly higher rate than were delayed monetary rewards.

Adult↗
PubMed1999

Modeling drug consumption in the clinic using simulation procedures: demand for heroin and cigarettes in opioid-dependent outpatients.

Use of a time- and cost-efficient simulation procedure to assess reinforcement efficacy in humans was explored in the present study. Opioid-dependent outpatients completed questionnaires asking how many cigarettes or bags of heroin they would purchase across a range of prices. Reported consumption patterns conformed to a quantitative model that has been successful in accounting for data obtained in studies using real rather than hypothetical consequences, suggesting the self-report data may have been a valid proxy for observations of actual consumption patterns. Simulation procedures may thus be a useful supplement to traditional operant methods for the assessment of reinforcement efficacy in humans, particularly in situations where the use of operant methods is logistically difficult or ethically questionable. The relationship between behavioral-economic and traditional measures of reinforcement efficacy is also discussed.

Adult↗
PubMed1999

Abstinence and price effects on demand for cigarettes: a behavioral-economic analysis.

AIMS: To examine the separate and combined effects of cigarette pricing and cigarette abstinence on smoking. DESIGN: Within-subject design in which participants experienced all levels of price and abstinence conditions. SETTING: Laboratory conditions. PARTICIPANTS: Nine human cigarette smokers. INTERVENTION: Cigarette prices were manipulated across a 60-fold range (US$0.02-$1.20) in separate abstinent (5 + hours of non-smoking) and non-abstinent conditions. Participants earned money by pulling a response plunger (US$0.10 per 100 pulls) and could either keep the money or spend it on cigarette puffs. MEASUREMENTS: Total response output, cigarette consumption, price elasticity of demand and spending patterns. FINDINGS: Participants spent their earnings on cigarette puffs more quickly when abstinent than when they had smoked ad libitum before the session, and latency to spend money on puffs was a linear increasing function of price. Effects of abstinence on rates of smoking were a function of the price at which cigarette puffs could be purchased. At low prices participants smoked more puffs per session when abstinent, but this difference was negligible at high puff prices. Abstinence and non-abstinence effects were temporary, and tended to wane in the second 90 minutes of the sessions. During the first half of the sessions, demand for cigarettes was more inelastic during the abstinent condition than the non-abstinent condition, indicating relative insensitivity to price increases when abstinent. CONCLUSIONS: Behavioral-economic procedures and measures are sensitive to cigarette-abstinence manipulations and the laboratory methods employed here may prove beneficial in evaluating the probable effects of public-policy initiatives designed to reduce cigarette use.

Adult↗
PubMed1999

Behavioral and emotional problems among children of cocaine- and opiate-dependent parents.

OBJECTIVE: To test associations between parental drug abuse and children's problems, children of cocaine- and opiate-dependent parents were compared with demographically matched referred and nonreferred children. METHOD: Cocaine- and opiate-dependent parents in treatment completed the Child Behavior Checklist for 410 children (218 boys, 192 girls) from ages 2 through 18 years (mean = 7.9 years). Children of drug abusers (CDAs) were demographically matched to referred (RCs) and nonreferred children (NRCs). RESULTS: RCs scored lower than CDAs and NRCs on most competence scales, and higher than CDAs and NRCs on all problem scales. CDAs scored lower than NRCs on most competence scales, and higher than NRCs on Withdrawn, Thought Problems, Delinquent Behavior, Aggressive Behavior, Internalizing, Externalizing, and Total Problems. Group status also predicted clinical range scores on most competence and all problem scales. CONCLUSIONS: CDAs showed more internalizing and externalizing psychopathology relative to matched NRCs, but they showed significantly less psychopathology than shown by matched RCs. CDAs are an important group to target for preventive interventions.

Adolescent↗
PubMed1999

A comparison of measures of relative reinforcing efficacy and behavioral economics: cigarettes and money in smokers.

In this experiment, we compared behavioral economic measures and measures of the relative reinforcing efficacy of cigarettes and money between-participants. The experiment proceeded in two phases. In the first phase, money and cigarettes were available on separate progressive ratio (PR) schedules when they were solely available. The response requirement for the PR schedule increased across sessions, rather than within a session. In the second phase, money and cigarettes were made concurrently available at some of the response requirements employed during the PR schedule. Measures of (1) PR breakpoint, (2) peak response rate, (3) preference, (4) elasticity and (5) Pmax (the price at which the greatest amount of responding occurs) were compared within participant. Across the PR- and concurrent-schedule conditions, the three measures of reinforcing efficacy (breakpoint, response rate and preference) yielded an inconsistent assessment of the relative reinforcing efficacy of money and cigarettes. The reinforcer that resulted in greater peak response rates varied across subjects, while PR breakpoint was higher for cigarettes in all participants. Further, in concurrent schedules, preferences for cigarettes or money reversed across the response requirements. Behavioral economic analyses suggest that Pmax and elasticity are related to PR breakpoint, and that preference can be predicted from a comparison of the demand curves under single-schedule conditions. Implications for the concept of reinforcing efficacy are discussed.

Adult↗
PubMed1999

Therapeutic alliance and psychiatric severity as predictors of completion of treatment for opioid dependence.

OBJECTIVE: The role of patient characteristics and the strength of the therapeutic alliance in predicting completion of treatment by opioid-dependent patients was examined. METHODS: Information about patient characteristics and scores on subscales of the Addiction Severity Index (ASI) were obtained for 114 patients at intake to a buprenorphine treatment program lasting three to four months. The strength of the therapeutic alliance was assessed by the Helping Alliance Questionnaire (HAQ). Patients were classified as treatment completers or noncompleters, and logistical regression examined predictors of treatment completion. RESULTS: Only two variables significantly predicted treatment completion: severity of psychiatric symptoms and interaction between HAQ scores and psychiatric severity. Patients with fewer psychiatric symptoms were more likely to complete treatment. The strength of the therapeutic alliance was not related to treatment completion among patients with few psychiatric symptoms, and 62 percent of these patients completed treatment. In contrast, among patients with moderate to severe psychiatric problems, less than 25 percent with weak therapeutic alliances completed treatment, while more than 75 percent with strong therapeutic alliances completed treatment. CONCLUSIONS: The results underscore the importance of early identification of opioid-dependent patients with moderate to severe levels of psychopathology. In this patient subgroup, a strong therapeutic alliance may be an essential condition for successful treatment.

Adult↗
PubMed1999

Comparing single and cumulative dosing procedures in human triazolam discriminators.

This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination.

Adult↗
PubMed1999

Similar consumption and responding across single and multiple sources of drug.

Two experiments were conducted to assess whether total response output and total consumption would be similar when drugs are available from single and multiple sources of reinforcement, as predicted by behavioral economics. In Experiment 1, cigarette-deprived smokers were exposed to a concurrent-chains schedule in which equal fixed-ratio schedules served as the initial links, and different reinforcer magnitudes (i.e., number of cigarette puffs) were arranged across alternatives. After the session, obtained unit price was calculated and imposed in the next session when a different number of puffs was available according to a single fixed-ratio schedule. Thus, the unit price at which cigarette puffs could be earned was yoked within subjects across the single and concurrent-chains schedules. When plotted as a function of unit price, similar consumption and response rates were usually obtained across these schedules. Experiment 2 addressed a weakness of Experiment 1, namely, that responding was allocated exclusively to the larger reinforcer magnitude in concurrent-chains conditions, and therefore this schedule may have functioned as a single schedule. In Experiment 2, subjects were instructed to alternate responding between the two alternative schedules. Instructions produced approximately equal response allocation between the two alternatives. Again, similar consumption and response rates were observed across the single and instructed concurrent-chains schedules. These findings are discussed in the context of direct effects and behavioral economics perspectives of drug self-administration.

Adult↗
PubMed1999

Flumazenil discrimination by humans under a two-response and a novel-response procedure.

In this study we assessed the discriminative stimulus, self-reported, and performance effects of flumazenil in humans. The first group (n = 6) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.10, 0.32, 0.56, and 1.0 mg/70 kg) under a two-response drug discrimination procedure. The second group (n = 8) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.32, 0.56, and 1.0 mg/70 kg), midazolam (0.10, 0.56, and 1.0 mg/70 kg), and caffeine (75 mg/70 kg) under a novel-response drug discrimination procedure. In both groups, flumazenil was acquired and maintained as a discriminative stimulus. Flumazenil dose-dependently increased flumazenil-appropriate responding and ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. Under the novel-response procedure, midazolam produced dose-dependent increases in flumazenil-appropriate responding. However, midazolam produced 43 and 25% novel responding at the intermediate and highest test doses, respectively. Midazolam dose-dependently increased ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. The magnitude of effects on ratings of strength of drug effect and sedation were comparable after flumazenil and midazolam, but psychomotor performance effects were greater after midazolam than after flumazenil. Caffeine produced mostly saline-appropriate responding. The results indicate that flumazenil has agonist effects similar to those of midazolam; however, novel responding after midazolam, and the greater performance decrement after midazolam, suggest that flumazenil does not act as a traditional benzodiazepine agonist.

Adolescent↗