5-HT induces temporomandibular joint nociception in rats through the local release of inflammatory mediators and activation of local β adrenoceptors

Objectives

The present studies assessed the effects of adolescent and adult ethanol exposure on the rewarding effects of cocaine as measured with the conditioned place preference procedure.

Methods

Male rats were exposed to intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND 65 or PND 105, respectively, and consisted of a baseline test followed by four conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the fourth conditioning cycle a final preference test was performed. Changes in time on the drug-paired side between the baseline and final test were analyzed.

Results

Animals exposed to vehicle (during adolescence or adulthood) showed a significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol (during adolescence or adulthood) showed a significant place preference at 10 mg/kg cocaine.

Conclusions

Exposure to ethanol (adolescents or adults) sensitized the rewarding effects of cocaine. This may indicate an increase in the abuse liability of cocaine following a history of ethanol exposure.     

Changed preference for sweet taste in adulthood induced by perinatal exposure to bisphenol A-A probable link to overweight and obesity

Background

The preference of obesity has risen dramatically worldwide over the past decades. Some latest reports showed significant increase of obesity in men compared to women. Implication of environmental endocrine disruptors has been focused more and more. Numerous studies in vitro and vivo implied metabolic actions of bisphenol A (BPA), however much less consideration is given to the possibility of BPA exposure-induced change in gender-specific behaviors which result in obesity and overweight.

Objectives

To examine whether perinatal exposure to BPA at relative dose to environmental levels can influence sweet preference of male and female rats and consequently lead to alteration in bodyweight.

Methods

Rats perinatally exposed to BPA at doses of 0.01, 0.1 and 1.0 mg/L were tested sweet preference for 0.25%, 0.5% saccharin and 15% sucrose by two-bottle choice (water vs. saccharin/sucrose). The food intake, liquid consumption and bodyweight of each rat were monitored daily. At the end of the test, the fat percentage and tail blood pressure were measured.

Results

Significant sex difference of preference for 0.25% and 0.5% saccharin was shown in control and all BPA-treated groups (p < 0.001, female vs. male). 0.1 and 1.0 mg/L BPA treatment induced the increase of preference for 0.25% saccharin solution in males, but not in females. 0.1 mg/L BPA treatment increased sucrose preference in males at postnatal day (PND) 70 and 140 (p < 0.05 and p < 0.001, compared to control respectively) but decreased sucrose preference in females at PND 140 (p < 0.05, compared to control). The males treated by BPA showed overweight (p < 0.001), high fat percentage (p < 0.001) and tail blood pressure (p < 0.05) than control at PND 140.

Conclusion

Perinatal exposure to a low dose of BPA could increase sweet preference of male rats. Calorie intake may be programmed during early life, leading to changes of body weight depending on the gender. Although further researches concerning the mechanism are required, the results of the present study are particularly important with regards to the more significant increasing prevalence of obesity in men and the environmental endocrine disruptors.     

Prenatal cocaine exposure and small-for-gestational-age status: effects on growth at 6 years of age

Objective

To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.

Study design

Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.

Results

At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).

Conclusions

Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.     

Psychosocial treatments for cocaine dependence: the role of depressive symptoms

Background

The association between cocaine use and depression has been frequently observed. However, less is known about the significance of depression in the treatment of cocaine use disorders. This study examined possible interrelations between drug use and depression severity among cocaine-dependent patients in psychosocial treatments for cocaine dependence.

Methods

Monthly assessed drug use and depression severity scores of N = 487 patients during 6-month psychosocial treatments for cocaine dependence were analyzed using hybrid latent growth models.

Results

Results indicated a moderate but statistically significant (z = 3.13, p < .01) influence of depression severity on increased drug use in the upcoming month, whereas drug use did not affect future depression severity.

Conclusions

Findings suggest that depression symptoms are an important predictor of drug use outcomes during psychosocial treatments for cocaine dependence and, hence, underline the importance of adequately addressing depression symptoms to improve treatment outcomes.     

Violence among men and women in substance use disorder treatment: A multi-level event-based analysis

Background

This study examined associations between acute alcohol and drug use and violence towards others in conflict incidents (overall, partner, and non-partner conflict incidents) by men and women recruited from substance use disorder (SUD) treatment.

Methods

Semi-structured interviews were used to obtain details about interpersonal conflict incidents (substance use, whether specific conflicts were with intimate partners or non-partners) in the 180 days pre-treatment. Participants for this study were selected for screening positive for past-year violence (N = 160; 77% men, 23% women).

Results

Multi-level multinomial regression models showed that after adjusting for clustering within individual participants, the most consistent predictors of violence across models were acute cocaine use (significant for overall, intimate partner and non-partner models), acute heavy alcohol use (significant for overall and non-partner models), and male gender (significant in all models).

Conclusions

This study was the first to explicitly examine the role of acute alcohol and drug use across overall, partner and non-partner conflict incidents. Consistent with prior studies using a variety of methodologies, alcohol, cocaine use and male gender was most consistently and positively related to violence severity (e.g., resulting in injury). The results provide important and novel event-level information regarding the relationship between acute alcohol and specific drug use and the severity of violence in interpersonal conflict incidents.     

Neural activation during inhibition predicts initiation of substance use in adolescence

Background

Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement.

Methods

Thirty eight adolescents from local area middle schools, ages 12-14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n = 21), or as healthy controls (CON; n = 17).

Results

At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p < .01, each cluster ≥32 contiguous voxels).

Conclusions

These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use.     

Estimated effect of prenatal cocaine exposure on examiner-rated behavior at age 7 years

Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others.

Objective

The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior.

Methods

407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software.

Results

Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß = − 0.25; 95% CI = − 0.48, − 0.02; p = 0.04) but not Sociability (estimated slope ß = − 0.03; 95% CI = − 0.26, 0.20; p = 0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p > 0.10).

Conclusions

Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.     

Deficits in default mode network activity preceding error in cocaine dependent individuals

Background

Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use.

Methods

Individuals with cocaine dependence (CD, n = 23) and demographics-matched healthy controls (HC, n = 27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping.

Results

HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use.

Conclusions

These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.     

Contingency management with community reinforcement approach or twelve-step facilitation drug counseling for cocaine dependent pregnant women or women with young children

Background

Cocaine abuse among women of child-bearing years is a significant public health problem. This study evaluated the efficacy of contingency management (CM), the community reinforcement approach (CRA), and twelve-step facilitation (TSF) for cocaine-dependent pregnant women or women with young children.

Methods

Using a 2 × 2 study design, 145 cocaine dependent women were randomized to 24 weeks of CRA or TSF and to monetary vouchers provided contingent on cocaine-negative urine tests (CM) or non-contingently but yoked in value (voucher control, VC). Primary outcome measures included the longest consecutive period of documented abstinence, proportion of cocaine-negative urine tests (obtained twice-weekly), and percent days using cocaine (PDC) during treatment. Documented cocaine abstinence at baseline and 3, 6, 9 and 12 months following randomization was a secondary outcome.

Findings

CM was associated with significantly greater duration of cocaine abstinence (p < .01), higher proportion of cocaine-negative urine tests (p < 0.01), and higher proportion of documented abstinence across the 3-, 6-, 9- and 12-month assessments (p < 0.05), compared to VC. The differences between CRA and TSF were not significant for any of these measures (all p values ≥0.75). PDC decreased significantly from baseline during treatment in all four groups (p < 0.001) but did not differ significantly between CM and VC (p = 0.10) or between TSF and CRA (p = 0.23).

Interpretation

The study findings support the efficacy of CM for cocaine dependent pregnant women and women with young children but do not support greater efficacy of CRA compared to TSF or differential efficacy of CM when paired with either CRA or TSF.     

A single-day paradigm of self-regulated human cocaine administration

Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs.

Methods

Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed.

Results

Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (“high”) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses.

Conclusions

These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).     

The reinforcing value of alcohol in a drinking to cope paradigm

Background

Alcohol use is often regarded as a means of coping with sadness and distress. The present research was conducted to explore the relation between negative mood and the reinforcing value of alcohol, while clarifying the role of coping motives.

Methods

Participants with a history of recent alcohol use (N = 44; 72% female) attended a laboratory session and were randomly assigned to either a negative (n = 22) or a neutral (n = 22) mood condition. A manipulation check confirmed that participants in the negative mood condition, but not the neutral mood condition, displayed a significant increase in negative affect. The multiple choice procedure (MCP) was used to measure the reinforcing value of alcohol after the mood manipulation.

Results

Regression models employing the MCP crossover point as the dependent variable and mood condition (neutral or negative) and drinking to cope as predictors indicated that a model with an interaction term accounted for the most variance.

Conclusions

These results suggest that the relation between mood and the reinforcing value of alcohol is moderated by drinking to cope, and help clarify the conditions under which drinking to cope may lead to negative outcomes.     

The effects of prenatal cocaine on language development at 10 years of age

Objective

To examine the long term effects of prenatal cocaine exposure (PCE) on the language development of 10-year-old children utilizing a prospective design, controlling for confounding drug and environmental factors.

Participants

Children exposed to cocaine in utero (PCE; n = 175) and non-exposed children (NCE; n = 175) were followed prospectively to 10 years of age and were compared on language subscales of the Test of Language Development-Intermediate 3rd Edition (TOLD-I:3) and phonological processing as measured by the Comprehensive Test of Phonological Processing (CTOPP).

Methods

Multivariate analysis of covariance (MANCOVA), linear regression, and logistic regressions were used to evaluate the relationship of prenatal cocaine exposure to language development, while controlling for confounders.

Results

After controlling for confounding variables, prenatal cocaine effects were observed for specific aspects of language including syntax (Sentence Combining subtest of the TOLD-I:3, p = 0.001), semantics (Malopropism subtest of the TOLD-I:3, p = 0.05) and phonological processing (Phonological Awareness subscale, p = 0.01). The caregiver factors of vocabulary, HOME, and psychological symptoms also had consistent effects on language subtests and phonological processing scores. Children with PCE who experienced foster or adoptive care had enhanced language development compared to those living with birth mothers or in relative care. Cocaine exposed girls had lower scores on the phonological awareness subscale of the CTOPP than non-exposed girls.

Conclusions

PCE has subtle effects on specific aspects of language development and phonological processing at age 10, even after controlling for confounding variables. Environmental factors (i.e., postnatal lead exposure, home environment, and caregiver vocabulary and psychological symptoms) also impact language skills at 10 years. Adoptive or foster care appears to enrich PCE children's linguistic environment and protects children against language delay in the PCE sample.     

Early adolescent cocaine use as determined by hair analysis in a prenatal cocaine exposure cohort

Background

Preclinical and other research suggest that youth with prenatal cocaine exposure (PCE) may be at high risk for cocaine use due to both altered brain development and exposure to unhealthy environments.

Methods

Participants are early adolescents who were prospectively enrolled in a longitudinal study of PCE prior to or at birth. Hair samples were collected from the youth at ages 10½ and 12½ (N = 263). Samples were analyzed for cocaine and its metabolites using ELISA screening with gas chromatography/mass spectroscopy (GC/MS) confirmation of positive samples. Statistical analyses included comparisons between the hair-positive and hair-negative groups on risk and protective factors chosen a priori as well as hierarchical logistical regression analyses to predict membership in the hair-positive group.

Results

Hair samples were positive for cocaine use for 14% (n = 36) of the tested cohort. Exactly half of the hair-positive preteens had a history of PCE. Group comparisons revealed that hair-negative youth had significantly higher IQ scores at age 10½; the hair-positive youth had greater availability of cigarettes, alcohol, and other drugs in the home; caregivers with more alcohol problems and depressive symptoms; less nurturing home environments; and less positive attachment to their primary caregivers and peers. The caregivers of the hair-positive preteens reported that the youth displayed more externalizing and social problems, and the hair-positive youth endorsed more experimentation with cigarettes, alcohol, and/or other drugs. Mental health problems, peer drug use, exposure to violence, and neighborhood characteristics did not differ between the groups. Regression analyses showed that the availability of drugs in the home had the greatest predictive value for hair-positive group membership while higher IQ, more nurturing home environments, and positive attachment to caregivers or peers exerted some protective effect.

Conclusion

The results do not support a direct relationship between PCE and early adolescent experimentation with cocaine. Proximal risk and protective factors—those associated with the home environment and preteens' caregivers—were more closely related to early cocaine use than more distal factors such as neighborhood characteristics. Consistent with theories of adolescent problem behavior, the data demonstrate the complexity of predicting pre-adolescent drug use and identify a number of individual and contextual factors that could serve as important foci for intervention.     

Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine

Background

Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown.

Objective

To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age.

Design/methods

IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n = 204) were identified by self report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n = 208) were matched (race, birth weight, maternal education, and type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n = 350) of the IDEAL study with completed 1 and/or 3 year visits (n = 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n = 356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n = 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (≥ 3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time.

Results

Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including heavy exposure, on the Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) at any or across age.

Conclusions

There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years.     

Flunitrazepam in combination with alcohol engenders high levels of aggression in mice and rats

Rationale

Higher doses of benzodiazepines and alcohol induce sedation and sleep; however, in low to moderate doses these drugs can increase aggressive behavior.

Objectives

To assess firstly the effects of ethanol, secondly the effects of flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam plus alcohol on aggression in mice and rats.

Methods

Exhaustive behavioral records of confrontations between a male resident and a male intruder were obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive and non-aggressive elements in the resident's repertoire were analyzed. Initially, the effects of ethanol (1.0 g/kg), and secondly flunitrazepam (0; 0.01; 0.1; and 0.3 mg/kg) were determined in all mice and rats; subsequently, flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3 mg/kg) was administered plus ethanol 1.0 g/kg or vehicle via gavage.

Results

The most significant finding is the escalation of aggression after a moderate dose of ethanol, and a low dose of flunitrazepam. The largest increase in aggressive behavior occurred after combined flunitrazepam plus ethanol treatment in mice and rats.

Conclusions

Ethanol can heighten aggressive behavior and flunitrazepam further increases this effect in male mice and rats.     

Executive functioning and alcohol binge drinking in university students

Background

Binge drinking (BD) is prevalent among college students. Studies on alcoholism have shown that the prefrontal cortex is vulnerable to the neurotoxic effects of alcohol. The prefrontal cortex undergoes both structural and functional changes during adolescence and young adulthood. Sex differences have been observed in brain maturation and in alcohol-induced damage. The objective of the present study was to analyze the relationship between BD and cognitive functions subserved by the prefrontal cortex in male and female university students.

Methods

The sample comprised 122 undergraduates (aged 18 to 20 years): 62 BD (30 females) and 60 non-BD (29 females). Executive functions were assessed by WMS-III (Backward Digit Span and Backward Spatial Span), SOPT (abstract designs), Letter Fluency (PMR), BADS (Zoo Map and Key Search) and WCST-3.

Results

BD students scored lower in the Backward Digit Span Subtest and generated more perseverative responses in the SOPT In relation to interaction BD by sex, BD males scored lower in the Backward Digit Span test than BD females and non-BD males.

Conclusions

BD is associated with poorer performance of executive functions subserved by the dorsolateral prefrontal cortex. The results do not support enhanced vulnerability of women to alcohol neurotoxic effects. These difficulties may reflect developmental delay or frontal lobe dysfunction.     

The psychological impact of heavy drinking among the elderly on their co-residents: the 10/66 group population based survey in the Dominican Republic

Background

There is very limited literature on alcohol use among the elderly and little is known about the impact it has on family and caregivers, especially in low and middle income countries.

Aim

To estimate the independent effect of heavy alcohol use among the elderly on the psychological health of their co-residents.

Methods

This is a secondary analysis using data from the comprehensive cross-sectional survey of the 10/66 dementia research group population-based research programme in the Dominican Republic. The characteristics of the elderly participants as well as the co-residents were described. The independent association of heavy drinking among the participants with psychological morbidity in their co-residents was estimated. Different models were generated to rule out potential mediating effects of disability and behavioural symptoms.

Results

Prevalence of heavy alcohol use in the elderly in Dominican Republic was 10.6%. There was a statistically significant independent effect of heavy alcohol use by the elderly on their co-residents mental health (PR = 1.47; 95% CI 1.07-2.01) which was not accounted by disability (Sobel-Goodman test, p = 0.15). Severity of psychological and behavioural symptoms partially (29.1% of the total effect) explained this association (Sobel-Goodman mediation test, p = 0.006).

Conclusions

Health services for the elderly in low and middle income countries will have to be configured around detection of alcohol problems among the elderly as well as offering appropriate support to their co-residents.     

Contingency management is efficacious and improves outcomes in cocaine patients with pretreatment marijuana use

Background

Marijuana use is common in patients seeking treatment for cocaine use. Nevertheless, few studies have examined effects of marijuana use on treatment outcomes in general, and even fewer with respect to contingency management (CM) treatment, which has been criticized for potentially increasing non-reinforced drug use.

Methods

Data from three randomized clinical trials of CM versus standard treatment (ST) in cocaine-abusing patients were examined ( [Petry et al., 2004], [Petry et al., 2005a] and [Petry et al., 2006a]; N = 393) to assess effects of pretreatment marijuana use on outcomes. Patients were divided into two groups: (1) no self-reported marijuana use (No Pre-M; n = 315) and (2) any self-reported marijuana use (Pre-M; n = 78) in the 30 days pretreatment.

Results

CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST. In contrast, CM exerted only modest benefits on retention in No Pre-M patients. Pretreatment marijuana use was not related to during-treatment abstinence from cocaine, opioids, and alcohol, or abstinence at a Month 9 follow-up. However, CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence. Pre-M patients also evidenced more improvements in drug problems over time when randomized to CM.

Conclusions

CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment.     

Executive dysfunction in chronic cocaine users: an exploratory study

Introduction

Chronic cocaine use is associated with some executive deficits. We assessed executive functions using ecologically valid tests in chronic cocaine users.

Objectives

To investigate the relationship between executive deficits and three measures of severity of cocaine use: years of use, quantity used, and frequency of use.

Methods

Twenty-four cocaine users were compared with twenty-seven community controls. We used Student's t-test and Chi-squared to compare means and categorical variables, respectively. Linear regression analyses for the adjusted comparative analysis between cases and controls, and severity of cocaine use among cocaine users were performed.

Results

Chronic cocaine users performed worse on measures of attention and working memory (Forward and Backward Digit Span, p < .001), set-shifting abilities (difference score between the Trail Making B and A, TMB-A, p = .006), cognitive test of mental flexibility and response inhibition (Rule Shift Cards) (p < .001), and prefrontal functioning (Wisconsin Card Sorting Test, WCST, p = .023) than controls. Years of cocaine use were associated with deficits in the Backward Digit Span (p = .041; CI 95%: −.760 to −.002), the TMB-A (p = .026; CI 95%: .687 to 9.761), the Zoo Map (p = .034; CI 95%: −.480 to −.021), and the Rule Shift Cards (p = .006; CI 95%: −.836 to −.164), among others. Quantity of cocaine use was associated with executive deficits measured by the Forward Digit Span (p = .007; CI 95%: −.727 to −.133), the TMB-A (p = .021; CI 95%: 5.304-57.945), and the number of perseverative errors in the WSCT (p = .002; CI 95%: −10.654 to −2.800). Frequency of cocaine was associated with deficits in the Backward Digit Span (p = .042; CI 95%: −1.548 to −.030).

Conclusions

Chronic use of cocaine is associated with executive deficits, which may influence patients’ functionality, prognosis, and therapeutic failure.