Treatment Of Cocaine Use Disorder Research Articles

Examination of preliminary behavioral and effective connectivity findings from treatment response to citalopram in cocaine use disorder: A dynamic causal modeling study

We sought effective (directional) connectivity parameters associated with response to citalopram in cocaine use disorder (CUD) by conducting a functional magnetic resonance imaging (fMRI) experiment with participants diagnosed with CUD (n = 13) and matched healthy controls (HC; n = 17). CUD participants showed a positive correlation between bilateral DLPFC-to-putamen effective connectivity and treatment effectiveness score. These preliminary results support further investigation of prefrontal-striatal interactions in response to treatment in CUD.

Long-term Changes in the Central Amygdala Proteome in Rats with a History of Chronic Cocaine Self-administration

The central nucleus of the amygdala (CeA) is a striatum-like structure that contains mainly inhibitory circuits controlling a repertoire of (mal)adaptive behaviors related to pain, anxiety, motivation, and addiction. Neural activity in the CeA is also necessary for the expression of persistent and robust drug seeking, also termed ‘incubation of drug craving.’ However, neuroadaptations within this brain region supporting incubated drug craving have not been characterized. Here, we conducted a comprehensive analysis of protein expression in the CeA of male rats after prolonged (45-day) abstinence from extended-access cocaine self-administration using a quantitative proteomic approach. The proteomic analysis identified 228 unique proteins altered in cocaine rats relative to animals that received saline. Out of the identified proteins, 160 were downregulated, while 68 upregulated. Upregulation of tyrosine hydroxylase and downregulation of neural cell-adhesion protein contactin-1 were validated by immunoblotting. Follow-up analysis by the Ingenuity Pathway Analysis tool revealed alterations in protein networks associated with several neurobehavioral disorders, cellular function and morphology, as well as axogenesis, long-term potentiation, and receptor signaling pathways. This study suggests that chronic cocaine self-administration, followed by a prolonged abstinence results in reorganization of specific protein signaling networks within the CeA that may underlie incubated cocaine craving and identifies potential novel ‘druggable’ targets for the treatment of cocaine use disorder (CUD).

Impulsiveness as a moderator of amphetamine treatment response for cocaine use disorder among ADHD patients

BackgroundAmphetamines are a first-line treatment for ADHD and have shown promise for the treatment of cocaine use disorder (CUD), both alone and with comorbid ADHD. Impulsiveness is a key aspect of both ADHD and substance use disorders. We sought to understand the role of baseline impulsiveness in the treatment of comorbid CUD and ADHD. MethodsIn a post hoc analysis (N = 76) of a 14-week, double-blind, randomized, placebo-controlled trial of mixed amphetamine salts-extended release (MAS-ER) for comorbid ADHD and CUD, we examined the relationship between treatment response and participants’ baseline Barratt Impulsiveness Scale (BIS-11) score by comparing those with scores below versus above the median. In the original trial, participants received daily 60 mg MAS-ER, 80 mg MAS-ER, or placebo, in conjunction with cognitive behavioral therapy. ResultsThe odds of a cocaine-abstinent week over time were significantly greater in the high BIS group compared to the low BIS group, both when missing data was treated as missing (p = .0155; OR = 1.23, 95% CI: 1.13, 1.35 versus OR = 1.04, 95% CI: 0.95, 1.15) and when missing data was treated as cocaine-positive (p = .003; OR = 1.15, 95% CI: 1.06, 1.24 versus OR = 0.96, 95% CI: 0.88, 1.05). ConclusionsThe results show an association between higher within-group trait impulsiveness, as measured by the BIS-11, and response to MAS-ER for CUD in a cohort with comorbid ADHD. This result further demonstrates that impulsiveness is an important factor when considering treatment options for patients with CUD and that higher baseline impulsiveness may predict response to treatment with psychostimulants for CUD.

A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Sleep quality improves during treatment with repetitive transcranial magnetic stimulation (rTMS) in patients with cocaine use disorder: a retrospective observational study

BackgroundSleep disturbance is a prominent and common complaint in people with cocaine use disorder (CUD), either during intake or withdrawal. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a treatment for CUD. Thus, we evaluated the relationship between self-perceived sleep quality and cocaine use pattern variables in outpatients with CUD undergoing an rTMS protocol targeted at the left dorsolateral prefrontal cortex.MethodsThis is a retrospective observational study including 87 patients diagnosed with CUD according to the DSM-5 criteria. Scores in Pittsburgh Sleep Quality Index (PSQI), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist 90-Revised (outcome used: Global Severity Index, GSI) were recorded at baseline, and after 5, 30, 60, and 90 days of rTMS treatment. Cocaine use was assessed by self-report and regular urine screens.ResultsSleep disturbances (PSQI scores > 5) were common in patients at baseline (mean ± SD; PSQI score baseline: 9.24 ± 3.89; PSQI > 5 in 88.5% of patients). PSQI scores significantly improved after rTMS treatment (PSQI score Day 90: 6.12 ± 3.32). Significant and consistent improvements were also seen in craving and in negative-affect symptoms compared to baseline. Considering the lack of a control group, in order to help the conceptualization of the outcomes, we compared the results to a wait-list group (n = 10). No significant improvements were observed in the wait-list group in any of the outcome measures.ConclusionsThe present findings support the therapeutic role of rTMS interventions for reducing cocaine use and accompanying symptoms such as sleep disturbance and negative-affect symptoms.Trial registrationClinicalTrials.gov.NCT03733821.

Beta‐caryophyllene, a Volatile Phytocannabinoid, Attenuates Cocaine Self‐administration and Relapse in Rats

Cocaine abuse continues to be a serious health problem worldwide. Despite intense research, there is still no FDA‐approved medication to treat cocaine use disorder. The recent search for effective therapeutics has been focused on the endocannabinoid system because of its critical role in the neurobiology of drug addiction. In the last decade, there has been a growing interest in beta‐caryophyllene (BCP), a volatile phytocannabinoid present in high proportions in cannabis and large number of spice and food plants including black pepper, thyme and cloves. This dietary additive that has a CB2 receptor (CB2R) agonist profile, has shown to produce promising therapeutic effects for multiple neuropsychiatric disorders. Surprisingly, the therapeutic potential of BCP in the treatment of drug abuse and addiction has not been explored. Here, using gold standard animal models of drug abuse, we systematically evaluated the potential utility of BCP against cocaine‐related behaviors in rodents and its mechanisms of action. In a series of experiments we found that BCP attenuated cocaine‐enhanced electrical brain‐stimulation reward and optogenetic intracranial self‐stimulation driven by activation of dopamine (DA) neurons in DAT‐cre mice, both outcomes indicating reduced reward. Intriguingly, when administered systemically or orally, BCP attenuated cocaine self‐administration in rats, suggesting an ability to reduce drug abuse. BCP also reduced drug‐primed reinstatement of cocaine seeking and cocaine conditioned place preference, indicative of its preventative effects against relapse. When BCP was substituted for cocaine, rats ceased responding, suggesting BCP has low liability abuse. In regards to the receptor mechanisms, our pharmacological approach (along with our transgenic approach utilizing with CB1, CB2, GPR55 knockout mice) indicates that BCP produces attenuating effects on cocaine self‐administration that are mediated by non‐cannabinoid receptors. We are now exploring the involvement of peroxisome proliferator‐activated receptor (PPAR) and transient receptor potential vanilloid 1 cation channels (TRPV1) in BCP action against cocaine. Our findings suggest that BCP shows exceptional promise as a therapeutic candidate in the treatment of cocaine use disorder. Importantly, given its good oral bioavailability and the advantage of being an already FDA‐approved non‐toxic dietary additive, BCP is a valuable candidate for drug repurposing programs in translational medicine.

Stressing the potential of guanfacine as a treatment for cocaine use disorder.

Stressing the potential of guanfacine as a treatment for cocaine use disorder.

Benefits of Therapy With Virtual Reality Exposure in the Treatment of Cocaine Use Disorders

Benefits of Therapy With Virtual Reality Exposure in the Treatment of Cocaine Use Disorders

Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant

ABSTRACTBackground: The α1 antagonist doxazosin reduces cocaine use in individuals with cocaine use disorder (CUD) through a functional polymorphism of the α1 adrenoreceptor. The regulatory role of the α1 adrenoreceptor subtype D (ADRA1D) gene polymorphism in CUD is uncharacterized.Objectives: To study how the genetic variant of ADRA1D gene (T1848A, rs2236554) may affect the treatment efficacy of doxazosin in reducing cocaine use.Methods: This 12-week pilot trial included 76 participants with CUD with ADRA1D (T1848A, rs2236554) AA (N = 40) or AT/TT genotype (N = 36). Participants were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29), and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy.Results: The AA and the AT/TT groups had comparable baseline rates of cocaine positive urines at weeks 1–2 (~ 76%). In the placebo group, an increase of cocaine positive urines in the AT/TT group was found as compared to the AA group (24% vs. 9%). In the doxazosin group, a greater decrease in cocaine positive urines was found in the AT/TT group relative to the AA group. The difference between the doxazosin and placebo groups in cocaine negative urines became evident at weeks 5–6 and peaked at weeks 9–10 (~35% difference). The AT/TT group demonstrated a significant medication and time by medication effect (p < .001), whereas the AA group did not.Conclusion: The T-allele carriers showed a greater reduction of cocaine use after treatment with doxazosin in participants with the ADRA1D gene polymorphism (T1848A), suggesting that this SNP may serve as a pharmacogenetic marker in pharmacotherapy of CUD.

Combined Topiramate and Mixed Amphetamine Salts for Cocaine Use Disorder

Prescribed stimulants and topiramate have had mixed results in treating cocaine use disorder (CUD). Individuals with higher impulsivity may be

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study.

There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.

The treatment of cocaine use disorder.

Cocaine use continues to be a serious worldwide public health problem. Cocaine abuse is associated with substantial morbidity and mortality. Cocaine overdose deaths are increasing in the United States and, in certain populations, outnumber heroin and opiate overdose deaths. Psychosocial treatments remain the treatments of choice for cocaine use disorder (CUD), with standard approaches including contingency management and cognitive behavioral therapy. However, the effect sizes of these treatments are not large, and they are not effective for most patients. Consequently, investigators have sought to develop pharmacological agents to augment the efficacy of psychosocial treatments. Despite these efforts, no medications have yet been proven to be safe and effective for the treatment of CUD. The most promising pharmacological strategies for CUD treatment thus far include the use of dopamine agonists, such as long-acting amphetamine and modafinil or glutamatergic and GABAergic agents such as topiramate. Combination drugs may be especially promising.

Remarkable Reduction of Cocaine Use in Dual Disorder (Adult Attention Deficit Hyperactive Disorder/Cocaine Use Disorder) Patients Treated with Medications for ADHD.

Background: Cocaine use disorder (CUD) is a growing public health concern, but so far no effective pharmacotherapies have been demonstrated. Stimulant medications have proved to be promising in CUD treatment. The self-medication hypothesis (SMH) can help to explain this phenomenon better, especially in cases where CUD co-occurs with adult attention deficit hyperactivity disorder (A-ADHD). Methods: In the present retrospective study, a sample of 20 consecutive patients (aged from 18 to 65 years) with dual disorder (A-ADHD/CUD), under treatment with methylphenidate (MPH) or atomoxetine (ATM) medications, was followed to study the effects of A-ADHD treatment on cocaine use. Patients were followed for a mean period of 7 months (minimum 1, maximum 30 months). All individuals were assessed with standardized questionnaires to evaluate diagnosis, treatment efficacy, and clinical improvement. Results: the results showed that behaviors reflecting cocaine addiction were sharply reduced during the stimulant treatment of A-ADHD, and were not correlated with age, gender, familiarity, length of treatment, or medication used. CUD improvement was closely correlated with the A-ADHD improvement. This study supports the validity of the SMH in ADHD patients with co-occurring CUD.

Change in employment status and cocaine use treatment outcomes: A secondary analysis across six clinical trials

BackgroundUnemployment is a chronic problem among treatment seeking substance users and is associated with poor treatment response. Most studies that have examined the relationship between employment and treatment outcomes for substance use disorders have done so by considering employment at only one specific point in time (e.g., upon entering treatment). There is a lack of research on how change in employment status over time is associated with substance use treatment outcomes. The aim of this study was to evaluate both static employment status and change in employment status over time as predictors of cocaine use treatment outcomes. MethodsWe utilized data pooled from six randomized clinical trials evaluating treatment for cocaine use disorders (n = 553). Multiple general linear mixed models were conducted to determine the association of baseline, end-of-treatment, and change in employment status (from baseline to end-of-treatment) with treatment outcomes. ResultsTreatment outcomes did not differ by baseline employment status but were significantly better for those employed versus unemployed at the end-of-treatment. In regard to change in employment status over time, those who were unemployed at baseline and acquired employment by end-of-treatment had significantly better treatment outcomes during active treatment and follow-up, as compared to those who were unemployed at baseline and remained unemployed by end-of-treatment. ConclusionOur findings suggest that end-of-treatment employment status may be an important marker of good outcome among those unemployed at treatment entry and support the incorporation of interventions designed to promote employment by substance use disorders treatment programs.

Sociodemographic and clinical outcome differences among individuals seeking treatment for cocaine use disorders. The intersection of gender and race

BackgroundMost published treatment trials for cocaine use disorders (CUD) have been conducted with samples composed predominantly of White men and underrepresent women and racial/ethnic minorities. Because of the high prevalence of men and White individuals in CUD treatment trials, results from studies that have compared treatment outcomes by gender and race or ethnicity separately may not be representative of women or racial/ethnic minorities. MethodsWith a sample pooled from seven randomized clinical trials of treatment for CUD (n = 629), baseline characteristics and treatment outcome responses were compared with 4 subgroups of individuals created based on the intersection of gender and race (White men, Black men, White women and Black women). ResultsAt baseline, sociodemographic status, pattern, frequency and severity of cocaine use, psychiatric comorbidities, employment and legal problems significantly differed across groups. Treatment outcome indicators collected during treatment and through follow-up, consistently indicated poorer outcomes among the sample of White women, but were similar for the other groups. ConclusionsMen and women with CUD from both racial groups enter treatment with different psychosocial issues (e.g., history of violence/trauma, financial problems, co-occurring psychiatric disorders) and substance use problems (e.g. types of substances) that may impact treatment outcomes and indicate a need for culturally-informed care to deliver more effective treatment for CUD. Poorer overall outcomes among White women may reflect the need for a more focused treatment approach for this group; and highlight the importance of evaluating gender and race in treatment trials to better address health disparities.

Activation of GSK3β induced by recall of cocaine reward memories is dependent on GluN2A/B NMDA receptor signaling

Glycogen synthase kinase-3β (GSK3β) is a critical regulator of the balance between long-term depression and long-term potentiation which is essential for learning and memory. Our previous study demonstrated that GSK3β activity is highly induced during cocaine memory reactivation, and that reconsolidation of cocaine reward memory is attenuated by inhibition of GSK3β. NMDA receptors and protein phosphatase 1 (PP1) are activators of GSK3β. Thus, this study investigated the roles of NMDA receptor subtypes and PP1in the reconsolidation of cocaine contextual reward memory. Cocaine contextual memories were established and evaluated using cocaine conditioned place preference methods. The regulation of GSK3β activity in specific brain areas was assessed by measuring its phosphorylation state using immunoblot assays. Mice underwent cocaine place conditioning for 8days and were tested for place preference on day 9. Twenty-four hours later, mice were briefly confined to the compartment previous paired with cocaine to reactivate cocaine-associated memories. Administration of the GluN2A- and GluN2B-NMDA receptor antagonists, NVP-AAM077 and ifenprodil, respectively, immediately following recall abrogated an established cocaine place preference, while preventing the activation of GSK3β in the amygdala, nucleus accumbens, and hippocampus during cocaine memory reactivation. PP1 inhibition with okadaic acid also blocked the activation of GSK3β and attenuated a previously established cocaine place preference. These findings suggest that the dephosphorylation of GSK3β that occurred upon activation of cocaine-associated reward memories may be initiated by the activation of PP1 during the induction of NMDA receptor-dependent reconsolidation of cocaine mnemonic traces. Moreover, the importance of NMDA receptors and PP1 in reconsolidation of cocaine memory makes them potential therapeutic targets in treatment of cocaine use disorder and prevention of relapse.

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.