Days Of Cocaine Use Research Articles

Polysubstance use before and during treatment with medication for opioid use disorder: Prevalence and association with treatment outcomes

ObjectivePolysubstance use may complicate treatment outcomes for individuals who use opioids. This research aimed to examine the prevalence of polysubstance use in an opioid use disorder treatment trial population and polysubstance use's association with opioid relapse and craving. MethodsThis study is a secondary data analysis of individuals with opioid use disorder who received at least one dose of medication (n = 474) as part of a 24-week, multi-site, open label, randomized Clinical Trials Network study (CTN0051, X:BOT) comparing the effectiveness of extended-release naltrexone versus buprenorphine. Models examined pretreatment polysubstance use and polysubstance use during the initial 4 weeks of treatment on outcomes of relapse by week 24 of the treatment trial and opioid craving. ResultsPolysubstance use was generally not associated with treatment outcomes of opioid relapse and craving. Proportion of days of pretreatment sedative use was associated with increased likelihood of opioid relapse (OR: 1.01, 95 % CI: 1.00–1.02). Proportion of days of cocaine use during the initial 4 weeks of treatment was associated with increased likelihood of opioid relapse (OR: 1.05, 95 % CI: 1.01–1.09) but this effect was no longer significant once the potential of confounding by opioid use was considered. Sedative use during initial 4 weeks of treatment was associated with increased opioid craving (b: 0.77, 95 % CI: 0.01–1.52). The study found no other significant relationships. ConclusionsIn the current study population, polysubstance use was only marginally associated with 24-week treatment outcomes.

Socioeconomic inequalities and Black/White disparities in US cocaine-involved overdose mortality risk.

This study examined whether socioeconomic inequalities account for Black/White disparities in: (a) the prevalence of potential risk factors for overdose among adults using cocaine; and (b) national mortality rates for cocaine-involved overdose. Data from 2162 Non-Hispanic (NH) Black or White adults (26 +) who reported past-year cocaine use in the 2015-2019 National Survey of Drug Use and Health were analyzed to obtain predicted probabilities of potential overdose risk factors by race and sex, using marginal effects via regression analyses, adjusting for age and socioeconomic indicators. Next, National Center for Health Statistics data (for 47,184 NH Black or White adults [26 +] who died of cocaine-involved overdose between 2015 and 2019) were used to calculate cocaine-involved overdose mortality rates by race and sex across age and educational levels. Several potential overdose vulnerabilities were disproportionately observed among NH Black adults who reported past-year cocaine use: poor/fair overall health; cocaine use disorder; more days of cocaine use yearly; hypertension (for women); and arrests (for men). Adjusting for age and socioeconomic indicators attenuated or eliminated many of these racial differences, although predicted days of cocaine use per year (for men) and cocaine use disorder (for women) remained higher in NH Black than White adults. Cocaine-involved overdose mortality rates were highest in the lowest educational strata of both races; nonetheless, Black/White disparities were observed even at the highest level of education, especially for adults ages 50 + . Age and socioeconomic characteristics may account for some, yet not all, of Black/White disparities in vulnerability to cocaine-involved overdose.

Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial

BackgroundCocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing. ObjectiveThis multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD. MethodsrTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use. ResultsForty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline. ConclusionsA significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group.Clinical trial registration details:clinicaltrials.govidentifierNCT03333460

A randomised, double-blind, sham-controlled study of left prefrontal cortex 15 Hz repetitive transcranial magnetic stimulation in cocaine consumption and craving.

Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9-10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p<0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p<0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups. In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. The study number on clinicalTrials.gov is NCT03607591.

Detecting change in psychiatric functioning in clinical trials for cocaine use disorder: sensitivity of the Addiction Severity Index and Brief Symptom Inventory

BackgroundAssessment instruments commonly used in clinical trials to measure functional outcomes in substance users may lack sensitivity to detect change during treatment, potentially limiting findings regarding benefits of reduced drug use. This study evaluated the sensitivity of the Addiction Severity Index (ASI) to detect change in psychiatric functioning among cocaine users. MethodsData were pooled across five clinical trials for cocaine use disorder (N = 492) that included a 12-week treatment period and 6-month follow-up. Within-person cohen’s d′ was used to evaluate effect size of change on the Psychiatric Composite Score of the ASI (ASI-Psych) and Global Severity Index (GSI) of the Brief Symptom Inventory, as well as cocaine use. ResultsEffect sizes were larger for GSI than ASI-Psych from baseline to week 12 (GSI d′ = 0.59; ASI-Psych d′ = 0.16), and 6-month follow-up (GSI d′ = 0.48; ASI-Psych d′ = 0.10). For those with non-zero ASI-Psych at baseline (n = 252), medium effect sizes were found over the 12-week period (d′ = 0.53) and 6-month follow-up (d′ = 0.47). Effect sizes for change in days of cocaine use were most similar to GSI in either sample. ConclusionsThe ASI Psychiatric Composite Score may have limited sensitivity to detect change in psychiatric functioning among clinical trial participants who reduce cocaine use. It may be useful for detecting change amongst those reporting some psychiatric problems at the start of treatment. Future research should consider an instrument’s sensitivity to change when assessing the potential functional benefits of reducing cocaine use.

Reward-Related Responses and Tonic Craving in Cocaine Addiction: An Imaging Study of the Monetary Incentive Delay Task.

BackgroundCocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses were mixed, and few studies have examined whether reward responses relate to tonic cocaine craving.MethodsWe combined functional magnetic resonance imaging and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines, and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine-dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use.ResultsThe VS showed higher activation to large as compared with small or no wins, but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses.ConclusionsThe results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving, and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug-seeking behavior in addicted individuals.

Longitudinal patterns of cocaine use among patients receiving injectable hydromorphone or diacetylmorphine for the treatment of opioid use disorder: A growth curve modeling approach

Background and aimsCocaine use is prevalent among people receiving injectable opioid agonist treatment. Investigations of cocaine use in this population have been descriptive and the potential heterogeneity existing in patterns of use have not been characterized. As such, among patients receiving injectable opioid agonist treatment, this study aimed to: 1) quantify intra- and inter-individual variation in cocaine use over 24-months and; 2) determine how predictors of interest explained this variation. MethodsParticipants were patients receiving injectable opioid agonist treatment for opioid use disorder. Study visits were completed at baseline prior to receiving treatment, and 3,6,9,12,18, and 24 months after baseline. A multi-level regression approach to growth curve modeling was employed to estimate and explain intra- (within-person) and inter-individual (between-person) variation in cocaine use. ResultsSignificant intra and inter-individual variation in cocaine use was identified over 24-months. Treatment engagement was on average associated with reductions in the prior month number of days of cocaine use (range: 0–30)(Estimate (standard error): -0.05(0.02), p = 0.003). On average, men reported less cocaine use compared to women (Estimate (standard error): -5.91(1.57), p=<0.001), and participants reporting ever regularly using cocaine at baseline reported more cocaine use over 24-months compared to participants reporting never regularly using cocaine (Estimate (standard error): 4.72 (1.91), p = 0.013). ConclusionsSignificant reductions in cocaine use were observed and significant heterogeneity in patterns of cocaine use was identified. These heterogeneous cocaine use profiles suggest that an individualized approach to care will be critical in responding to patients’ cocaine use in injectable opioid agonist treatment.

Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence.

BackgroundIndividuals with cocaine addiction are characterized by under-responsiveness to natural reinforcers. As part of the dopaminergic pathways, the hypothalamus supports motivated behaviors. Rodent studies suggested inter-related roles of the hypothalamus in regulating drug and food intake. However, few studies have investigated hypothalamic responses to drugs and food or related cues in humans.MethodsWe examined regional responses in 20 cocaine-dependent and 24 healthy control participants exposed to cocaine/food (cocaine dependent) and food (healthy control) vs neutral cues during functional magnetic resonance imaging. We examined the relationship between imaging findings and clinical variables and performed mediation analyses to examine the inter-relationships between cue-related activations, tonic cocaine craving, and recent cocaine use.ResultsAt a corrected threshold, cocaine-dependent participants demonstrated higher activation to cocaine than to food cues in the hypothalamus, inferior parietal cortex, and visual cortex. Cocaine-dependent participants as compared with healthy control participants also demonstrated higher hypothalamic activation to food cues. Further, the extent of these cue-induced hypothalamic activations was correlated with tonic craving, as assessed by the Cocaine Craving Questionnaire, and days of cocaine use in the prior month. In mediation analyses, hypothalamic activation to cocaine and food cues both completely mediated the relationship between the Cocaine Craving Questionnaire score and days of cocaine use in the past month.ConclusionsThe results were consistent with the proposition that the mechanisms of feeding and drug addiction are inter-linked in the hypothalamus and altered in cocaine addiction. The findings provide new evidence in support of hypothalamic dysfunction in cocaine addiction.

Using a data science approach to predict cocaine use frequency from depressive symptoms

BackgroundDepressive symptoms may contribute to cocaine use. However, tests of the relationship between depression and severity of cocaine use have produced mixed results, possibly due to heterogeneity in individual symptoms of depression. Our goal was to establish which symptoms of depression are most strongly related to frequency of cocaine use (one aspect of severity) in a large sample of current cocaine users. We utilized generalized additive modeling to provide data-driven exploration of the relationships between depressive symptoms and cocaine use, including examination of non-linearity. We hypothesized that symptoms related to anhedonia would demonstrate the strongest relationship to cocaine use. Method772 individuals screened for cocaine use disorder treatment studies. To measure depressive symptoms, we used the items of the Beck Depression Inventory, 2nd Edition. Cocaine use frequency was measured as proportion of self-reported days of cocaine use over the last 30 days using the Addiction Severity Index. ResultsModels identified 18 significant predictors of past-30-day cocaine use. The strongest predictors were Crying, Pessimism, Changes in Appetite, Indecisiveness, and Loss of Interest. Noteworthy effect sizes were found for specific response options on Suicidal Thoughts, Worthlessness, Agitation, Concentration Difficulty, Tiredness, and Self Dislike items. ConclusionsThe strongest predictors did not conform to previously hypothesized “subtypes” of depression. Non-linear relationships between items and use were typical, suggesting BDI-II items may not be monotonically increasing ordinal measures with respect to predicting cocaine use. Qualitative analysis of strongly predictive response options suggested emotional volatility and disregard for the future as important predictors of use.

Treatment outcomes among a cohort of African American buprenorphine patients: Follow-up at 12 months

ABSTRACTBackground: Although buprenorphine/naloxone (bup/nal) is well-established as a safe and effective treatment for opioid use disorders (OUDs), there are few studies reporting 12-month outcomes of patients receiving bup/nal in formerly drug-free outpatient programs. Objectives: To examine 12-month outcomes by bup/nal treatment enrollment status among a cohort of African American patients enrolled in a clinical trial. Methods: This analysis builds upon a randomized trial of 300 opioid-dependent African American bup/nal patients in two outpatient programs in Baltimore, MD. A subset of participants (N = 133, n = 47 female) were tracked for a 12-month follow-up interview. Results: The participants receiving bup/nal at 12 months had significantly fewer opioid-positive urine screens (44% v. 73%) and days of self-reported heroin use (M [SE] = 1.13 [.34] v. 7.12 [1.44]) than the out-of-bup/nal-treatment group (both ps ≤ .001). Similarly, those receiving bup/nal reported significantly fewer days of cocaine use (M [SE] = 0.85 [0.23] v. 2.88[0.75]) and alcohol use (M [SE] = 1.44 [0.38] v. 3.69 [1.04]; both ps<.05). There were no significant differences related to criminal activity, quality of life, and most ASI composite scores. Models adjusting for the baseline value, prior treatment experience, and assigned study condition largely confirmed these findings, except that participants in treatment had fewer days of crime and higher psychological quality of life scores compared to those out-of-treatment. Conclusions: Those receiving bup/nal at 12 months had significantly lower rates of illicit opioid use than those who were not. Approaches to improve bup/nal treatment retention and reengagement of patients with OUD are needed.

Comparable efficacy of behavioral and pharmacological treatments among African American and White cocaine users

ABSTRACTMultiple randomized clinical trials (RCTs) have evaluated a range of treatments for cocaine dependence, but few of these have focused specifically on the racial diversity observed among cocaine-dependent patients. The present analyses evaluated racial variation in cocaine use and addiction-related psychosocial outcomes at baseline and follow-up among 388 African American and White adults participating in 1 of 5 RCTs evaluating a range of pharmacological and behavioral treatments for cocaine use disorders. General linear modeling (GLM) indicated significant racial variation in cocaine and psychosocial indicators at baseline. At baseline, there were significant racial differences in the number of days paid for work in the 30 days prior to the study, age, days of cocaine use in the past month, age of first cocaine use, psychosocial problems (i.e., employment, cocaine, legal, and family), public assistance status, and prevalence of lifetime anxiety disorders. There were no significant main or interaction effects of race and study on treatment outcomes at posttreatment. These findings suggest that despite significant racial differences at baseline, the pharmacological and behavioral treatments resulted in fairly comparable outcomes across racial groups in these 5 RCTs.

Patient Pre-Treatment Expectations Do Not Predict Cocaine Use Outcomes: Data From Four Clinical Trials

ABSTRACTBackground: There are very few data regarding the extent to which patients' initial expectations regarding treatment are associated with substance use treatment outcomes. Objective: This study sought to determine how patients' treatment expectations were associated with treatment outcomes. Methods: This study explored patient pre-treatment expectations and substance use treatment outcomes for 387 individuals participating in treatment for cocaine use within the United States (68.2% male, mean age 36 years old, 54.8% Caucasian). Results: Participants' expectations regarding abstinence were not strongly associated with post-treatment or follow-up cocaine use outcome measures. There was a significant association between the expected timeframe of receiving a positive treatment effect (i.e., outcome efficiency expectations) and days of cocaine use at the 1-month follow-up point (F = 3.45, p =.009). Post-hoc comparisons revealed that participants that expected positive effects of treatment within 0–1 week reported fewer days of cocaine use than those that expected results in 1–2 months. Also, those that expected positive effects of treatment in 1–2 months reported more cocaine use than those who expected positive results within two weeks to one month. Further, there was a significant effect of outcome efficiency expectations on a proxy measure of achieving a good treatment outcome at the three-month follow-up point (F = 11.13, p =.025). Conclusions/Importance: Results suggest that treatment outcomes are not associated with patients' treatment outcome expectations, but that some outcomes are associated with treatment outcome efficiency expectations.

Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial.

Heroin-assisted treatment is effective for methadone treatment-refractory heroin-dependent patients, but continued comorbid cocaine dependence remains problematic. Sustained-release dexamfetamine is a promising agonist pharmacotherapy for cocaine dependence and we aimed to assess its acceptance, efficacy, and safety. In this multicentre, randomised, double-blind, placebo-controlled trial, patients who were treatment-refractory, as indicated by at least two earlier failed treatments aimed at reducing or abstaining from cocaine use, and who regularly (≥8 days/month) used crack-cocaine were enrolled from four heroin-assisted treatment centres in the Netherlands. Eligible patients were randomly assigned (1:1) to receive either 12 weeks of daily, supervised prescription of 60 mg/day oral sustained-release dexamfetamine or placebo in addition to co-prescribed methadone and diacetylmorphine. Randomisation was done by the collaborating pharmacist, using a computer-generated random number sequence with stratification by treatment centre in blocks of four per stratum. Randomisation was masked to patients, staff, and researchers throughout the study. The primary outcome was the number of self-reported days of cocaine use during study treatment, assessed every 4 weeks. Primary and safety analyses were done in the intention-to-treat population. The study was registered with the European Union Drug Regulating Authorities Clinical Trials (EUdraCT 2013-004024-11) and with The Netherlands Trial Register (NTR2576). Between Aug 8, 2014, and Feb 27, 2015, 111 patients were assessed for eligibility, of whom 73 were enrolled and randomised; 38 patients were assigned to the sustained-release dexamfetamine group and 35 to the placebo group. Sustained-release dexamfetamine treatment resulted in significantly fewer days of cocaine use than placebo treatment (mean 44·9 days [SD 29·4] vs 60·6 days [24·3], respectively [95% CI of difference 3·1-28·4]; p=0·031; Cohen's standardised effect size d=0·58). One or more adverse events were reported by 28 (74%) patients in the dexamfetamine group and by 16 (46%) patients in the placebo group. Most adverse events were transient and well-tolerated. Sustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management. Netherlands Organisation for Health Research and Development.

Effective drug therapy for cocaine dependence: a milestone.

In The Lancet, Mascha Nuijten and colleagues 1 Nuijten M Blanken P van de Wetering B Nuijen B van den Brink W Hendriks VM Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016; (published online March 22.)http://dx.doi.org/10.1016/S0140-6736(16)00205-1 Google Scholar present the results of a multicentre, randomised, double-blind, placebo-controlled trial assessing the acceptance, safety, and efficacy of sustained-release dexamfetamine in cocaine-dependent patients on heroin-assisted treatment. The study findings showed that 60 mg/day oral sustained-release dexamfetamine over 12 weeks was well accepted, safe, and superior to placebo in terms of days of cocaine use (mean 44·9 days [SD 29·4] in the sustained-release dexamfetamine group vs 60·6 days [24·3] in the placebo group [95% CI of difference 3·1–28·4]; p=0·031; Cohen's standardised effect size d=0·58) and all self-reported and urine-based cocaine use-related outcomes. Cocaine dependence is prevalent throughout the world and causes major morbidity and mortality. 2 Degenhardt L Hall W Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet. 2012; 379: 55-70 Summary Full Text Full Text PDF PubMed Scopus (868) Google Scholar At present, no effective pharmacotherapy exists. Agonist replacement therapy has been successfully applied to opioid and tobacco dependence, 3 Strain EC Bigelow GE Liebson IA Stitzer ML Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA. 1999; 281: 1000-1005 Crossref PubMed Scopus (359) Google Scholar , 4 Aubin HJ Luquiens A Berlin I Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Br J Clin Pharmacol. 2014; 77: 324-336 Crossref PubMed Scopus (73) Google Scholar but previous studies examining this approach in cocaine dependence failed to find statistically significant benefits in terms of reduced cocaine use, or showed indecisive results. This could be due to limitations in the methods, such as small sample sizes, 5 Shearer J Wodak A van Beek I Mattick RP Lewis J Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Addiction. 2003; 98: 1137-1141 Crossref PubMed Scopus (120) Google Scholar inadequate dosing schemes, 6 Dursteler KM Berger EM Strasser J et al. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence. Subst Abuse Rehabil. 2015; 6: 61-74 Crossref PubMed Google Scholar or large attrition rates. 7 Grabowski J Rhoades H Stotts A et al. Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials. Neuropsychopharmacology. 2004; 29: 969-981 Crossref PubMed Scopus (168) Google Scholar The study by Nuijten and colleagues 1 Nuijten M Blanken P van de Wetering B Nuijen B van den Brink W Hendriks VM Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016; (published online March 22.)http://dx.doi.org/10.1016/S0140-6736(16)00205-1 Google Scholar overcomes most of these shortcomings. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trialSustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management. Full-Text PDF

Predictors of non-use of illicit heroin in opioid injection maintenance treatment of long-term heroin dependence

AimsTo investigate baseline and concurrent predictors of non-use of illicit heroin among participants randomized to injectable opioids in the North American Opiate Medication Initiative (NAOMI) clinical trial. MethodsNAOMI was an open-label randomized controlled trial comparing the effectiveness of injectable diacetylmorphine and hydromorphone for long-term opioid-dependency. Outcomes were assessed at baseline and during treatment (3, 6, 9, 12months). Days of non-use of illicit heroin in the prior month at each follow-up visit were divided into three categories: Non-use; Low use (1 to 7days) and High use (8days or more). Tested covariates were: Sociodemographics, Health, Treatment, Drug use and illegal activities. Mixed-effect proportional odds models with random intercept for longitudinal ordinal outcomes were used to assess the predictors of the non-use of illicit heroin. Results139 participants were included in the present analysis. At each follow-up visit, those with non-use of illicit heroin represented 47.5% to 54.0% of the sample. Fewer days of cocaine use (p=0.074), fewer days engaged in illegal activities at baseline (p<0.01) and at each visit (p<0.01), less money spent on drugs (p<0.001), days with injection opioid or oral methadone treatment (p<0.001) and total mg of injectable opioids taken (p<0.001), independently predicted lower use of illicit heroin. ConclusionsThe independent effect of several concurrent factors besides the injection of opioid dose suggests benefits from the clinic that go beyond the provision of the medication alone. Thus, this supervised model of care presents an opportunity to maximize the beneficial impact of medical and psychosocial components of the treatment on improving outcomes associated with non-use of illicit heroin.

Progesterone for the reduction of cocaine use in post-partum women with a cocaine use disorder: a randomised, double-blind, placebo-controlled, pilot study

Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. US National Institute on Drug Abuse; Veterans Administration.

Hippocampal volume mediates the relationship between measures of pre-treatment cocaine use and within-treatment cocaine abstinence

BackgroundData suggest that the amygdala and hippocampus contribute to cocaine seeking and use, particularly following exposure to cocaine-related cues and contexts. Furthermore, indices of pre-treatment cocaine-use severity have been shown to correlate with treatment outcome in cocaine-dependent patients. MethodsThe aim of this study was to assess the relationships between amygdalar and hippocampal volumes and cocaine use before and during treatment. High-resolution magnetic-resonance brain images were obtained from 23 cocaine-dependent patients prior to treatment and 54 healthy comparison individuals. Automated segmentation of the amygdala and hippocampus images was performed in FreeSurfer. Cocaine-dependent patients subsequently received behavioral therapy alone or combined with contingency management as part of a treatment trial, and cocaine-use indices (self-report, urine toxicology) were collected. ResultsComparison participants and cocaine-dependent patients did not show significant difference in amygdalar and hippocampal volumes at pre-treatment. Within the patient group, greater hippocampal volumes were correlated with more days of cocaine use before treatment and with poorer treatment outcome as indexed by shorter durations of continuous abstinence from cocaine and lower percentages of cocaine-negative urine samples during treatment. Mediation analysis indicated that pre-treatment hippocampal volumes mediated the relationships between pre-treatment cocaine use and treatment outcomes. ConclusionsThe finding of a significant correlation between hippocampal volume and pre-treatment cocaine-use severity and treatment response suggests that hippocampal volume should be considered when developing individualized treatments for cocaine dependence.

Prospective risk factors for traumatic event reexposure in community syringe exchange participants

BackgroundTraumatic event reexposure in injecting drug users is associated with increased drug use and potential for psychiatric symptoms. This is the first study to examine fixed and time-varying factors that are prospectively associated with new traumatic event reexposure in injecting drug users. MethodsInjecting drug users registered in a syringe exchange program were enrolled in a 16-month parent study comparing strategies to increase drug abuse treatment enrollment. Participants (N=162) completed baseline measures of demographics, psychiatric treatment history, and lifetime traumatic event exposure. Monthly follow-ups assessed past-month traumatic event exposure, days of heroin and cocaine use, criminal activity, and drug abuse treatment participation. Generalized estimating equations models tested the influence of fixed baseline and time-varying factors on traumatic event reexposure in the same month, the following month, and two months later. ResultsSignificant fixed risk factors for traumatic event reexposure include female gender and past psychiatric treatment. In addition, each past traumatic event exposure was associated with an increased likelihood of reexposure. After accounting for all other factors, each day of cocaine use was associated with a small but persistent increased risk of traumatic event reexposure. Reexposure to a traumatic event in the prior month more than doubled the risk of subsequent reexposure. ConclusionsInjecting drug users experience a pattern in which drug use is associated with increased risk of subsequent traumatic event reexposure, and traumatic event reexposure is associated with further drug use and continued reexposure. Implications for addressing these concerns in injecting drug users are presented.

Error-Related Brain Activity as a Biomarker for Cocaine Relapse

Addiction is characterized by the observation that substance-dependent individuals continue to use substances despite the negative consequences, such as social, interpersonal, or physical problems. The ability to adequately monitor negative consequences in behavior, referred to as error processing, is necessary for optimal behavioral performance to guide one's behavior toward one's long-term goals (eg, maintain abstinence from substance use). It has been previously reported that cocaine-dependent individuals show a decreased sensitivity to errors and this has been attributed to reduced activation in the anterior cingulate cortex (ACC; Kaufman et al, 2003). Likewise, electrophysiological research has shown that the error-related negativity (ERN)—which represents the brain's automatic detection of an error—is reduced in cocaine users compared with healthy controls (Franken et al, 2007). It has been theorized that a reduced ERN is a representation of the notion that errors are perceived as less meaningful or motivationally relevant in substance-dependent individuals (Hajcak, 2012). This may underlie their persistence of drug taking despite the clear adverse consequences. Additionally, it is conceivable that these brain dysfunctions associated with error processing also have a role in drug relapse. Error processing is typically measured using reaction time tasks with high chances to make errors, such as the Go-Nogo task or Eriksen flanker task. To examine the predictive role of error processing in drug relapse, we measured event-related potentials (ERPs) in response to an Eriksen flanker task in cocaine-dependent patients during their first week of detoxification treatment (Marhe et al, 2013). In this task, letter strings are presented and participants are required to respond as quickly and accurately as possible to a target letter. This task is frequently used to measure error processing, as participants easily make mistakes on this task. First, the results confirmed that the ERN amplitude was indeed reduced in cocaine-dependent patients as compared with non-dependent controls. Most interestingly, ERN amplitude predicted cocaine use after treatment, over and above other relevant predictors measured at baseline such as substance use severity and subjective cocaine craving. A reduced ERN at baseline was associated with a higher number of days of cocaine use at 3-month follow-up. Another recent study using functional magnetic resonance imaging found that the reduced error-related brain activity in areas such as the dorsal ACC, thalamus, and insula is associated with cocaine relapse after treatment (Luo et al, 2013). The results of both these studies indicate that cocaine-dependent patients exhibiting underactive error-related brain activity are more at risk of relapse. Error-related brain activity might serve as a biomarker helping to identify patients vulnerable for relapse already early in treatment. Although there is knowledge on the underlying brain processes of error processing (Kaufman et al, 2003; Luo et al, 2013), further investigation of the underlying neural circuitry and neurochemistry using neuroimaging and (combined) pharmacological approaches will further advance this research area. Regarding the results of Marhe et al (2013), it could be beneficial in the future to routinely assess the ERN amplitude in cocaine-dependent patients at the start of detoxification treatment. The idea to use electroencephalography (EEG) as a screening instrument has gained interest, specifically for ERP components that have good psychometric properties, such as the ERN (Hajcak, 2012; Hoffmann and Falkenstein, 2012). In addition, EEG is a noninvasive, relative inexpensive, and accessible biomarker. Therefore, it would be very feasible to use this measure in large-scale (genetic) studies. Future studies should reconfirm the association between the ERN and drug relapse and further examine the sensitivity and specificity of the ERN as a predictor of cocaine relapse. Ultimately, treatment programs could be tailored to the patient's need to improve outcomes.

Error-Related Brain Activity Predicts Cocaine Use After Treatment at 3-Month Follow-up

Relapse after treatment is one of the most important problems in drug dependency. Several studies suggest that lack of cognitive control is one of the causes of relapse. In this study, a relative new electrophysiologic index of cognitive control, the error-related negativity, is investigated to examine its suitability as a predictor of relapse. The error-related negativity was measured in 57 cocaine-dependent patients during their first week in detoxification treatment. Data from 49 participants were used to predict cocaine use at 3-month follow-up. Cocaine use at follow-up was measured by means of self-reported days of cocaine use in the last month verified by urine screening. A multiple hierarchical regression model was used to examine the predictive value of the error-related negativity while controlling for addiction severity and self-reported craving in the week before treatment. The error-related negativity was the only significant predictor in the model and added 7.4% of explained variance to the control variables, resulting in a total of 33.4% explained variance in the prediction of days of cocaine use at follow-up. A reduced error-related negativity measured during the first week of treatment was associated with more days of cocaine use at 3-month follow-up. Moreover, the error-related negativity was a stronger predictor of recent cocaine use than addiction severity and craving. These results suggest that underactive error-related brain activity might help to identify patients who are at risk of relapse as early as in the first week of detoxification treatment.