Methamphetamine administration dose effects on sexual desire, sexual decision making, and delay discounting.

Correlational evidence has linked methamphetamine use and HIV sexual risk behavior, but the direct effects of methamphetamine on sexual desire and sexual decision making in humans have not been tested. This study was designed to test the effect of methamphetamine administration on sexual desire and hypothetical condom-use decisions as measured by the Sexual Delay Discounting Task. Recreational stimulant users (n = 19) participated in this within-subject, placebo-controlled study comparing the effects of 0 mg, 20 mg, and 40 mg of oral methamphetamine. Compared to placebo, methamphetamine caused dose-related and time-related increases in a single-item sexual desire rating and some standard stimulant abuse liability ratings, as well as dose-related increases in the Sexual Arousal and Desire Inventory (SADI; a multidimensional scale capturing positive and negative aspects of desire/arousal). However, methamphetamine caused no significant mean differences in likelihood of condom use within the Sexual Delay Discounting Task or the Monetary Discounting Task. SADI scores were negatively correlated with change from placebo in condom use likelihood in the Sexual Delay Discounting Task for some partner conditions (i.e., decreased reported likelihood of condom use in participants who experienced increased desire/arousal and vice versa). These mixed results may be consistent with methamphetamine's role as both a treatment for attention-deficit/hyperactivity disorder and as a drug of abuse associated with increased delay discounting, and they suggest that methamphetamine's effects on discounting may be modulated by the reinforcing properties of what is being discounted. Delay discounting may be an understudied element of risky sexual decision making, particularly among individuals who use methamphetamine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Randomized controlled trial of d-cycloserine in cocaine dependence: Effects on contingency management and cue-induced cocaine craving in a naturalistic setting.

Cocaine dependence constitutes a significant public health concern. This randomized, double-blind, placebo-controlled trial tested a novel approach to reducing cocaine use among cocaine-dependent individuals with d-cycloserine, a drug known to enhance learning and some learning-based therapies. Urine samples and cocaine craving were assessed across three phases: induction (Weeks 1-2), treatment (Weeks 3-5; urinalysis-based contingency management plus exposure therapy), and posttreatment (Weeks 6-7). During the treatment phase, either 50 mg of d-cycloserine or placebo was administered after delivery of urinalysis feedback with potential monetary reward and before exposure therapy sessions in naturalistic contexts individually associated with cocaine use. d-cycloserine significantly improved learning on an operant laboratory task. Contingency management significantly reduced cocaine use and craving. d-cycloserine did not significantly affect cocaine use or craving in the treatment phase. Craving significantly increased for the d-cycloserine group during the post treatment phase. Therefore, although the study showed that d-cycloserine was capable of improving learning, enhancement of learning-based therapy was not observed. Moreover, no differences in behavioral measures of cocaine demand (cocaine purchasing task) or monetary or sexual delay discounting were observed across phases or between groups in any phase. These results are somewhat consistent with previous findings suggesting that d-cycloserine administration increases cocaine craving, although they differ from other findings showing that d-cycloserine administration reduces alcohol or nicotine cravings. Methodological variables (e.g., guided vs. unguided exposure therapy sessions, length of extinction exposure) likely play a role in dissimilar findings observed across studies. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

INTRODUCTION: Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. METHODS: Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. RESULTS: PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. CONCLUSIONS: Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use.

Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population.

Demand curves for hypothetical cocaine in cocaine-dependent individuals.

RATIONALE: Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. OBJECTIVES: This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. METHODS: Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. RESULTS: Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. CONCLUSIONS: Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

Test-retest reliability and gender differences in the sexual discounting task among cocaine-dependent individuals.

The Sexual Discounting Task uses the delay discounting framework to examine sexual HIV risk behavior. Previous research showed task performance to be significantly correlated with self-reported HIV risk behavior in cocaine dependence. Test-retest reliability and gender differences had remained unexamined. The present study examined the test-retest reliability of the Sexual Discounting Task. Cocaine-dependent individuals (18 men, 13 women) completed the task in two laboratory visits ∼7 days apart. Participants selected photographs of individuals with whom they were willing to have casual sex. Among these, participants identified the individual most (and least) likely to have a sexually transmitted infection (STI), and the individual with whom he or she most (and least) wanted to have sex. In reference to these individuals, participants rated their likelihood of having unprotected sex versus waiting to have sex with a condom, at various delays. A money delay discounting task was also completed at the first visit. Significant differences in discounting among partner conditions were shown. Differential stability was demonstrated by significant, positive correlations between test and retest for all four partner conditions. Absolute stability was demonstrated by statistical equivalence tests between test and retest, and also supported by a lack of significant differences between test and retest. Men generally discounted significantly more than women for sexual outcomes but not money. Results suggest the Sexual Discounting Task to be a reliable measure in cocaine-dependent individuals, which supports its use as a repeated measure in clinical research, for example, studies examining acute drug effects on sexual risk and the effects of addiction treatment and HIV prevention interventions on sexual risk.

Effects of prenatal stress on lever-press acquisition with delayed reinforcement in male and female rats.

The prenatally stressed (PS) rat shows enhanced conditioned fear and increased behavioral inhibition in response to footshock compared to control (CON) rats. It is unclear whether this facilitated learning will occur only with aversive stimulation, or if it will also be observed in the context of positive reinforcement. There are limited and inconsistent data regarding sex differences and the impact of prenatal stress on learning. The present study was designed to examine lever-press acquisition with a 10-s delay to food reinforcement in male and female PS and CON rats. Overall, twice as many PS male rats acquired the lever-press response than the PS female rats, CON male rats, and CON female rats. PS male rats also earned significantly more reinforcers and responded on the operative lever at a significantly greater rate than the other three rat groups. These findings suggest that PS rats exhibit altered learning with a task involving positive reinforcement, and this effect of PS is sex specific for male rats.

The Sexual Discounting Task: HIV risk behavior and the discounting of delayed sexual rewards in cocaine dependence.

BACKGROUND: Cocaine dependence is associated with high rates of sexual risk behavior and HIV infection. However, little is known about the responsible mechanism(s). METHODS: Cocaine-dependent individuals (N=62) completed a novel Sexual Discounting Task assessing decisions between immediate unprotected sex and delayed sex with a condom across four hypothetical partners: most (and least) likely to have a sexually transmitted infection (STI), and most (and least) sexually desirable; a real rewards money delay-discounting task, and self-reported sexual risk behavior using the HIV Risk-Taking Behavior Scale (HRBS). RESULTS: Sexual Discounting Task results were largely systematic and showed a strong effect of delay in decreasing condom use. Sexual discounting (preference for immediate unprotected sex) was significantly greater when making responses for partners judged least (compared to most) likely to have an STI, and for partners judged most (compared to least) desirable. Differences in sexual discounting were significant after controlling for differences in condom use (with no delay) between conditions. Greater discounting in 3 of the 4 Sexual Discounting Task conditions, but not in the money discounting task, was associated with greater self-reported sexual risk behavior as measured by the HRBS. CONCLUSIONS: Results suggest that delay is a critical variable strongly affecting HIV sexual risk behavior, and that the Sexual Discounting Task provides a clinically sensitive measure of this phenomenon that may address a variety of questions about HIV risk in future research. The wealth of behavioral and neurobiological data on delay discounting should be brought to bear on HIV education and prevention.

Discriminative-stimulus and time-course effects of kava-kava (Piper methysticum) in rats.

Kava is a widely available and used herbal medicine that is not regulated in many countries. There are many questions concerning kava's stimulus properties, potential for therapeutic use, and potential for abuse. Although there is evidence that kava may possess some anxiolytic properties, kava's mechanism of action and the extent to which it may serve as an alternative to pharmaceutical anxiolytics are not fully known. The current study was designed to evaluate whether kava shares discriminative-stimulus properties with the anxiolytic chlordiazepoxide (CDP). Effects of different doses of kava extract were evaluated in two groups of rats trained to discriminate either a high or low training dose of CDP (i.p.). In order to assess time-course effects, two tests were conducted/session at 60 (Test One) and 90 (Test Two) min following oral administration of kava, CDP, or d-amphetamine. Dose-dependent substitution of CDP was found in both training groups in both tests. Kava (560 mg/kg, p.o.) occasioned responding indicative of partial substitution in both groups during Test One and only the low-dose group during Test Two. Partial substitution of kava extract for CDP suggests that the herbal compound may share a mechanism of action similar to CDP, but is less potent.