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Biomedical subjects

W K Bickel

Publications and source records attributed to W K Bickel.

At least 19 recordsLinked to original sources
PubMed1998

A comparison of subjective, psychomotor and physiological effects of a novel muscarinic analgesic, LY297802 tartrate, and oral morphine in occasional drug users.

This study compared the subjective, physiological and psychomotor effects of a novel muscarinic analgesic (LY297802) and oral morphine in healthy volunteers. Nine, non-dependent, occasional drug users participated in nine experimental sessions in which they received the following conditions: placebo, 0.1, 0.3, 0.56 and 1 mg of oral LY297802 and 10, 30, 56 and 100 mg of oral morphine. Subjective drug effects were assessed using the Visual Analog Scale (VAS), the Addiction Research Center Inventory (ARCI) and subjective and objective agonist and antagonist scales of the Adjective Rating Scale (ARS). These measures were collected 30 min before and every 30 min post drug administration for a 4-h period. Psychomotor performance was evaluated using the Digit Symbol Substitution Test (DSST) at these same time intervals. Physiological measures were collected continuously throughout the sessions. Oral morphine produced significant increases in some subjective effects scales, including elevations on the VAS, ARCI and ARS. In contrast, LY297802 did not engender changes different from placebo on any of these indices. Morphine produced significant dose-dependent effects in DSST performance, heart rate, blood oxygen saturation and pupil diameter. LY297802 significantly and dose dependently increased heart rate, mean arterial pressure and diastolic blood pressure. These results suggest that LY297802 does not induce subjective effects similar to morphine, but that it has some significant physiological effects.

Adult↗
PubMed1998

Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans.

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Adult↗
PubMed1998

Marijuana use and treatment outcome among opioid-dependent patients.

AIMS: Information concerning the association between marijuana use and opioid dependence and its treatment is needed to determine effective clinical guidelines for addressing marijuana use among opioid abusers. SETTING AND PARTICIPANTS: Marijuana use was assessed in 107 people enrolled in treatment for opioid dependence. DESIGN AND MEASUREMENT: Univariate comparisons of marijuana users and non-users and multivariate regression analyses were performed to examine associations between marijuana use and socio-demographic, psychosocial, medical and substance-use variables. The relationship between marijuana use and treatment outcome was also explored in a subset of this sample who received treatment that included buprenorphine detoxification and behavior therapy (N = 79). FINDINGS: Sixty-six per cent of participants were current marijuana users and almost all (94%) continued to use during treatment. Users were less likely to be married than non-users, and more likely to report financial difficulties, be involved in drug dealing and engage in sharing of needles (p < 0.05). A unique effect of marijuana use on drug dealing and sharing needles was retained after statistically controlling for the influence of heroin and alcohol use and other socio-demographic variables. No significant adverse relations were observed between marijuana use and treatment outcome. CONCLUSION: Pending a more comprehensive understanding of the function and consequences of marijuana use on psychosocial functioning, it appears that progress in treatment for opioid dependence can be made without mandating that patients abstain from marijuana use.

Adult↗
PubMed1998

Shortened time horizons and insensitivity to future consequences in heroin addicts.

AIMS: To investigate whether heroin addicts demonstrate shortened time horizons and decreased sensitivity to future consequences of their behavior compared to non-drug users. DESIGN SETTING AND PARTICIPANTS: Thirty-four heroin addicts enrolled in a buprenorphine treatment clinic and 59 non-drug-using controls completed a personality questionnaire and two laboratory tasks. MEASUREMENTS: The Stanford Time Perception Inventory (STPI) personality questionnaire assessed orientation to the future, and the Future Time Perspective (FTP) task elicited predictions of the timing and ordering of future events. The Bechara card task measured preferences for decks of cards that range in magnitude and probability of delayed and immediate rewards and punishers. FINDINGS: Heroin addicts scored significantly lower than controls on the STPI scale indicative of future orientation. In the FTP, heroin addicts were less likely to predict events far into the future and less likely to systematically organize events in the future. In the card task, heroin addicts were less likely to win money than controls. They were more likely to play from a deck that contained greater immediate gains but that resulted in large, delayed punishers and overall net losses. They also made fewer selections from a deck that provided an overall net gain via relatively low immediate rewards and frequent small punishments. CONCLUSIONS: Shortened time horizons and decreased sensitivity to delayed consequences may explain drug abusers' persistent use of drugs, despite the long-term negative consequences associated with drug use.

Adolescent↗
PubMed1998

A behavioral intervention for improving verbal behaviors of heroin addicts in a treatment clinic.

Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased.

Adult↗
PubMed1998

A 12-year study (1975-1986) of mortality in methadone-maintenance patients: selected demographic characteristics and drug-use patterns of AIDS and non-AIDS-related deaths.

This paper describes changes in demographic characteristics and drug use patterns of persons who died while enrolled in a New York City methadone-maintenance program during the years preceding and subsequent to the AIDS epidemic. Persons dying from AIDS were more likely to be younger, Hispanic, and male than those dying from other causes. Drug use increased during the 12-year study period, and the spread of the HIV infection among drug users may be reflected in an increased use of injectable drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Modeling drug dependence behaviors for animal and human studies.

Laboratory models are available to study drug reinforcement in animals and humans, but few are available to study other drug dependence phenomena, e.g., difficulty stopping or use despite harm. The present paper is a first attempt to illustrate the feasibility of developing such models for use in both nonhuman and human research and discusses their possible utility in research to understand and treat stimulant and other drug dependencies.

Animals↗
PubMed1997

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures.

Humans were trained to discriminate the benzodiazepine triazolam (0.32 mg/70 kg) from placebo under a two-response (drug vs. placebo) drug discrimination procedure. Dose-effect curves for several drugs were then determined in a crossover design using the two-response procedure and a 'novel-response procedure' that provided a novel-appropriate response for drugs unlike triazolam or placebo. Three subjects were tested with triazolam (0.1-0.32 mg/70 kg), the barbiturate secobarbital (56-177 mg/70 kg), and caffeine (320 and 560 mg/70 kg). Triazolam dose dependently increased triazolam-appropriate responding under both procedures and generally did not occasion novel-appropriate responding under the novel-response procedure. Secobarbital substituted for triazolam in the two-response procedure and dose-dependently increased novel-appropriate responding as well as occasioned some triazolam-appropriate responding in the novel-response procedure. Caffeine generally occasioned placebo-appropriate responding under the two-response procedure and a mix of novel- and placebo-appropriate responding under the novel-response procedure. Triazolam and secobarbital produced qualitatively similar self-reported drug effects. These results suggest that the novel-response procedure for human drug discrimination may enhance the pharmacological selectivity of triazolam- and placebo-appropriate responding.

Adult↗
PubMed1997

Effects of adding behavioral treatment to opioid detoxification with buprenorphine.

This trial assessed whether behavioral treatment improves outcome during a 26-week outpatient opioid detoxification. Thirty-nine opioid-dependent adults were assigned randomly to a buprenorphine dose-taper combined with either behavioral or standard treatment. Behavioral treatment included (a) a voucher incentive program for providing opioid-free urine samples and engaging in verifiable therapeutic activities and (b) the community reinforcement approach, a multicomponent behavioral treatment. Standard treatment included lifestyle counseling. Fifty-three percent of the patients receiving behavioral treatment completed treatment, versus 20% receiving standard treatment. The percentage of patients achieving 4, 8, 12, and 16 weeks of continuous opioid abstinence were 68, 47, 26, and 11 for the behavioral group and 55, 15, 5, and 0 for the standard group, respectively. Behavioral treatment improved outcomes during outpatient detoxification.

Adult↗
PubMed1997

Impulsive and self-control choices in opioid-dependent patients and non-drug-using control participants: drug and monetary rewards.

Delay discounting was investigated in opioid-dependent and non-drug-using control participants. The latter participants were matched to the former on age, gender, education, and IQ. Participants in both groups chose between hypothetical monetary rewards available either immediately or after a delay. Delayed rewards were $1,000, and the immediate-reward amount was adjusted until choices reflected indifference. This procedure was repeated at each of 7 delays (1 week to 25 years). Opioid-dependent participants were given a second series of choices between immediate and delayed heroin, using the same procedures (i.e., the amount of delayed heroin was that which could be purchased with $1,000). Opioid-dependent participants discounted delayed monetary rewards significantly more than did non-drug-using participants. Furthermore opioid-dependent participants discounted delayed heroin significantly more than delayed money.

Adolescent↗
PubMed1997

Modeling the effects of combined behavioral and pharmacological treatment on cigarette smoking: behavioral-economic analyses.

Effects of different response requirements, response-independent cigarette puffs, and an alternative nondrug reinforcer on cigarette smoking were assessed in 2 experiments. The response requirement to obtain 2 puffs on a cigarette was manipulated while various numbers of response-independent puffs were provided (0, 6, or 12 in Experiment 1; 0 or 12 in Experiment 2). In Experiment 2, effects of response-dependent money ($0.25) on smoking were assessed within subjects. Response-dependent puff consumption decreased as price increased and as the number of response-independent puffs increased. Concurrently available money also decreased response-dependent smoking. The largest decrease in smoking occurred when puffs were at the highest price and when response-independent puffs and response-dependent money were both concurrently available. Findings suggest that combined pharmacological and behavioral interventions produce the greatest reductions in smoking.

Adult↗
PubMed1997

Determination of buprenorphine in human plasma by gas chromatography-positive ion chemical ionization mass spectrometry and liquid chromatography-tandem mass spectrometry.

Buprenorphine is used for the management of pain and has been advocated for the treatment of opioid addiction. Therapeutic doses result in low plasma concentrations of buprenorphine. In order to assess the safety and efficacy of buprenorphine, sensitive analytical methods are needed. Until recently, gas chromatography-positive ion chemical ionization mass spectrometry (GC-PCI-MS) offered the most sensitive method to selectively quantitate buprenorphine. We have developed and validated a sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method for buprenorphine. The method is described and compared with a GC-PCI-MS method validated in this laboratory. One-milliliter aliquots of plasma are required for the LC-ESI-MS-MS method and 2-mL aliquots for the GC-PCI-MS method. Buprenorphine-d4 is used as internal standard for both methods. Derivatization with pentafluoropropionic acid anhydride is used for the GC-PCI-MS method, in which the derivatized protonated molecular ions after loss of water are monitored at m/z 596 and 600. For LC-ESI-MS-MS, the parent protonated molecule ions are monitored at m/z 468 and 472. A single-step extraction of basic plasma with n-butyl chloride provided recoveries of 70-87%. Although a limit of quantitation (LOQ) of 0.1 ng/mL could be established for LC-ESI-MS-MS, we could only achieve an LOQ of 0.5 ng/mL with the GC-PCI-MS assay. The GC-PCI-MS method has a linear range of 0.5 to 40 ng/mL (mean r2 = 0.998, n = 7). For quality control samples at 1.0, 2.5, and 12.5 ng/mL, the intra- and interassay coefficients of variation (CV) did not exceed 14%, and percent of targets were within 16%. The LC-ESI-MS-MS method had a linear range of 0.1 to 10 ng/mL (mean r2 = 0.999, n = 7). For quality control samples at 0.25, 2.5 and 7.5 ng/mL, the intra- and interassay CVs did not exceed 4%, and percent of targets were within 12%. Stability studies demonstrated buprenorphine was stable for up to 24 h, 125 days, and 55 days when stored at room temperature, 4 degrees C, and -20 degrees C, respectively. The utility of the lower LOQ was demonstrated in 40 plasma samples collected up to 96 h after a sublingual dose of buprenorphine; 10 were quantitatable using GC-PCI-MS and 38 using LC-ESI-MS-MS.

Administration, Sublingual↗
PubMed1997

Functional antagonism of the caffeine-discriminative stimulus by triazolam in humans.

Six healthy male volunteers (aged 21-31 yr) were trained to discriminate between the methylxanthine caffeine (320 mg/70 kg, p.o.; e.g. drug A) and placebo (drug B). Then dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), alone and in combination with the caffeine training dose (n = 6), buspirone (1.0-32.0 mg/70 kg), alone and in combination with the caffeine training dose (n = 4), and caffeine (56-560 mg/70 kg), alone and in combination with a selected dose of triazolam (n = 5). Triazolam blocked the discriminative effects of the caffeine training dose in a dose-related manner in five out of six subjects; whereas buspirone did so in only one out of four subjects. Different doses of caffeine alone generally produced dose-related increases in caffeine-appropriate responding; when administered concomitantly with triazolam, the caffeine dose-effect curve shifted significantly to the right. Triazolam and caffeine, but not buspirone and caffeine, generally produced significant interactions on several self-report and psychomotor performance measures. These results indicate that, at the doses tested, the caffeine discriminative stimulus can be blocked, at least partly by triazolam, but not by buspirone, which is consistent with the pharmacological actions of these compounds.

Adult↗
PubMed1996

Alcohol pretreatment increases preference for cocaine over monetary reinforcement.

Non-dependent cocaine users participated in a two-phase experiment conducted under controlled laboratory conditions. During phase 1, subjects sampled intranasal cocaine (100 mg) and placebo (96 mg lactose + 4 mg cocaine) in separate sessions and under double-blind conditions. Sampling sessions were followed by a single choice session in which subjects made a maximum of ten choices between 10 mg unit doses of cocaine or placebo. Only subjects who reliably (> or = 70%) chose cocaine over placebo in phase 1 participated in phase 2. During phase 2, subjects participated in a series of nine experimental sessions conducted on different days in which they were pretreated with varying doses of alcohol (placebo, 0.5, and 1.0 g/kg) and made a maximum of ten choices between 10 mg unit doses of cocaine and an alternative reinforcer (i.e., varying amounts of money). Visual-analog ratings of drug effects and cardiac function were monitored across all experimental sessions. Cocaine was reliably chosen over placebo by the majority (9 of 11) of subjects during phase 1, demonstrating that the drug functioned as a reinforcer. During phase 2, alcohol pretreatment significantly increased choice of cocaine over the alternative reinforcer, while increasing monetary value decreased cocaine choice. Ratings on some visual-analog scales (e.g., good effects) paralleled cocaine choice, with alcohol pretreatment increasing ratings and greater monetary value decreasing them. Cardiac output increased above baseline levels across all alcohol and monetary conditions, but maximal effects were observed during sessions involving pretreatment with the active alcohol doses. Overall, these results demonstrate (a) that alcohol can increase preference for cocaine over alternative reinforcers and thereby may thwart efforts to reduce or abstain from cocaine use, (b) that availability of an alternative, non-drug reinforcer can effectively decrease preference for cocaine, and (c) that combined use of alcohol and cocaine increases cardiac risk compared to use of cocaine alone.

Adult↗
PubMed1996

A comparison of cocaine-dependent cigarette smokers and non-smokers on demographic, drug use and other characteristics.

Cigarette smoking (n = 156) and non-smoking (n = 43) individuals seeking out-patient treatment for cocaine-dependence were compared on demographic, drug use and other variables. Smokers were younger, less educated, earned less money, began cocaine use at an earlier age, used cocaine more frequently, were more likely to inject or smoke cocaine, were more likely to report legal troubles and having harmed someone physically as consequences of their cocaine use, and had more severe employment and legal problems than non-smokers as measured by the Addiction Severity Index. Smoking remained a significant predictor of more frequent cocaine use, using more grams of cocaine per week and using cocaine via an injection or smoking route even after adjusting for demographic differences between smokers and non-smokers via regression analyses. Smoking status was not significantly related to treatment outcome. Overall, these results indicate that cocaine-dependent smokers represent a more high-risk group than non-smokers. This relationship between smoking, cocaine use, and associated problems merits further investigation.

Adult↗
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↗
PubMed1995

Implications of behavioral pharmacology research for applied behavior analyses: JEAB's special issue celebrating the contributions of Joseph V. Brady (March 1994).

We review four articles from JEAB's March 1994 issue celebrating the contributions of Joseph V. Brady. These articles have implications for studying private events and for studying multiple operants. We suggest that regularly including self-reports about private events in behavioral pharmacological research has resulted in an accumulated knowledge that has facilitated examination of interesting relations among self-reports, environmental factors, and other observable behaviors. Methodological lessons that behavioral pharmacologists have learned regarding the study of multiple operants are also relayed. We provide examples of how these lessons could be useful to applied behavior analysts studying nonpharmacological issues.

Adult↗