Treatment Of Cocaine Use Disorder Research Articles

Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-HT1A and TRPV1 receptor mechanisms

Cocaine abuse continues to be a serious health problem worldwide. Despite intense research there is currently no FDA-approved medication to treat cocaine use disorder. The recent search has been focused on agents targeting primarily the dopamine system, while limited success has been achieved at the clinical level. Cannabidiol (CBD) is a U.S. FDA-approved cannabinoid for the treatment of epilepsy and recently was reported to have therapeutic potential for other disorders. Here we systemically evaluated its potential utility for the treatment of cocaine use disorder and explored the underlying receptor mechanisms in experimental animals. Systemic administration (10–40 mg/kg) of CBD dose-dependently inhibited cocaine self-administration, shifted a cocaine dose-response curve downward, and lowered break-points for cocaine self-administration under a progressive-ratio schedule of reinforcement. CBD inhibited cocaine self-administration maintained by low, but not high, doses of cocaine. In addition, CBD (3–20 mg/kg) dose-dependently attenuated cocaine-enhanced brain-stimulation reward (BSR) in rats. Strikingly, this reduction in both cocaine self-administration and BSR was blocked by AM630 (a cannabinoid CB2 receptor antagonist), WAY100135 (a 5-HT1A receptor antagonist), or capsazepine (a TRPV1 channel blocker), but not by AM251 (a CB1 receptor antagonist), CID16020046 (a GPR55 antagonist), or naloxone (an opioid receptor antagonist), suggesting the involvement of CB2, 5-HT1A, and TRPV1 receptors in CBD action. In vivo microdialysis indicated that pretreatment with CBD (10–20 mg/kg) attenuated cocaine-induced increases in extracellular dopamine (DA) in the nucleus accumbens, while CBD alone failed to alter extracellular DA. These findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine via a DA-dependent mechanism.

Randomized placebo-controlled trial of galantamine in individuals with cocaine use disorder

No pharmacotherapies are approved for the treatment of cocaine use disorder (CUD). Galantamine, a cholinesterase inhibitor, has shown initial promise for cocaine use reduction in methadone-maintained individuals with CUD and cognitive improvement in abstinent individuals with past CUD. However, galantamine has not previously tested in individuals with current CUD and no comorbid opioid use disorder or methadone maintenance. The goal of this 13-week, double-blind, placebo-controlled, randomized controlled trial was to test the efficacy of galantamine (8 mg or 16 mg/day; extended release (ER)) for reducing cocaine use and improving cognitive function in individuals with cocaine use disorder (CUD). Ninety-three treatment-seeking cocaine users were randomized to placebo (n = 32), 8 mg/day galantamine (n = 31) or 16 mg/day galantamine (n = 30). The medication was well-tolerated with minimal reports of side-effects. However, there were no significant treatment group differences in cocaine use outcomes (as measured by self-report or urines). The 16 mg galantamine group had a greater improvement in working memory capacity (Backwards Digit Span), but there were no other significant treatment group differences on key cognitive outcomes. These findings did not provide support for the efficacy of galantamine as a treatment for cocaine use in this sample of individuals with CUD.

Contingency management is effective in promoting abstinence and retention in treatment among crack cocaine users with a previous history of poor treatment response: a crossover trial

BackgroundCrack use has become a severe health problem in Brazil. Contingency management has shown robust evidence of efficacy in the treatment of cocaine use disorder (CUD) in high-income countries; however, it is still unclear how this intervention can impact treatment in low-income countries.ObjectiveTo evaluate the efficacy of contingency management in the treatment of CUD among individuals with a previous history of poor treatment response in Brazil.MethodsSix months after the end of treatment, 32 participants previously allocated to the usual care condition (UCC) were invited to receive an additional 12 weeks of treatment in a contingency management condition (CMC), and 16 accepted the invitation. We compared data obtained from only the 16 participants (14 male) exposed to both treatment conditions.ResultsParticipants attended more treatment sessions and were retained in treatment for a longer period during the CMC than during the UCC (p < .01 for both). The proportion of negative cocaine samples submitted, the mean longest duration of cocaine abstinence, and the odds of being abstinent from cocaine during the 12 weeks of treatment were significantly higher during treatment in the CMC when compared to the UCC (p < .05).ConclusionsThis study provides further evidence that contingency management is effective in promoting abstinence and retention in treatment among individuals with CUD with a history of poor treatment response. Our findings argue for the incorporation of CM among public treatment services for CUD in Brazil.Trial registrationThis study was registered at ClinicalTrials.gov as NCT01815645 on March 21, 2013.

Medications to treat cocaine use disorders: current options.

Cocaine is a highly addictive substance with serious medical and mental health consequences. Despite these concerns, there are no Food and Drug Administration-approved medications for the treatment of cocaine use disorder (CUD). Although many medication-assisted treatments (MATs) have been investigated, no clear guidelines exist for clinicians treating patients with CUDs. There are a limited number of recent data examining MATs for CUD. Multiple high-quality reviews of existing literature have been performed with psychostimulants, modafinil, bupropion, topiramate and disulfiram showing the most promise. Evidence is limited by heterogeneity of studies, small sample sizes and inconsistent results. The current literature does not strongly support any individual MAT for CUD. Psychosocial interventions, namely contingency management, have the most evidence for treatment of CUD, but it is worth seriously considering MAT for patients who do not respond well to psychosocial interventions alone given limitations in access to care, relatively low risks associated with MAT and significant morbidity associated with CUD. Further research into MAT for CUD is necessary, as the combination of MAT and psychosocial interventions may be better than either alone.

Patterns of Cocaine Use During Treatment: Associations With Baseline Characteristics and Follow-Up Functioning

Abstinence outcomes are typically prioritized in the treatment of cocaine use disorder while ignoring patterns of low-frequency cocaine use. This study examined patterns of cocaine use frequency during treatment and evaluated how these patterns related to baseline characteristics and functioning outcomes 6 and 12 months after treatment. We used a pooled dataset (N = 720) from seven randomized clinical trials for cocaine use disorder. The Addiction Severity Index (ASI) was used to assess functioning. Repeated-measures latent class analysis was used to derive patterns of cocaine use. Three patterns were identified: abstinence (10.6%), low-frequency use (approximately 1 day/week; 66.3%), and persistent frequent use (approximately 4 days/week; 23.1%). The low-frequency group was associated with male gender, younger age, and a criminal justice referral. The abstinent group had the highest alcohol problem severity score at baseline. At Month 6, the low-frequency group reported lower problem severity than the persistent frequent use group across multiple ASI areas, including the cocaine use as well as psychological, family, employment, and legal domains. At Month 12, the low-frequency group did not differ from the abstinent group in problem severity on any ASI domain and, relative to the persistent frequent use group, had lower cocaine use and employment problem severity. These findings highlight the importance of adopting a harm reduction approach and recognizing the potential clinical benefits associated with nonabstinent outcomes.

Is Trazodone Contramid Useful in Inducing Patients to Refrain From Using Cocaine After Detoxification, so Avoiding Early Relapse? A Case Series

Objectives: So far, no specific medication has been approved by international drug regulatory agencies for the treatment of cocaine use disorder (CoUD). The reward deficiency syndrome (dysphoric-depressive) was originally described as an outcome after detoxification; it is now considered to be one of the possible routes to relapsing behavior. Materials and Methods: We describe the case of 9 consecutive patients affected by mono CoUD. They voluntarily stopped cocaine use for almost 2 weeks, after daily use for almost 2 months, entering into a dysphoric-depressive syndrome and experiencing a high level of craving for cocaine. All patients received trazodone contramid once a day, at bedtime, at an initial dose of 150 mg the first week, upgraded to 300 mg starting with the second week of treatment; they were followed up for 6 months. Results: Only 1 patient failed to complete 6-month follow-up, relapsing many times into cocaine use during the observational period. Another patient completed the follow-up while improving his psychiatric symptoms but relapsing 3 times into cocaine use. In total, 7/9 patients (77.8%) improved their psychiatric symptoms and, 6 months after starting therapy, remained cocaine-detoxified. Conclusions: The present case series shows that trittico contramid is probably able to positively modify psychopathologic symptomatology and cocaine craving in CoUD patients who voluntarily stopped cocaine use but were at high risk of early relapse. The current need is for controlled clinical trials to confirm the safety and efficacy of trittico contramid in avoiding early relapse in cocaine self-detoxified patients.

Cognitive dysfunction in individuals with cocaine use disorder: Potential moderating factors and pharmacological treatments.

It is well-documented in the literature that individuals repeatedly exposed to cocaine exhibit cognitive impairment and that cognitive dysfunction is a risk factor for poor treatment outcomes in those with cocaine use disorder (CUD). Specific deficits related to attention, episodic memory, working memory, and executive functioning are the most common deficits noted in this population. Given that cognitive impairment is a risk factor for poor treatment outcomes in those with CUD, identifying possible moderating factors contributing to and/or exacerbating cocaine-related cognitive deficits is of great importance. Some of these factors may include premorbid intellectual functioning, cocaine use patterns, polysubstance use, comorbid emotional symptoms, and sleep dysfunction. It is plausible that by identifying moderating factors impacting cognition, behavioral interventions can then be modified accordingly and/or treatment regimens can be augmented with pharmacological interventions (e.g., cognitive enhancing agents), leading to a reduction in treatment attrition and improved treatment outcomes. The currently available treatments for CUD are mainly behavioral with variable efficacy, and even though there have been great preclinical and clinical research efforts focused on medication development for CUD, there are currently no Food and Drug Administration-approved medications for CUD. A description of some of the several potential moderating factors, along with some pharmacological treatments which have been shown to ameliorate, at least to some extent, cognitive dysfunction in those with CUD are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Abuse Potential of Phendimetrazine and its Effects on Cocaine Self‐Administration in Rhesus Monkeys

Cocaine use disorder (CUD) continues to be a major public health and social problem with &gt;1.5 million users resulting in 14,556 deaths in 2017 in the United States and with no FDA‐approved medications available (Volkow and Koob, 2016). Preclinical studies in nonhuman primates have shown that monoamine releasers such as amphetamine can reduce the reinforcing strength of cocaine under several schedules of cocaine self‐administration (SA; Czoty et al. 2010; Negus et al. 2003a, b). However, the high abuse potential of this category of drugs has hindered advancement of their clinical use for treatment of CUD. More recently, preclinical researchers have investigated phendimetrazine (PDM), an FDA‐approved Schedule III anorectic agent, with evidence of efficacy in animal models (Banks and Negus, 2013; Czoty et al. 2016). As a pro‐drug for the monoamine releaser phenmetrazine, PDM has a slow onset and long duration of action. Only two studies (Griffiths et al. 1976; Corwin et al. 1987) have evaluated the reinforcing effects of PDM, with opposite conclusions. The goal of the present study was to compare, in the same subjects, the efficacy of PDM to decrease cocaine SA and the reinforcing strength of PDM relative to cocaine. For 5 consecutive days, three adult male rhesus monkeys responded under a daily fixed‐ratio 20 schedule of food presentation, which, on the fifth day, was followed by a progressive‐ratio (PR) schedule of cocaine (0.003–0.3 mg/kg/injection) presentation (limited hold 30‐min, maximum 4‐hr). PDM was administered daily (1.0–6.0 mg/kg, PO, BID). The primary dependent variable under the PR schedule was the number of injections delivered. Under baseline conditions, monkeys typically earned 10 food reinforcers and the number of cocaine injections was characterized as an inverted U‐shaped function of dose. Under treatment conditions, in two subjects, food‐maintained responding was disrupted at higher PDM doses that also decreased cocaine SA. In the third subject, food reinforcement was not affected and PDM did not show efficacy in decreasing cocaine SA. When PDM (0.1–1.0 mg/kg/injection) was substituted for cocaine, it functioned as a reinforcer in all three subjects; the number of injections observed at peak doses of PDM (0.3 and 1.0 mg/kg/injection) were similar to those observed at the peak dose of cocaine (0.03 mg/kg/injection). These findings suggest that PDM has abuse liability and was ineffective in decreasing cocaine SA. These data do not support the use of PDM as a potential treatment for CUD.Support or Funding InformationP50 DA06634‐27This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Influence of phendimetrazine maintenance on the reinforcing, subjective, performance, and physiological effects of intranasal cocaine.

No pharmacotherapies are approved for cocaine use disorder. Phendimetrazine, a prodrug of the monoamine-releaser phenmetrazine, attenuates the reinforcing effects of cocaine in preclinical models, has minimal abuse potential, and is safe when combined with cocaine. This study determined the influence of phendimetrazine maintenance on the reinforcing effects of cocaine (i.e., choice to self-administer cocaine), along with the subjective, performance, and physiological effects of cocaine. We hypothesized that phendimetrazine would attenuate the reinforcing effects of cocaine. Twenty-nine subjects with cocaine use disorder completed this within-subject, inpatient study. The subjects were maintained on placebo and 210mg phendimetrazine in a counterbalanced order. After at least 7days of maintenance on the target dose, the subjects completed experimental sessions in which the effects of single doses of 0, 20, 40, and 80mg of intranasal cocaine were determined. Cocaine functioned as a reinforcer, producing significant dose-related increases in self-administration. Cocaine increased prototypic effects (e.g., ratings of stimulated and blood pressure). Phendimetrazine attenuated ratings on a select set of subjective outcomes (e.g., ratings of talkative/friendly), but failed to reduce the reinforcing effects of cocaine or a majority of positive subjective cocaine effects. Phendimetrazine increased heart rate, indicating a physiologically active dose was tested, but heart rate increases were not clinically significant. These results indicate that although phendimetrazine can safely be combined with cocaine, it does not attenuate the abuse-related effects of cocaine. It is unlikely, then, that phendimetrazine will be an effective standalone treatment for cocaine use disorder.

Short and long-term improvements in psychiatric symptomatology to validate clinically meaningful treatment outcomes for cocaine use disorders

BackgroundSubstantial efforts have been made to identify clinically meaningful non-abstinence cocaine use outcomes by establishing associations between targeted drug use outcomes and long-term functional improvements. Psychiatric symptomatology is prevalent among those seeking treatment for cocaine use disorder (CUD). Establishing an association between cocaine use outcomes and improvements in psychiatric symptomatology would support clinical validity to these outcome measures. MethodWith data pooled from 5 clinical trials evaluating treatment for CUD (n = 474) multiple linear mixed models were conducted to determine how five specific cocaine use outcome measures performed in terms of improvements in psychiatric symptomatology assessed with the Brief Symptom Inventory (BSI) at baseline, end-of-treatment and 6-month follow-up. ResultsThree outcome measures performed comparably well (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence), in that they consistently predicted improvements in several BSI composite scores at the end-of-treatment and follow-up. The poorer-performing outcome measures were complete abstinence during treatment, percentage of negative urinalysis results and percentage of days abstinent. Improvements in the BSI’s global index of distress, positive symptom total, as well as depression, interpersonal sensitivity, obsessive-compulsion, phobic-anxiety and psychoticism dimensions were consistently associated with outcome effects, while anxiety, hostility, paranoid ideation and somatization were not. ConclusionThe consistent short and long-term association of three outcome measures evaluated here (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence) with improvements psychiatric symptomatology adds support to their clinical relevance as well as their adoption in trials and treatments for CUD.

Effects of chronic cocaine self-administration and N-acetylcysteine on learning, cognitive flexibility, and reinstatement in nonhuman primates

Cocaine use disorder (CUD) is associated with cognitive deficits that have been linked to poor treatment outcomes. An improved understanding of cocaine's deleterious effects on cognition may help optimize pharmacotherapies. Emerging evidence implicates abnormalities in glutamate neurotransmission in CUD and drugs that normalize glutamatergic homeostasis (e.g., N-acetylcysteine [NAC]) may attenuate CUD-related relapse behavior. The present studies examined the impact of chronic cocaine exposure on touchscreen-based models of learning (repeated acquisition) and cognitive flexibility (discrimination reversal) and, also, the ability of NAC to modulate cocaine self-administration and its capacity to reinstate drug-seeking behavior. First, stable repeated acquisition and discrimination reversal performance was established. Next, high levels of cocaine-taking behavior (2.13-3.03mg/kg/session) were maintained for 150 sessions during which repeated acquisition and discrimination reversal performance was probed periodically. Finally, the effects of NAC treatment were examined on cocaine self-administration and, subsequently, extinction and reinstatement. Cocaine self-administration significantly impaired performance under both cognitive tasks; however, discrimination reversal was disrupted considerably more than acquisition. Performance eventually approximated baseline levels during chronic exposure. NAC treatment did not perturb ongoing self-administration behavior but was associated with significantly quicker extinction of drug-lever responding. Cocaine-primed reinstatement did not significantly differ between groups. The disruptive effects of cocaine on learning and cognitive flexibility are profound but performance recovered during chronic exposure. Although the effects of NAC on models of drug-taking and drug-seeking behavior in monkeys are less robust than reported in rodents, they nevertheless suggest a role for glutamatergic modulators in CUD treatment programs.

Translating the atypical dopamine uptake inhibitor hypothesis toward therapeutics for treatment of psychostimulant use disorders.

Medication-assisted treatments are unavailable to patients with cocaine use disorders. Efforts to develop potential pharmacotherapies have led to the identification of a promising lead molecule, JJC8-091, that demonstrates a novel binding mode at the dopamine transporter (DAT). Here, JJC8-091 and a structural analogue, JJC8-088, were extensively and comparatively assessed to elucidate neurochemical correlates to their divergent behavioral profiles. Despite sharing significant structural similarity, JJC8-088 was more cocaine-like, increasing extracellular DA concentrations in the nucleus accumbens shell (NAS) efficaciously and more potently than JJC8-091. In contrast, JJC8-091 was not self-administered and was effective in blocking cocaine-induced reinstatement to drug seeking. Electrophysiology experiments confirmed that JJC8-091 was more effective than JJC8-088 at inhibiting cocaine-mediated enhancement of DA neurotransmission. Further, when VTA DA neurons in DAT-cre mice were optically stimulated, JJC8-088 produced a significant leftward shift in the stimulation-response curve, similar to cocaine, while JJC8-091 shifted the curve downward, suggesting attenuation of DA-mediated brain reward. Computational models predicted that JJC8-088 binds in an outward facing conformation of DAT, similar to cocaine. Conversely, JJC8-091 steers DAT towards a more occluded conformation. Collectively, these data reveal the underlying molecular mechanism at DAT that may be leveraged to rationally optimize leads for the treatment of cocaine use disorders, with JJC8-091 representing a compelling candidate for development.

Topiramate Might Help a Subgroup of People with Cocaine Use Disorder

Results from studies of medications for treating cocaine use disorder (CUD) have been largely disappointing, but targeting particular subtypes might

Preliminary evidence for accelerated intermittent theta-burst stimulation as a treatment for cocaine use disorder

Preliminary evidence for accelerated intermittent theta-burst stimulation as a treatment for cocaine use disorder

TMS in treatment of Cocaine Use Disorder

Cocaine exerts its physiological effects through the accumulation of neurotransmitters, particularly dopamine, in the neuronal synaptic cleft. The euphoria associated with cocaine use results from enhanced and prolonged dopaminergic activity in the mesolimbic system, our reward pathway. Cocaine is an illicit stimulant that has similar effects to amphetamine and amphetamine-type stimulants. Therefore, the criteria for diagnosis of cocaine use disorder (CUD) falls under the broader umbrella of Stimulant Use Disorder (SUD). Overall, SUD or commonly, “addiction”, can be described as a persistent state of reduced cognitive capacity to control compulsive drug-seeking behavior, despite the risk of negative consequences. The primary treatment options for these disorders includes psychosocial and behavioral interventions. Though several drugs have been trialed, there is no pharmacological substitute treatment for patients dependent on cocaine or other CNS stimulants. Transcranial magnetic stimulation (TMS) is an emerging treatment modality. TMS is a non-invasive brain stimulation technique that affects cortical excitability and causes a release of dopamine in the mesolimbic system, enabling modulation of neuronal networks that are important for behavior and cognition. While TMS is approved by US FDA and in Europe (CE) for Major Depressive Disorder, TMS is not approved anywhere for treatment of addiction. The use of MagVenture TMS Therapy (MagPro, MagVita) devices for applications outside the approved intended use in a given country is the responsibility of the researchers performing this study. To date, a total of 6 pilot studies testing the effect of TMS for treatment of CUD are published. Cumulatively, the studies demonstrate that stimulation of the left prefrontal cortex with high frequency TMS may be an encouraging treatment opportunity for CUD in reducing intake and craving of cocaine.

Transcranial direct current stimulation in cocaine use disorders: preliminary findings

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive, well tollerated, simple to use neuromodulation technique. Recently its application on the dorsolateral prefrontal cortex (DLPFC) was reported to be a possible tool to reduce craving in substance use disorders. [1,2]. In this double blind sham-controlled study we aimed to evaluate the efficacy of tDCS in the treatment of Cocaine Use Disorder (CUD) an its potential impact on depressive and impulsivity dimensions. [3]

Abstract #157: Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices reduces Cocaine Self-Administration

Introduction: Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD.

Sleep quality in patients with cocaine use disorder undergoing repetitive Transcranial Magnetic Stimulation (rTMS)

Background. Sleep disturbance is a prominent and common complaint in people with cocaine use disorder (CUD), either during use or withdrawal. Repetitive transcranial magnetic stimulation (rTMS) has shown promise used as a treatment for CUD.

Impulsiveness as a predictor of topiramate response for cocaine use disorder.

Topiramate has been studied in the treatment of substance use disorders and is often used off-label in the treatment of other disorders with impaired impulse control. We sought to determine whether impulsiveness could predict topiramate treatment response in individuals with cocaine use disorder (CUD). In a post-hoc analysis of a 12-week, double-blind, randomized, placebo-controlled trial of topiramate for CUD, we examined the relationship between response to treatment and participants' baseline score on the Barrett Impulsiveness Scale (BIS-11). During the original trial, topiramate was titrated up to 300 mg/day over 6 weeks and maintained for 6 weeks. All participants received weekly cognitive behavioral therapy. Individuals with total BIS-11 scores above the median had 11.2% more cocaine-free days with topiramate versus placebo (Bonferroni corrected p = 0.047). Individuals with first-order factor scores above the median in self-control (Bonferroni corrected p = 0.020) and at or below the median in attention (Bonferroni corrected p = 0.022), and second-order factor scores at or below the median in attentional (Bonferroni corrected p = 0.024) and motor impulsiveness (Bonferroni corrected p = 0.046) were all associated with a greater improvement with topiramate. The results indicate an association between higher within-group impulsiveness and response to topiramate for CUD. The subscore findings may suggest a complex interaction between effectiveness and known cognitive side effects. The finding that trait impulsiveness is associated with treatment response is a promising discovery that may help guide treatment for CUD. This analysis suggests a possible endophenotype based on impulsiveness that can predict treatment response to topiramate. (Am J Addict 2019;XX:1-6).

Connectome-Based Prediction of Cocaine Abstinence.

The authors sought to identify a brain-based predictor of cocaine abstinence by using connectome-based predictive modeling (CPM), a recently developed machine learning approach. CPM is a predictive tool and a method of identifying networks that underlie specific behaviors ("neural fingerprints"). Fifty-three individuals participated in neuroimaging protocols at the start of treatment for cocaine use disorder, and again at the end of 12 weeks of treatment. CPM with leave-one-out cross-validation was conducted to identify pretreatment networks that predicted abstinence (percent cocaine-negative urine samples during treatment). Networks were applied to posttreatment functional MRI data to assess changes over time and ability to predict abstinence during follow-up. The predictive ability of identified networks was then tested in a separate, heterogeneous sample of individuals who underwent scanning before treatment for cocaine use disorder (N=45). CPM predicted abstinence during treatment, as indicated by a significant correspondence between predicted and actual abstinence values (r=0.42, df=52). Identified networks included connections within and between canonical networks implicated in cognitive/executive control (frontoparietal, medial frontal) and in reward responsiveness (subcortical, salience, motor/sensory). Connectivity strength did not change with treatment, and strength at posttreatment assessment also significantly predicted abstinence during follow-up (r=0.34, df=39). Network strength in the independent sample predicted treatment response with 64% accuracy by itself and 71% accuracy when combined with baseline cocaine use. These data demonstrate that individual differences in large-scale neural networks contribute to variability in treatment outcomes for cocaine use disorder, and they identify specific abstinence networks that may be targeted in novel interventions.