Daily temporal patterns of heroin and cocaine use and craving: Relationship with business hours regardless of actual employment status

Real-time monitoring of behavior using Ecological Momentary Assessment (EMA) has provided detailed data about daily temporal patterns of craving and use in cigarette smokers. We have collected similar data from a sample of cocaine and heroin users. Here we analyzed it in the context of its relationship with a societal construct of daily temporal organization: 9-to-5 business hours. In a 28-week prospective study, 112 methadone-maintained polydrug-abusing individuals initiated an electronic-diary entry and provided data each time they used cocaine, heroin, or both during weeks 4 to 28. EMA data were collected for 10,781 person-days and included: 663 cocaine-craving events, 710 cocaine-use events, 288 heroin-craving events, 66 heroin-use events, 630 craving-both-drugs events, and 282 use-of-both-drugs events. At baseline, 34% of the participants reported full-time employment in the preceding 3-year period. Most participants' current employment status fluctuated throughout the study. In a generalized linear mixed model (SAS Proc Glimmix), cocaine use varied by time of day relative to business hours (p < 0.0001) and there was a significant interaction between Day of the Week and Time Relative to Business Hours (p < 0.002) regardless of current work status. Cocaine craving also varied by time of day relative to business hours (p < 0.0001), however, there was no significant interaction between Day of the Week and Time Relative to Business Hours (p = .57). Heroin craving and use were mostly reported during business hours, but data were sparse. Cocaine craving is most frequent during business hours while cocaine use is more frequent after business hours. Cocaine use during business hours, but not craving, seems suppressed on most weekdays, but not weekends, suggesting that societal conventions reflected in business hours influence drug-use patterns even in individuals whose daily schedules are not necessarily dictated by employment during conventional business hours.     

Tobacco,cocaine, and heroin: Craving and use during daily life

Background

Relationships among tobacco smoking, tobacco craving, and other drug use and craving may have treatment implications in polydrug-dependent individuals.

Methods

We conducted the first ecological momentary assessment (EMA) study to investigate how smoking is related to other drug use and craving during daily life. For up to 20 weeks, 106 methadone-maintained outpatients carried PalmPilots (PDAs). They reported their craving, mood, behaviors, environment, and cigarette-smoking status in 2 to 5 random-prompt entries/day and initiated PDA entries when they used cocaine or heroin or had a discrete episode of craving for cocaine or heroin.

Results

Smoking frequency increased linearly with random-prompt ratings of tobacco craving, cocaine craving, and craving for both cocaine and heroin. Smoking frequency was greater during discrete episodes of cocaine use and craving than during random-prompt reports of low craving for cocaine. This pattern was also significant for dual cocaine and heroin use and craving. Smoking and tobacco craving were each considerably reduced during periods of urine-verified abstinence from cocaine, and there was a (nonsignificant) tendency for morning smoking to be especially reduced during those periods.

Conclusions

This EMA study confirms that smoking and tobacco craving are strongly associated with the use of and craving for cocaine and heroin. Together with prior findings, our data suggest that tobacco and cocaine may each increase craving for (and likelihood of continued use of) themselves and each other. Treatment for tobacco dependence should probably be offered concurrently with (rather than only after) initiation of treatment for other substance-use disorders.     

Cocaine-induced cocaine craving

In nine experienced users of cocaine, we examined the urge to use cocaine or other drugs following a 40 mg dose of intravenous (IV) cocaine with and without oral pretreatment with 2.5 mg bromocriptine. The urge to use cocaine was assessed with a questionnaire constructed to assess both wanting and craving for cocaine or other drugs. Fifteen minutes after the administration of cocaine (but not after placebo), subjects' ratings for both drug wanting and drug craving were significantly increased. Our results provide a laboratory demonstration of cocaine-induced increases in the urge to use drugs in humans. The findings, stressing the role of internal stimuli associated with drug administration, suggest the possibility of distinguishing among related, but perhaps distinct, components of the fluctuating levels of motivation to reuse drugs.     

Predicting craving among cocaine users

INTRODUCTION: Craving for cocaine seems to play an important role in the continued use of and dependence on the substance. AIMS: to describe characteristics of the craving phenomenon in a sample of cocaine users and to identify those that could predict the appearance of the phenomenon. METHOD: 205 cocaine users attending an outpatient clinic were interviewed to assess patterns of drug consumption and characteristics of craving for the drug. FINDINGS: Subjects were mostly young (24.8+/-12.8 years) and male (86.2%). One hundred and two subjects (49.8%) were addicted to cocaine and the remainders (50.2%) were non-addicted occasional cocaine users. The majority of subjects (60.5%) reported having had craving episodes during the previous week. Frequency of cocaine use during the previous month correlated with the number of reported craving fits (r=0.425; p<0.001) and with the duration of the craving fits (r=0.351; p<0.001). Users of crack reported more craving episodes than did the users of snorted cocaine (p<0.001) and the frequency of craving fits was inversely proportional to the duration of abstinence from the drug (r=-0.405; p<0.001). CONCLUSION: Both the method of drug consumption and the abstinence period elapsed since previous drug intake were identified as predictive parameters of craving.     

Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour

RATIONALE AND OBJECTIVES: To review the literature on the use of second-order schedules of drug reinforcement in the context of experimental investigations of the neural and pharmacological mechanisms underlying addictive behaviour in general and drug-seeking behaviour in particular. METHODS: Second-order schedules of drug reinforcement are described in which responding is maintained not only by the self-administered drug, but also by contingent presentation of drug-paired stimuli that serve as conditioned reinforcers of instrumental behaviour. RESULTS: The behaviour of rats and monkeys responding under second-order schedules is discussed in relation to self-administered drug dose and the importance of drug-associated cues in maintaining responding for cocaine, morphine or heroin. Drug-seeking behaviour during the period before drug is self-administered is described and compared with drug-seeking behaviour derived from other procedures. In addition, results are summarised that demonstrate the differential involvement of the amygdala and prefrontal cortex in the acquisition of cue-controlled cocaine- and heroin-seeking behaviour, as well as the effects of drugs interacting with D3 dopamine, NMDA and AMPA receptors on drug-seeking behaviour and dopaminergic correlates of drug-paired stimuli presented non-contingently and during responding for cocaine under a second-order schedule. CONCLUSIONS: We argue that the first, drug-free interval (or other period) of responding under a second-order schedule of reinforcement has particular utility in that it provides a measure of drug-seeking behaviour and reinforcing efficacy that are not affected by the pharmacological effects of recently administered drug. It also provides a means of investigating the role of drug-paired stimuli in drug-seeking behaviour, including its behavioural, neural and neurochemical basis.     

Psychological stress, drug-related cues and cocaine craving

RATIONALE: While several environmental situations may produce cocaine craving, there is little research on whether patterns of drug cue reactivity are similar across different environmental situations. OBJECTIVE: This study examined whether two different environmental situations, psychological stress and drug cues, produce similar or varying patterns of cue reactivity in 20 cocaine dependent individuals. METHODS: All subjects participated in a single laboratory session and were exposed to stress, drug cues and neutral-relaxing imagery conditions. Cocaine and alcohol craving, emotion state ratings, subjective anxiety, heart rate and salivary cortisol measures were assessed. RESULTS: Significant increases in cocaine and alcohol craving were observed with stress and drug cues imagery but not with neutral-relaxing imagery. In addition, stress and drug cues situations produced similar increases in subjective anxiety, heart rate and salivary cortisol levels. Significant increases in negative emotion ratings and decreases in positive emotion ratings were found for stress and drug cues conditions as compared to the neutral condition. CONCLUSIONS: The findings indicate that a similar and comparable pattern of cue reactivity is induced by stress and drug cue manipulations. Furthermore, the comparable increases in subjective anxiety and negative affect observed with stress-induced and drug cue-induced craving provides support for the negative reinforcement model of drug craving and relapse. The negative affectivity co-occurring with the craving state appears to be an important target in the development of new treatments for cocaine dependence.     

The effect of baseline cocaine use on treatment outcomes for heroin dependence over 24 months: findings from the Australian Treatment Outcome Study

AIMS: The aim of this study was to determine the effects of baseline cocaine use on treatment outcomes for heroin dependence over a 24-month period. DESIGN: A longitudinal cohort (24 months) study was carried out. Interviews were conducted at baseline, 3, 12, and 24 months. SETTING: The study setting was Sydney, Australia. PARTICIPANTS: Six hundred fifteen heroin users were recruited for the Australian Treatment Outcome Study. FINDINGS: Cocaine use was common at baseline (40%) but decreased significantly over the study period. Even after taking into account age, sex, treatment variables, current heroin use, and baseline polydrug use, baseline cocaine use remained a significant predictor of poorer outcomes across a range of areas. Baseline cocaine users were more likely to report heroin use, unemployment, needle sharing, criminal activity, and incarceration over the 24-month study period. CONCLUSIONS: Cocaine consumption among heroin users has repercussions across a range of areas that persist far beyond the actual period of use. Consequently, treatment providers should regard cocaine use among clients as an important marker for individuals who are at risk of poorer treatment outcome.     

Stress-induced craving and stress response in cocaine dependent individuals

Two laboratory studies were conducted to examine the effects of acute psychological stress on craving and stress reactivity in cocaine abusers. In the first preliminary study, we examined the effects of a speech stressor task and a personalized stress imagery task on self-reported craving and emotional state in ten cocaine abusers. Both stressors led to significant decreases in neutral and joy states, and significant increases in fear ratings as compared to baseline ratings. In addition, the stress imagery condition led to significant increases in cocaine craving and sadness and anger ratings, as compared to baseline. Thus, the personalized stress imagery task appeared to be more effective than the speech stress task in inducing craving in the laboratory. The second study examined the effects of stress imagery as compared to neutral imagery on cocaine craving, subjective anxiety and physiological responses in a second group of ten cocaine abusers. The stress imagery task once again produced significant increases in cocaine craving along with increases in heart rate, salivary cortisol and subjective anxiety ratings. These data are the first to document that acute psychological stress consistently increases craving for cocaine in cocaine abusers. The studies also provide a promising method for examining the association between stress and drug craving in the laboratory. Received: 9 March 1998/Final version: 14 September 1998     

Marriage and relationship closeness as predictors of cocaine and heroin use

Marriage has been cited as a protective factor against drug use, but the relationship between marriage and drug use has not been explored longitudinally during addiction treatment. The current study assessed individual trajectories of substance use during treatment as a function of marital status and perceived closeness of the marital relationship. A parallel-process growth model was used to (1) estimate the rate of change in percentage of cocaine-positive and heroin-positive urine samples, and (2) examine the relationship between marital status and drug use trajectories over 35 weeks, during and after treatment. Percent days of use for both drugs were lowest for married participants across all time points. Among married participants, reporting a close relationship with one's partner predicted less cocaine and heroin use. These findings suggest that being married and having a close relationship with one's spouse are associated with better outcomes over time. The causal nature of the association is suggested by previous research that has demonstrated the effectiveness of couples therapy as an adjunct to methadone maintenance.     

A preliminary report on the use of virtual reality technology to elicit craving and cue reactivity in cocaine dependent individuals

In the present feasibility study, we developed a 3-dimensional virtual "crack" cocaine environment and evaluated the environment's ability to elicit subjective craving and cue reactivity (i.e., subjective emotional responding, heart rate and skin conductance) in 11 crack cocaine dependent individuals. Each of the seven 3-D crack cocaine scenes in the cocaine environment depicted actors engaging in a range of using-related behaviors (i.e., smoking crack) whereas the neutral environment contained scenes depicted 3-D aquariums with active aquatic life (baseline measures were obtained following immersion in the neutral environment). Results indicated that craving was significantly elevated during the cocaine-related scenes as compared to baseline. Craving varied by scene content, with scenes depicting active cocaine use eliciting the highest levels of craving. Heart rate was significantly higher in four of the scenes with drug use content and positive affect (i.e., happiness) ratings were significantly lower during cocaine scenes as compared to baseline. Overall, the results suggest that a standardized and stimulus rich virtual reality environment effectively elicits craving and physiologic reactivity. Such technology has potential utility in the development and refinement of exposure-based behavioral and pharmacological interventions for substance use disorders.     

海洛因渴求的评估与分析

目的　编制海洛因渴求量表并用于海洛因渴求症状的自评。方法　对 2 6 2名处于不同操守期的海洛因依赖者进行 10个渴求症状项目量表的自评。结果　该量表的内部一致性良好 ,Cronbacha系数为0 .92 90 (F =12 .4193　P <0 .0 0 1) ;各项目分与剩余总分的相关系数均在 0 .6 1以上 ;症状项目的聚类分析可聚成四类 ;渴求症状随操守时间的延长逐渐减轻 ,以停吸海洛因两年后减轻有统计学显著性 (P <0 .0 1)。结论　本量表适合于海洛因依赖者渴求症状的自评。     

Polydrug use and its association with drug treatment outcomes among primary heroin,methamphetamine, and cocaine users

BackgroundPolydrug use may challenge effective treatment for substance use disorders. We evaluate whether secondary substance use modifies the association between treatment and primary drug use among primary heroin, cocaine and methamphetamine (MA) users.MethodsData were obtained from prospective cohort studies on people who use illicit drugs (PWUD) in California, USA. Using repeated monthly data on self-reported secondary substance use (heroin, cocaine, MA, alcohol or marijuana; ≥1 day in a month), primary drug use (≥1 day in a month), and treatment participation, collected via timeline follow-back, we fitted generalized linear mixed multiple regression models controlling for potential confounders to examine the interactions between treatment and secondary substance use on the odds of primary heroin, cocaine and MA use, respectively.ResultsIncluded in our study were 587 primary heroin, 444 primary MA, and 501 primary cocaine users, with a median of 32.4, 13.3 and 18.9 years of follow-up, respectively. In the absence of secondary substance use, treatment was strongly associated with decreased odds of primary drug use (adjusted odds ratios (aORs): 0.25, 95% CI: 0.24, 0.27, 0.07 (0.06, 0.08), and 0.07 (0.07, 0.09)) for primary heroin, MA, and cocaine users, respectively. Secondary substance use of any kind moderated these associations (0.82 (0.78, 0.87), 0.25 (0.21, 0.30) and 0.53 (0.45, 0.61), respectively), and these findings were consistent for each type of secondary substance considered. Moreover, we observed different associations in terms of direction and magnitude between secondary substance use and primary drug use during off-treatment periods across substance types.ConclusionThis study demonstrates secondary substance use moderates the temporal associations between treatment and primary drug use among primary heroin, MA and cocaine users. Disparate patterns of polydrug use require careful measurement and analysis to inform targeted treatment for polydrug users.     

The association between executive functioning and motivation to enter treatment among regular users of heroin and/or cocaine in Baltimore,MD

This study explored the association between readiness to enter treatment and performance on the Wisconsin Card Sorting Test (WCST), a measure of problem solving ability and executive functioning. Data for this analysis was collected on 258 current regular users of heroin and/or cocaine as part of an epidemiologic study on executive function and drug use. A structural equation model was used to test the hypotheses that poorer performance on the WCST would predict lower scores on two latent constructs measuring motivation to change drug use. Specifically, poorer performance on the WCST was associated with lower recognition of problem use. Associations between treatment enrollment within the past six months and regular use of more than one drug were also observed. Findings highlight the importance of considering cognitive impairment in programs targeting active drug users and promoting treatment participation.     

Effects of biperiden on the treatment of cocaine/crack addiction: A randomised,double-blind,placebo-controlled trial

Cocaine use affects approximately 13.4 million people, or 0.3% of the world׳s population between 15 and 64 years of age. Several authors have described drug addiction as a disease of the brain reward system. Given that the cholinergic system impacts reward mechanisms and drug self-administration, acetylcholine (ACh) might play an important role in the cocaine addiction process. We evaluated the efficacy of biperiden (a cholinergic antagonist) in reducing craving and the amount used, and in increasing compliance with treatment for cocaine/crack addiction. It was a study double-blind, randomised, placebo-controlled, 8-week trial of 111 cocaine or crack addicted male patients between 18 and 50 years old. Two groups were compared: placebo (n=55) or biperiden (n=56) combined with weekly sessions of brief group cognitive-behavioural therapy. The efficacy of treatment was evaluated according to the patients’ compliance and several instruments: the Minnesota Cocaine Craving Scale, the Beck Depression and Anxiety Scales and a questionnaire assessing the amount of drug used. All of the patients attended weekly sessions for two months. We analysed the data considering the patients׳ intention to treat based on our last observation. Of the 56 patients in the biperiden group, 24 completed the treatment (42.8%) compared with only 11 patients in the placebo group (20%), which was a significant difference (p=0.009). Compliance with treatment was 118% higher in the biperiden group, which was also the group that presented a statistically significant reduction in the amount of cocaine/crack use (p<0.001). There was statistically significant difference between the craving score in the biperiden group. Pharmacological blockade of the cholinergic system with biperiden is a promising alternative to treat cocaine/crack addiction, helping patients to reduce the amount used and improving compliance with psychotherapy treatment.     

Craving predicts time to cocaine relapse: further validation of the Now and Brief versions of the cocaine craving questionnaire

BACKGROUND: The 10-item version of the cocaine craving questionnaire (CCQ-Brief) has not been validated in a mixed-gender sample, and predictive validity of the CCQ-Now and CCQ-Brief in terms of their relationship with cocaine relapse has not been demonstrated. OBJECTIVE: To further validate the CCQ-Brief in a mixed gender sample and to determine the predictive validity of the CCQ-Now and CCQ-Brief. METHOD: Seventy-two men and 51 women (Total N=123) seeking inpatient cocaine dependence treatment were administered assessments upon admission, and a prospective design was employed to assess cocaine relapse outcomes during a 90-day follow-up period after discharge from inpatient treatment. Data were analyzed using Pearson's correlation, Cox proportional hazards regression, and multiple regression. FINDINGS: The CCQ-Brief demonstrated good internal consistency and construct and concurrent validity. Both the CCQ-Now and the CCQ-Brief summary scores predicted time to cocaine relapse. In addition, the anticipation of a positive outcome from cocaine use, and intent and planning to use cocaine subscales of the CCQ-Now also predicted time to cocaine relapse. CONCLUSIONS: The CCQ-Brief was found to be a reliable and valid measure in a mixed gender sample, and both the CCQ-Now and CCQ-Brief were predictive of cocaine relapse risk. Craving assessments that go beyond desire and take into account intent and planning to use cocaine and the patient's anticipation of a positive outcome from using cocaine are likely to provide a sensitive index of cocaine relapse susceptibility. However, fear of social and clinical consequences could impact accurate reporting of cocaine craving and intent to use cocaine.     

The impact of impulsivity on cocaine use and retention in treatment

To determine whether impulsivity was related to severity of drug use and treatment outcome, 50 cocaine dependent subjects underwent baseline measures of severity of current cocaine use and the Barratt Impulsiveness Scale (BIS-11). The hypothesis of the study was that there would be a significant correlation between impulsivity and cocaine use severity. As predicted, there was a significant correlation between BIS-11 total scores and self-reported average daily cocaine use as well as cocaine withdrawal symptoms. A subset of 35 patients underwent a 12-week double-blind placebo controlled trial of buspirone and group therapy. Subjects with high baseline impulsivity remained in the study a significantly shorter period than did subjects with lower baseline impulsivity. This study shows that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment.     

The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers

Impulsivity and craving have been independently hypothesized to contribute to sustained drug use and relapse in addiction. The primary focus of this project was to determine the relationship between impulsivity and craving in 85 cocaine-dependent and 73 methamphetamine-dependent, non-treatment-seeking volunteers. Drug use was assessed with a 14-item, self-report drug and alcohol use questionnaire. Self report instruments utilized included the Barratt Impulsivity Scale (BIS) and the Visual Analog Scale (VAS), which probed “just before your last use of cocaine (for cocaine-dependent participants) or methamphetamine (for methamphetamine-dependent participants), how much craving did you experience?” The groups were similar with respect to recent use of cocaine or methamphetamine, alcohol, nicotine, and marijuana. Analysis of variance (ANOVA) did not reveal significant differences between cocaine and methamphetamine groups for total impulsivity or total craving. Simple linear regression revealed correlations between total impulsivity and total craving in cocaine (r² = 0.05, p ≤ 0.03) and methamphetamine users (r² = 0.09, p ≤ 0.008). Participants were separated into high impulsivity (HIBIS) or low impulsivity (LOBIS) subgroups using a median split. ANOVA revealed significantly higher craving in the HIBIS group versus the LOBIS group in methamphetamine users (p ≤ 0.02), but not in cocaine users. For both cocaine and methamphetamine groups, level of impulsivity and craving were found to be related to some drug use variables including years of alcohol use, severity of withdrawal, and craving level following drug use. Taken together, this study shows a marginal relationship between impulsivity and craving, which may further the understanding of motivational factors contributing to ongoing drug use and addiction in psychostimulant users.     

Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment

Individuals' use of heroin, cocaine, and alcohol during long-term methadone maintenance treatment (MMT) was studied. Prospectively collected data from 103 heroin-addicted individuals who were consecutively admitted for MMT and remained 2 years in treatment were evaluated. The patients were assessed every 6 months with a standardized interview. Three longitudinal patterns of drug abuse were identified. A proportion of patients abstained fully from their particular drug use (26% from heroin, 39% from cocaine, and 19% from alcohol); a proportion (39%, 32%, and 47%, respectively) switched between periods of abuse and nonuse of these drugs; and chronic drug users (34%, 28%, and 33%, respectively) continued use, including periods of daily abuse throughout MMT. Different therapeutic interventions may be needed in patients with different longitudinal patterns of additional substance use during MMT.     

Heroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems

The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press for IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroind and cocaine.     

Tetrodotoxin reduces cue-induced drug craving and anxiety in abstinent heroin addicts

Background

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine animals. New clinical studies suggest that low-dose TTX can safely relieve severe, treatment-resistant cancer pain. The therapeutic potential of TTX in addiction is supported by studies in laboratory animals. The purpose of this double-blind, placebo-controlled study was to assess the effect of a single intramuscular dose of TTX on cue-induced craving and anxiety in abstinent heroin addicts.

Methods

Forty-five abstinent heroin addicts were randomly assigned to three treatment groups: placebo, 5 µg TTX, or 10 µg TTX. Participants were exposed to a neutral video or a heroin-related video. Craving, anxiety, blood pressure, and heart rate were measured pre- and post-exposure.

Results

Heroin-related cues increased both craving and anxiety and had no effect on blood pressure and heart rate. A single dose of TTX dose-dependently attenuated the increases in craving and anxiety while having no effect on blood pressure or heart rate.

Conclusion

The results suggest that low-dose TTX is acutely effective in reducing cue-induced increases in heroin craving and associated anxiety.