The phenotype of recovery VIII: Association among delay discounting, recovery capital, and length of abstinence among individuals in recovery from substance use disorders.

INTRODUCTION: Research defines recovery capital as the amount of tangible and intangible resources (e.g., human/personal, physical, social, and cultural) available to initiate and sustain recovery from substance use disorders (SUDs). An individual's amount of recovery capital is dynamic over time and influenced by a number of factors such as baseline amount at initiation of recovery/treatment, length of abstinence, access/availability of resources, and individual factors such as the decision to utilize available resources. Research has been proposed delay discounting (DD), which reflects an individual's relative preference for immediate versus delayed rewards, as a candidate behavioral marker for SUDs but has not yet examined it in the context of recovery capital, and DD may be an important aspect of human capital. Thus, the aim of the current study was to examine associations among recovery capital, DD, and length of abstinence. METHODS: The study included in its analysis data from 111 individuals in recovery from SUDs from the International Quit and Recovery Registry, an ongoing data collection program used to further scientific understanding of recovery. The study assessed recovery capital using the Assessment of Recovery Capital (ARC) and assessed discounting rates using an adjusting-delay task. The study team performed univariate linear regression to examine the relationship between total ARC score and demographic variables, length of abstinence, and DD. The research team performed a mediation analysis to understand the role of length of abstinence in mediating the relationship between DD and ARC score. RESULTS: Total ARC score was significantly negatively associated with DD and positively associated with length of abstinence, even after adjusting for covariates. Mediation analysis indicated that length of abstinence significantly partially mediated the relationship between DD and ARC score. CONCLUSION: These findings support the characterization of DD as an important aspect of human capital and a candidate behavioral marker for SUDs. Future research may wish to investigate whether interventions designed to increase the value of future rewards also increase recovery capital.

Delay discounting and utility for money or weight loss.

OBJECTIVE: Obesity is related to a bias towards smaller immediate over larger delayed rewards. This bias is typically examined by studying single commodity discounting. However, weight loss often involves choices among multiple commodities. To our knowledge, no research has examined delay discounting of delayed weight loss compared with other commodities. METHODS: We examined single commodity discounting of money and cross commodity discounting of money and weight loss in a sample of 84 adults with obesity or overweight statuses interested in weight loss. The exchange rate between money and weight loss was calculated, and participants completed two delay discounting tasks: money now versus money later and money now versus weight loss later. RESULTS: Participants discounted weight loss more than money (p < 0.001). When participants were divided into those who preferred weight loss (n = 61) versus money (n = 23), those who preferred money over weight loss discounted weight loss even more than individuals that preferred weight loss (p = 0.003). CONCLUSIONS: Greater discounting of weight loss for those who preferred money suggest that idiosyncratic preferences are related to multiple commodity discounting, and greater discounting of weight loss across all participants provide insight on important challenges for weight control.

Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing.

Understanding the abuse liability of novel drugs is critical to understanding the risk these new compounds pose to society. Behavioral economics, the integration of psychology and economics, can be used to predict abuse liability of novel substances. Here, we describe the behavioral economic concept of reinforcer pathology and how it may predict the use of novel drugs in existing drug-users and initiation of use in the drug-naive.

Does impulsivity change rate dependently following stimulant administration? A translational selective review and re-analysis.

RATIONALE: Rate dependence refers to an orderly relationship between a baseline measure of behavior and the change in that behavior following an intervention. The most frequently observed rate-dependent effect is an inverse relationship between the baseline rate of behavior and response rates following an intervention. A previous report of rate dependence in delay discounting suggests that the discounting of delayed reinforcers, and perhaps, other impulsivity measures, may change rate dependently following acute and chronic administration of potentially therapeutic medications in both preclinical and clinical studies. OBJECTIVE: The aim of the current paper was to review the effects of stimulants on delay discounting and other impulsivity tasks. METHODS: All studies identified from the literature were required to include (1) an objective measure of impulsivity; (2) administration of amphetamine, methylphenidate, or modafinil; (3) presentation of a pre- and postdrug administration impulsivity measure; and (4) the report of individual drug effects or results in groups split by baseline or vehicle impulsivity. Twenty-five research reports were then reanalyzed for evidence consistent with rate dependence. RESULTS: Of the total possible instances, 67 % produced results consistent with rate dependence. Specifically, 72, 45, and 80 % of the data sets were consistent with rate dependence following amphetamine, methylphenidate, and modafinil administration, respectively. CONCLUSIONS: These results suggest that rate dependence is a more robust phenomenon than reported in the literature. Impulsivity studies should consider this quantitative signature as a process to determine the effects of variables and as a potential prognostic tool to evaluate the effectiveness of future interventions.

Longitudinal Associations Among Religiousness, Delay Discounting, and Substance Use Initiation in Early Adolescence.

Prior research indicates that religiousness is related negatively to adolescent health risk behaviors, yet how such protective effects operate is not well understood. This study examined the longitudinal associations among organizational and personal religiousness, delay discounting, and substance use initiation (alcohol, cigarette, and marijuana use). The sample comprised 106 early adolescents (10-13 years of age, 52% female) who were not using substances at Time 1. Path analyses suggested that high levels of personal religiousness at Time 1 were related to low levels of substance use at Time 2 (2.4 years later), mediated by low levels of delay discounting. Delay discounting appears to be an important contributor to the protective effect of religiousness on the development of substance use among adolescents.

A Competing Neurobehavioral Decision Systems model of SES-related health and behavioral disparities.

We propose that executive dysfunction is an important component relating to the socio-economic status gradient of select health behaviors. We review and find evidence supporting an SES gradient associated with (1) negative health behaviors (e.g., obesity, excessive use of alcohol, tobacco and other substances), and (2) executive dysfunction. Moreover, the evidence supports that stress and insufficient cognitive resources contribute to executive dysfunction and that executive dysfunction is evident among individuals who smoke cigarettes, are obese, abuse alcohol, and use illicit drugs. Collectively these data support the dual system model of cognitive control, referred to here as the Competing Neurobehavioral Decision Systems hypothesis. The implications of these relationships for intervention and social justice considerations are discussed.

Altruism in time: social temporal discounting differentiates smokers from problem drinkers.

RATIONALE: Recent studies on reinforcer valuation in social situations have informed research on mental illness. Social temporal discounting may be a way to examine effects of social context on the devaluation of delayed reinforcers. In prior research with non-drug-using groups, we demonstrated that individuals discount delayed rewards less rapidly (i.e., value the future more) for a group of which they are a member than they do for themselves alone. OBJECTIVES: The current study examined how cigarette smoking and level of alcohol use relate to rates of delay and social temporal discounting. METHODS: In this study, we used crowd-sourcing technology to contact a large number of individuals (N = 796). Some of these individuals were hazardous-to-harmful drinkers (n = 269), whereas others were non-problem drinkers (n = 523); some were smokers (n = 182), whereas others were nonsmokers (n = 614). Delay discounting questionnaires for individual rewards (me now, me later) and for group rewards (we now, we later; me now, we later) were used to measure individuals' discounting rates across various social contexts. RESULTS: Our analyses found that smokers discounted delayed rewards more rapidly than controls under all conditions. However, hazardous-to-harmful drinkers discounted delayed rewards significantly more rapidly than the non-problem drinkers under the individual condition, but not under the social conditions. CONCLUSIONS: This finding suggests that the use of different abused drugs may be associated with excessive discounting in the individual condition and has selective effects when discounting for a group in the social conditions.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Quantitative analysis of reproducible changes in high-voltage electrophotography.

OBJECTIVES: The existence of electromagnetic fields not generated by neuronal action or muscle stimulation remains controversial especially because they are difficulty to detect. We attempted to investigate the existence of electromagnetic fields associated with biologic systems using new image analysis techniques to analyze high-voltage electrophotography. DESIGN/SUBJECTS: Five energy practitioners (three males and two females) and five control subjects (four males and one female) participated in the study. Each practitioner had studied a formal training curriculum and was a professional energy practitioner. Images representing attempts of both energy practitioners and controls to elicit a change in electromagnetic emissions were captured by electrophotographic means. A statistical analysis on the comparison of "ON" vs. "OFF" states for the controls and practitioners in the study was made via digital representation of analogue images. RESULTS: Our interest was threefold: (1) to determine whether corona discharge patterns could be obtained and photographed and be reproducible; (2) to quantify some of the qualitative properties of the coronas; and (3) to determine if individuals can alter, at will, their electrophotographic images. We found a correlation between a change in the electromagnetic emissions for the body and the conscious desire of an energy practitioner to change this state. Analyses of individual finger coronas demonstrate statistically significant differences as analyzed by overall color changes and via analysis of individual sections of the various colors dominating the field. Control subjects were unable to produce statistically significant changes that were reproducible. Physiologic processes, such as changes in skin resistance, sweating, and surface blood constriction, have been suggested as an explanation of the colors and patterns that appear on the film in previous studies, but were not observed in this investigation. CONCLUSIONS: After controlling for the above variables and identifying reproducible and statistically significant changes, we believe the images created in our study represent the interaction of biologically generated electromagnetic fields interacting with the corona discharge created by the electrophotographic device.

Two-beam Coupling Modules for Photorefractive Optical Circuits.

Modules that perform photorefractive two-beam coupling operations have been built, characterized, and tested. These portable modules, interconnected by fiber optics, dispense with the need for repeated alignment and greatly facilitate the prototyping of complex signal- or image-processing photorefractive circuits. To evaluate the performance of the modules in a photorefractive circuit, we interconnected them in the feature extractor configuration: a ring configuration composed of two modules that selects the strongest signal within the signals presented on its input. With two signals at the input, an output contrast ratio of 45.4 dB is obtained for an input contrast ratio of 5 dB.

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.

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.