Animal studies trigger new insights on the use of methadone maintenance

Background: Although steady-state methadone (SSM) treatment is mainly used for opioid addiction, some clinical studies indicate that it also reduces cocaine abuse in opioid-dependent individuals. Objective/methods: To present evidence suggesting that SSM may be useful in the treatment of cocaine addiction without pre-existing opioid dependence. We review studies in animals investigating the effects of SSM on behaviors motivated by cocaine and on cocaine-induced alterations of genes expression in the rat brain. Conclusion: SSM reduces cocaine intake, blocks cocaine seeking and normalizes expression of genes known to regulate cocaine seeking. These findings suggest that SSM could be an effective pharmacological agent to assist cocaine detoxification and prevention of relapse to cocaine abuse in individuals not co-dependent on opioid.     

A Treatment Algorithm for Attention Deficit Hyperactivity Disorder in Cocaine-Dependent Adults: A One-Year Private Practice Study with Long-Acting Stimulants,Fluoxetine, and Bupropion

A subgroup of adults in private treatment for cocaine dependence in remission reported a therapeutic effect from cocaine during the initial phases of cocaine addiction and, also, met DSM-IV criteria for ADHD. We report evidence that study subjects probably medicated their ADHD symptoms with cocaine and describe a 1-year treatment algorithm featuring long-acting stimulants that was effective in the management of their ADHD and cocaine dependence. Nineteen stable patients in full remission from all substance dependence were entered into an open label, prospective, treatment trial for ADHD. The treatment schedule consisted of the progressive introduction—and discontinuation of ineffective medication—of each of several medications in the following order: fluoxetine, bupropion, pemoline, sustained-release methylphenidate, dextroamphetamine spansules, and methamphetamine gradumets. Treatment of ADHD was successful. Several treatment regimens, especially those including long-acting stimulants, alone or in combination with other agents, were highly effective. All but 1 of the 19 subjects had a fully effective response for at least 1 full year. Mean UTAH scale scores were 7.4 before any medications were administered and 1.6 at the end of the study. Treatment proved successful in suppressing ADHD symptoms, with minimal cocaine slips or side effects.     

Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders

Introduction: There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived neurotropic factor (BDNF) is an important modulator of the serotonergic system and 5-HT modulates BDNF expression. Their reciprocal interaction is of crucial importance for synaptic plasticity during long-term cocaine intake. Thus, agents modifying BDNF–5-HT interactions might have therapeutic potential for cocaine dependence by reversing the altered brain structure that underlies relapse after cocaine withdrawal.

Areas covered: On the basis of the available literature, the authors propose an interaction between BDNF and the serotonergic system in the response to cocaine and during cocaine intake. Furthermore, they discuss putative therapies that are based on 5-HT and BDNF.

Expert opinion: Recent studies are beginning to elucidate the role of 5-HT and BDNF in cocaine addiction. Additionally, animal studies modeling addiction-like drug intake will only further help to gain a better understanding of how to treat cocaine addiction. Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as a modulator of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future.     

Community Reinforcement Approach (CRA) for cocaine dependence in the Spanish public health system: 1 year outcome

Introduction and Aims. The development and dissemination of effective treatments for cocaine dependence is an important public health priority in Europe, and especially in Spain, given the increase in treatment demand over recent years. The aim of this study was to determine the effectiveness of the Community Reinforcement Approach (CRA) for cocaine dependents at an outpatient clinic within the Spanish public health system. Design and Methods. A total of 82 cocaine‐dependent patients were randomly assigned to one of two treatment conditions: Standard Treatment (n = 35) or CRA (n = 47). Dependent variables were treatment retention, cocaine abstinence and composite scores from the European version of the Addiction Severity Index at 12 month follow up. Results. Of the patients who received CRA, 55% completed 6 months of treatment, versus 40% who received Standard Treatment. At the 12 month follow up, patients assigned to the CRA condition achieved higher rates of abstinence (95.2%) by comparison with Standard Treatment (69.2%). In the CRA group, 27% of the patients achieved continuous cocaine abstinence, versus 21% in the Standard Treatment group. The CRA group also obtained lower scores than the Standard Treatment group in all Addiction Severity Index composite scores. Discussion and Conclusions. This study showed that CRA is a feasible treatment for cocaine addiction in a public community setting in Spain.[Secades‐Villa R, Sánchez‐Hervás E, Zacarés‐Romaguera F, García‐Rodríguez O, Santonja‐Gómez FJ, García‐Fernández G. Community Reinforcement Approach (CRA) for cocaine dependence in the Spanish public health system: 1 year outcome. Drug Alcohol Rev 2010;30:606–612]     

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence

Rationale Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence.Objective We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects.Methods Basal PRL concentrations were assayed in 141 African–American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables.Results The basal PRL (ng/ml) in CD patients (9.28±4.13) was significantly higher than controls (7.33±2.94) (t=3.77, P<0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P<0.01), ASI-alcohol (r=0.19, P<0.05), and ASI-psychological (r=0.25, P<0.01) composite scores, and with the quantity of cocaine use (r=0.18, P<0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures.Conclusion Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence.     

Dialectical Behavior Therapy Skills Training in Alcohol Dependence Treatment: Findings Based on an Open Trial

Background: Dialectical behavior therapy (DBT) has demonstrated efficacy in treating disorders such as alcohol dependence that are characterized by emotional dysregulation. Preliminary evidence has revealed the feasibility of DBT skills training (ST) as a stand-alone treatment for such disorders. Although emotional dysregulation plays a significant role in alcohol dependence, there are no previous reports of using DBT-ST to treat it. Objectives: The aim of this study was to evaluate the duration of abstinence and changes in emotional regulation in a 3-month DBT-ST program for alcohol-dependent patients and to look for relations between abstinence and emotional regulation. Methods: We administered the Difficulties in Emotion Regulation Scale (DERS) and used urine toxicology screening to monitor alcohol/substance intake among the 244 subjects admitted to the program. Results: Among the 157 patients who completed the treatment, 73.2% were abstinent at the end of the program, and their emotional regulation improved. Improvement was independent of the initial severity of both alcohol use and emotional dysregulation. For substance use outcomes, we found a partial mediation role of improved emotional regulation. Conclusions: This is the first open trial to show improved alcohol-related behavior and emotional regulation in alcohol-dependent patients treated with DBT-ST and to posit a partial but significant relation between improved emotional regulation and alcohol use outcomes. In the treatment of alcohol dependence, emotional regulation may be a relevant factor for therapists to consider.     

Examining differential effects of psychosocial treatments for cocaine dependence: An application of latent trajectory analyses

BackgroundThe NIDA Collaborative Cocaine Treatment Study yielded different efficacies for different psychosocial treatments for cocaine dependence. However, substantial heterogeneity of patient outcomes was evident. Longitudinal data analysis techniques can be helpful in examining differential effects of psychosocial interventions on specific subpopulations of patients.MethodsOverall drug and cocaine use of 346 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions were assessed monthly during 6-month treatment. Growth mixture models were used to identify patient subgroups based on typical patterns of change in substance use during treatment and to evaluate differential treatment effects within these subgroups.ResultsThree patient subgroups following different change patterns in cocaine and overall drug use were identified irrespective of the treatment type: (a) those with moderate baseline severity of drug use and very rapid reduction of drug use during treatment, (b) those with moderate baseline severity of drug use and moderate reduction of drug use during treatment, and (c) those with severe levels of baseline drug use with moderate reduction of drug use during treatment. Patient baseline characteristics enabled discrimination between these subgroups. Individual drug counseling was most efficacious among those patients with moderate baseline severity and moderate treatment response. There were no differential treatment effects in the two other patient subgroups.ConclusionsThe population of treatment-seeking cocaine dependent individuals is heterogeneous. Research on patient subgroups with different change patterns revealed its potential to enable classifications of patients that indicate which treatment is most effective for which type of patient.     

Quality of Life,Needs, and Interest Among Cocaine Users: Differences by Cocaine Use Intensity and Lifetime Severity of Addiction to Cocaine

We examined the quality of life (QoL) of 149 patients who were recruited in 2005 at outpatient treatment centers for cocaine dependence in Spain. Important life areas and life areas with potential need and interest to change in order to improve the QoL were analyzed in terms of patients’ cocaine use intensity within the previous six months and lifetime severity addiction to cocaine. The Spanish versions of the Drug User Quality of Life Scale and the Lifetime Severity Index for Cocaine were used to measure QoL, needs and interest, and severity addiction to cocaine. The data analysis employed t-tests, linear regression, Mann–Whitney U tests, multivariate regression, and chi-square tests. Tailoring treatment programs to address the life areas that are considered relevant to cocaine users considering their intensity of consumption and lifetime severity addiction to cocaine may improve retention and treatment outcomes. Further research needs to consider patients of different ethnic backgrounds and cultural contexts. The study's limitations are noted.     

The Role of Emotion Regulation Difficulties in the Relation Between PTSD Symptoms and the Learned Association Between Trauma-Related and Cocaine Cues

Background: PTSD and cocaine dependence frequently co-occur. However, few studies have specifically examined the functional relation between trauma-related distress and cocaine use and none have examined the extent to which PTSD is associated with a learned association between trauma cues and cocaine or the underlying role of emotion regulation difficulties in this relation. Objectives: Thus, this study used a novel version of the Implicit Association Test (IAT) to examine the relation of PTSD symptoms to the strength of the trauma-cocaine cue association and the role of specific emotion regulation difficulties in this relation. Methods: A sample of 42 cocaine-dependent inpatients with a history of interpersonal traumatic exposure were recruited. Participants completed a series of questionnaires assessing PTSD symptom severity and emotion regulation difficulties. Participants then completed the IAT. Results: Results revealed a significant indirect relation of PTSD symptom severity to the strength of the trauma-cocaine cue association through the specific emotion regulation dimension of difficulties controlling impulsive behaviors when distressed. Conclusion/Importance: Results build upon extant research suggesting that factors related to emotional responding and regulation may underlie the relation between trauma-cue exposure and responses to cocaine cues among cocaine dependent patients with PTSD. The finding that PTSD symptom severity is associated with the strength of the trauma-cocaine cue association through one particular dimension of emotion regulation difficulties, difficulties controlling impulsive behaviors when distressed, highlight the potential utility of interventions focused on improving emotion regulation and impulse control abilities among trauma-exposed cocaine dependent patients.     

Mazindol Augmentation of Antipsychotic Treatment for Schizophrenic Patients with Comorbid Cocaine Abuse or Dependence

Abstract

Objectives: Cocaine abuse has a negative impact on the natural history of schizophrenia. There are no proven treatments for cocaine abuse in schizophrenia patients. The catecholamine reuptake inhibitor, mazindol, has been reported to reduce cocaine abuse in some studies. Here we report the results of a double-blind, randomized, placebo-controlled 6-week pilot study of mazindol augmentation of antipsychotic pharmacotherapy in patients diagnosed with comorbid schizophrenia and cocaine abuse or dependence.

Methods: Patients diagnosed with schizophrenia or schizoaffective disorder and cocaine abuse or dependence participated in group therapy focused on substance abuse issues and were randomly assigned to mazindol (1 mg tid, increased to 2 mg tid after 1 week) or matched placebo in addition to their current antipsychotic medication for 6 weeks.

Results: Twenty-four patients were included in the analysis, with 11 and 13 randomized to the mazindol and placebo groups, respectively. While safe and well-tolerated, mazindol was ineffective in reducing cocaine consumption, cocaine craving, and psychiatric symptoms.

Conclusions: These results do not support the efficacy of mazindol in decreasing cocaine craving, cocaine consumption, and psychiatric symptoms in schizophrenic and schizoaffective patients.     

Reduced striatal brain volumes in non-medicated adult ADHD patients with comorbid cocaine dependence

Background

Adult attention deficit/hyperactivity disorder (ADHD) is highly comorbid with other psychiatric disorders, including substance use disorders (SUD). Patients with ADHD and SUD comorbidity respond less well to pharmacological treatment (e.g., methylphenidate), have more severe ADHD symptoms, and are generally more impulsive than ADHD patients without SUD. However, little is known about structural brain abnormalities that may differentiate ADHD patients with and without comorbid SUD.

Methods

We compared regional grey matter volumes of 10 non-medicated male ADHD patients with comorbid cocaine dependence, 14 non-medicated male ADHD patients without cocaine dependence and 15 healthy control participants matched for age and premorbid intellectual functioning, using voxel-based morphometry (VBM) using both a whole-brain analysis and a priori ROI analysis based on the existing ADHD VBM literature.

Results

In a whole brain analysis, ADHD patients with and without cocaine dependence showed smaller volumes in the right putamen and cerebellum compared to healthy controls. In addition, ADHD patients without cocaine dependence showed larger volumes in the midbrain and in the precentral gyrus compared to healthy control participants and larger volumes in the occipital cortex compared to ADHD patients with comorbid cocaine dependence. A direct comparison using the a priori defined ROI approach showed that ADHD patients with cocaine dependence had smaller putamen volumes than ADHD patients without cocaine dependence.

Conclusions

ADHD patients with cocaine dependence show more profound grey matter volume reductions in the striatum compared to ADHD patients without cocaine dependence. Possible implications for treatment are discussed.     

A double-blind, placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence

Background

Acamprosate is a medication shown to be effective for the treatment of alcohol dependence. Although the exact mechanism of action of acamprosate is unknown, evidence suggests that it decreases excitatory amino acid activity by post-synaptic inhibition of the NMDA subtype of glutamate receptors. It is possible that the activity of acamprosate via modulating glutamatergic activity could also reduce craving for cocaine and impact abstinence in cocaine dependence. Therefore, we conducted a double-blind placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence.

Methods

Sixty male and female cocaine dependent patients were included in a nine week double-blind, placebo-controlled trial. After a one-week baseline, patients were randomized to receive acamprosate 666 mg three times daily or identical placebo tablets for eight weeks. The primary outcome measure was cocaine use as determined by twice weekly urine drug screens.

Results

Thirty-six patients (60%) completed the trial, with no significant between-group difference in treatment retention. Percent cocaine positive urine drug screens did not differ between the two groups. Acamprosate was no better than placebo in reducing cocaine craving, reducing cocaine withdrawal symptoms, or improving measures of drug use severity from the Addiction Severity Index. Adverse events in this trial were generally mild and were evenly distributed between the two groups.

Discussion

Acamprosate was well tolerated but was no more efficacious than placebo in promoting abstinence from cocaine in cocaine dependent patients. Acamprosate does not appear to be a promising medication for the treatment of cocaine dependence.     

Reboxetine for the treatment of patients with Cocaine Dependence Disorder

BACKGROUND: Although several approaches have been attempted for cocaine dependence, the pharmacological treatment of this serious disorder remains unclear. To date, desipramine, a tricyclic antidepressant of great noradrenergic activity, has shown the best results. Reboxetine, a selective noradrenaline reuptake inhibitor, might be an effective therapeutic option for this severe drug addiction. The aim was preliminarily to assess reboxetine in a group of cocaine dependent patients, selected from The Madrid City Council Drug Addiction Program primary care centres. METHOD: Twenty six patients with a diagnosis of cocaine dependence disorder (DSM-IV 304.20) were selected to receive open treatment with reboxetine, 8 mg/day, for 12 weeks. Follow up assessments comprised cocaine consumption, treatment retention rate and change in standard structured psychometric instrument scores: cocaine selective severity assessment, Hamilton anxiety scale, Hamilton depression scale and clinical global impression, throughout the treatment period. RESULTS: Data were obtained from 20 patients; 10 of them remained abstinent, whereas the other 10 consumed cocaine at some time during the study. The treatment retention rate at week 12 was 61.5%. The psychometric instrument mean scores showed marked decreases throughout the treatment period. CONCLUSION: Reboxetine might be an effective and safe therapeutic option for cocaine dependence disorder. The aversive effects, as well as the high blockage reported by some patients consuming cocaine during the trial, might be related to treatment. If confirmed in large clinical trials, the trends suggested by this study would confirm the role of noradrenergic function in the treatment of cocaine dependence.     

A treatment algorithm for attention deficit hyperactivity disorder in cocaine‐dependent adults: A one‐year private practice study with long‐acting stimulants,fluoxetine, and bupropion

A subgroup of adults in private treatment for cocaine dependence in remission reported a therapeutic effect from cocaine during the initial phases of cocaine addiction and, also, met DSM‐IV criteria for ADHD. We report evidence that study subjects probably medicated their ADHD symptoms with cocaine and describe a 1‐year treatment algorithm featuring long‐acting stimulants that was effective in the management of their ADHD and cocaine dependence. Nineteen stable patients in full remission from all substance dependence were entered into an open label, prospective, treatment trial for ADHD. The treatment schedule consisted of the progressive introduction—and discontinuation of ineffective medication—of each of several medications in the following order: fluoxetine, bupropion, pemoline, sustained‐release methylphenidate, dextroamphetamine spansules, and methamphetamine gradumets. Treatment of ADHD was successful. Several treatment regimens, especially those including long‐acting stimulants, alone or in combination with other agents, were highly effective. All but 1 of the 19 subjects had a fully effective response for at least 1 full year. Mean UTAH scale scores were 7.4 before any medications were administered and 1.6 at the end of the study. Treatment proved successful in suppressing ADHD symptoms, with minimal cocaine slips or side effects.     

Severity of childhood trauma is predictive of cocaine relapse outcomes in women but not men

We prospectively examined the gender-specific effects of childhood trauma on cocaine relapse outcomes in an inpatient sample of treatment engaged cocaine dependent adults. Cocaine dependent men (n=70) and women (n=54) participating in inpatient treatment for cocaine dependence were assessed on severity of childhood trauma and followed for 90 days after discharge from treatment. Greater severity of childhood emotional abuse was associated with an increased risk of relapse in women. Severity of emotional abuse, sexual abuse, and overall childhood trauma was associated with the number of days cocaine was used during follow-up in women, as was the association of severity of physical abuse and overall childhood trauma with the average amount of cocaine used per occasion. No associations between childhood trauma and cocaine relapse outcomes were found in men. These findings demonstrate that childhood trauma increases the likelihood of cocaine relapse and drug use escalation after initial relapse in women but not in men. Comprehensive assessments of childhood trauma and specialized treatments that address trauma-related pathophysiology could be of benefit in improving cocaine treatment outcomes in women.     

A placebo controlled, double-blind study of mecamylamine treatment for cocaine dependence in patients enrolled in an opiate replacement program.

A placebo controlled, double-blind trial of mecamylamine treatment of cocaine dependence was performed in methadone or LAAM maintained subjects who met DSM-IV criteria for cocaine dependence. After an eight-week placebo run-in screening period, 35 subjects were randomly assigned to receive either mecamylamine (6 mg/day) or placebo transdermal patches for a 16-week treatment period. Outcome measures included quantitative urine benzoylecognine (BE) levels, self-report of cocaine use, cocaine craving, global impression scores, mood, retention, and safety. Mecamylamine was well tolerated, and study retention did not differ by treatment group. Evidence for cocaine use, based on urine BE levels and cocaine abstinence rates, did not differ by treatment group. Self reported cocaine use, cocaine craving, and global impression scores showed moderate improvement in both groups, with a significantly greater reduction in cocaine craving (p < 0.05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support the effectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients.     

Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users

This study compared the efficacy of buprenorphine to methadone for decreasing cocaine use in patients with combined opioid and cocaine use. Participants (n=51) were enrolled in a 26-week treatment program and randomly assigned to either buprenorphine or methadone. Dosing was double-blind and double-dummy. Patients were stabilized on either 8 mg sublingual buprenorphine or 50 mg oral methadone, with dose increases given in response to continued illicit cocaine use or opioid use through week 16 of treatment. Maximum doses possible were 16 mg buprenorphine and 90 mg methadone. Average doses achieved were 11.2 mg buprenorphine and 66.6 mg methadone; 49% of the patients received the maximum doses possible. Urine samples were collected three times per week, and there was no significant difference in the rate of cocaine positive urines for the intent-to-treat sample (69% for buprenorphine versus 63% for methadone). For patients who remained in treatment through the flexible dosing period (n=28), there were significant decreases in cocaine positive urines over time (P<0.01), but no significant differences between groups or group × time effects. Buprenorphine and methadone were equally effective on measures of treatment retention, urine results for opioids, and compliance with attendance and counseling. These results demonstrate no selective efficacy of either buprenorphine or methadone in attenuating cocaine use in this population, but do provide further support for the equivalent efficacy of buprenorphine and methadone in the treatment of opioid dependence.Presented at the 55th Annual Scientific Meeting, The College on Problems of Drug Dependence, Toronto, Canada (Mune 17, 1993)     

Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [¹²³I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients.This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127.     

White Matter Integrity is Associated with Treatment Outcome Measures in Cocaine Dependence

Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users'' abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (λ₁), perpendicular eigenvalue (λ_T), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine-negative urine samples during treatment positively correlated with FA values and negatively correlated with λ₁, λ_T, and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.