Predictors of cocaine use disorder treatment outcomes: a systematic review.

BACKGROUND: Psychosocial approaches are the first-line treatments for cocaine dependence, although they still present high dropout and relapse rates. Thus, there is a pressing need to understand which variables influence treatment outcomes to improve current treatments and prevent dropout and relapse rates. The aim of this study is to explore predictors of treatment retention and abstinence in CUD. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched three databases-PubMed, PsychINFO and Web of Science-for randomized clinical trials (RCTs) published in English and Spanish from database inception through April 1, 2023. We selected all studies that met the inclusion criteria (adults aged ≥ 18, outpatient treatment, CUD as main addiction, and no severe mental illness) to obtain data for the narrative synthesis addressing cocaine abstinence and treatment retention as main outcome variables. After data extraction was completed, risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB-2). RESULTS: A total of 566 studies were screened, and, of those, 32 RCTs were included in the synthesis. Younger age, more years of cocaine use, and craving levels were significant predictors of relapse and treatment dropout. Fewer withdrawal symptoms, greater baseline abstinence, greater treatment engagement, and more self-efficacy were all predictors of longer duration of abstinence. The role of impulsivity as a predictor of CUD is unclear due to conflicting data, although the evidence generally suggests that higher impulsivity scores can predict more severe addiction and withdrawal symptoms, and earlier discontinuation of treatment. CONCLUSION: Current evidence indicates which variables have a direct influence on treatment outcomes, including well-studied cocaine use-related variables. However, additional variables, such as genetic markers, appear to have a high impact on treatment outcomes and need further study. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered at PROSPERO (ID: CRD42021271847). This study was funded by the Spanish Ministry of Science, Innovation and Universities, Instituto Carlos III (ISCIII) (FIS PI20/00929) and FEDER funds and Fundació Privada Hospital de la Santa Creu i Sant Pau (Pla d'acció social 2020).

The Mexican dataset of a repetitive transcranial magnetic stimulation clinical trial on cocaine use disorder patients: SUDMEX TMS.

Cocaine use disorder (CUD) is a global health problem with severe consequences, leading to behavioral, cognitive, and neurobiological disturbances. While consensus on treatments is still ongoing, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach for medication-resistant disorders, including substance use disorders. In this context, here we present the SUDMEX-TMS, a Mexican dataset from an rTMS clinical trial involving CUD patients. This longitudinal dataset comprises 54 CUD patients (including 8 females) with data collected at five time points: baseline (T0), two weeks (T1), three months (T2), six months (T3) follow-up, and twelve months (T4) follow-up. The clinical rTMS treatment followed a double-blinded randomized clinical trial design (n = 24 sham/30 active) for 2 weeks, followed by an open-label phase. The dataset includes demographic, clinical, and cognitive measures, as well as magnetic resonance imaging (MRI) data collected at all time points, encompassing structural (T1-weighted), functional (resting-state fMRI), and multishell diffusion-weighted (DWI-HARDI) sequences. This dataset offers the opportunity to investigate the impact of rTMS on CUD participants, considering clinical, cognitive, and multimodal MRI metrics in a longitudinal framework.

Examining predictors of cocaine withdrawal syndrome at the end of detoxification treatment in women with cocaine use disorder.

BACKGROUND: Detoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification. METHODS: Data from 284 women with CUD who enrolled in a 3-week detoxification program was used in this longitudinal study. Psychosocial, clinical, and drug use behavior characteristics were evaluated, generating a dataset with 256 potential predictors. We tested six different machine learning classification algorithms. RESULTS: The best classification algorithm achieved an average accuracy and ROC-AUC of approximately 70%. The 16 features selected as best predictors were the severity of psychiatric, family, and social problems and the level of exposure to childhood maltreatment. Features associated with drug-use behavior included days consuming drugs and having craving symptoms in the last month before treatment, number of previous drug/alcohol-related treatments, and a composite score of addiction severity. The level of cocaine withdrawal syndrome at the beginning of detoxification was also a key feature for classification. A network analysis revealed the pattern of association between predictors. CONCLUSION: These variables can be assessed in real-world clinical settings, potentially helping clinicians to identify individuals with severe cocaine withdrawal that is likely to be sustained over the course of detoxification.

Cocaine abstinence during the "critical period" of a contingency management trial predicts future abstinence in people with cocaine use disorder.

BACKGROUND: Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this "critical period" has not been reported in CM trials. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period. METHODS: Eighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results. RESULTS: Participants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period. CONCLUSIONS: These results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers.

Effects of transcranial magnetic stimulation on cocaine addiction: A systematic review of randomized controlled trials.

OBJECTIVE: While pharmacological strategies appear to be ineffective in treating long-term addiction, repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. METHOD: A systematic review of randomized controlled trials (RCTs) was conducted on the efficacy and tolerability of rTMS in treating cocaine use disorder (CUD). Relevant papers published in English through November 30th 2022 were identified, searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Eight studies matched inclusion criteria. The best findings were reported by the RCTs conducted at high-frequency (≥5 Hz) multiple sessions of rTMS delivered over the left dorsolateral prefrontal cortex (DLPFC): a significant decrease in self-reported cue-induced cocaine craving and lower cocaine craving scores and a considerable amelioration in the tendency to act rashly under extreme negative emotions (impulsivity) were found in the active group compared to controls. CONCLUSION: Although still scant and heterogeneous, the strongest evidence so far on the use of rTMS on individuals with CUD support the high frequency stimulation over the left DLPFC as a well tolerated treatment of cocaine craving and impulsivity.

Integrative data analysis of clinical trials network studies to examine the impact of psychosocial treatments for black people who use cocaine: Study protocol.

BACKGROUND: Cocaine overdose death rates among Black people are higher than that of any other racial/ethnic group, attributable to synthetic opioids in the cocaine supply. Understanding the most effective psychostimulant use treatment interventions for Black people is a high priority. While some interventions have proven effective for the general population, their comparative effectiveness among Black people remains unknown. To address this gap, our NIDA-funded Clinical Trials Network (CTN) study (0125), will use Integrative Data Analysis (IDA) to examine treatment effectiveness across 9 CTN studies. This manuscript describes the study protocol for CTN-0125. METHODS: Of the 59 completed randomized clinical trials in the CTN with available datasets, nine met our inclusion criteria: 1) behavioral intervention, 2) targeted cocaine use or use disorder, 3) included sub-samples of participants who self-identified as Black and 4) included outcome measures of cocaine and psychostimulant use and consequences. We aim to 1) estimate scale scores of cocaine use severity while considering study-level measurement non-invariance, 2) compare the effectiveness of psychosocial treatments for psychostimulant use, and 3) explore individual (e.g., concomitant opioid use, age, sex, employment, pre-treatment psychiatric status) and study-level moderators (e.g., attendance/retention) to evaluate subgroup differences in treatment effectiveness. CONCLUSION: The NIDA CTN provides a unique collection of studies that can offer insight into what interventions are most efficacious for Black people. Findings from our CTN-0125 study have the potential to substantially inform treatment approaches specifically designed for Black people who use psychostimulants.

Distinct neural networks predict cocaine versus cannabis treatment outcomes.

Treatment outcomes for individuals with substance use disorders (SUDs) are variable and more individualized approaches may be needed. Cross-validated, machine-learning methods are well-suited for probing neural mechanisms of treatment outcomes. Our prior work applied one such approach, connectome-based predictive modeling (CPM), to identify dissociable and substance-specific neural networks of cocaine and opioid abstinence. In Study 1, we aimed to replicate and extend prior work by testing the predictive ability of the cocaine network in an independent sample of 43 participants from a trial of cognitive-behavioral therapy for SUD, and evaluating its ability to predict cannabis abstinence. In Study 2, CPM was applied to identify an independent cannabis abstinence network. Additional participants were identified for a combined sample of 33 with cannabis-use disorder. Participants underwent fMRI scanning before and after treatment. Additional samples of 53 individuals with co-occurring cocaine and opioid-use disorders and 38 comparison subjects were used to assess substance specificity and network strength relative to participants without SUDs. Results demonstrated a second external replication of the cocaine network predicting future cocaine abstinence, however it did not generalize to cannabis abstinence. An independent CPM identified a novel cannabis abstinence network, which was (i) anatomically distinct from the cocaine network, (ii) specific for predicting cannabis abstinence, and for which (iii) network strength was significantly stronger in treatment responders relative to control particpants. Results provide further evidence for substance specificity of neural predictors of abstinence and provide insight into neural mechanisms of successful cannabis treatment, thereby identifying novel treatment targets. Clinical trials registation: "Computer-based training in cognitive-behavioral therapy web-based (Man VS Machine)", registration number: NCT01442597 . "Maximizing the Efficacy of Cognitive Behavior Therapy and Contingency Management", registration number: NCT00350649 . "Computer-Based Training in Cognitive Behavior Therapy (CBT4CBT)", registration number: NCT01406899 .

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors.

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate model.

A promising strategy for cocaine addiction treatment is the anti-drug vaccine. These vaccines induce the production of anticocaine antibodies, capable of linking to cocaine, and decrease the passage of cocaine throughout the blood-brain barrier, decreasing drug activity in the brain. Our research group developed a new vaccine candidate, the UFMG-V4N2, to treat cocaine use disorders (CUD) using an innovative carrier based on calixarenes. This study assessed the safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate toxicity study using single and multiple vaccine doses. The UFMG-VAC-V4N2 yielded only mild effects in the injection site and did not influence the general health, feeding behavior, or hematological, renal, hepatic, or metabolic parameters in the vaccinated marmosets. The anti-cocaine vaccine UFMG-VAC-V4N2 presented a favorable safety profile and induced the expected immune response in a non-human primate model of Callithrix penicillata. This preclinical UFMG-VAC-V4N2 study responds to the criteria required by international regulatory agencies contributing to future anticocaine clinical trials of this anti-cocaine vaccine.

Assessing cocaine motivational value: Comparison of brain reactivity bias toward cocaine cues and cocaine demand.

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q0, essential value [EV], Omax, Pmax, and breakpoint [BP]) were evaluated via Bayesian generalized linear modeling. Positive associations (posterior probabilities ≥ 75%) were found between LPP amplitude and four demand indices (Q0, EV, Omax, BP). These results suggest that individuals who attach greater relevance to cocaine cues also exhibit greater valuation of cocaine reward. Implications for incorporating methodology from behavioral science and brain imaging are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Trends in cannabis or cocaine-related dependence and alcohol/drug treatment in Argentina, Chile, and Uruguay.

BACKGROUND: In the context of changing cannabis and other drug policy and regulation, concerns may arise regarding drug treatment access and use. We assessed cannabis/cocaine-related dependence and treatment in Argentina, Chile, and Uruguay. METHODS: Nationally representative cross-sectional household surveys of people ages 15-64 in Argentina (4 surveys, 2006-2017), Chile (7 surveys, 2006-2018), and Uruguay (4 surveys, 2006-2018) were harmonized. We estimated weighted prevalences of cannabis or cocaine-related (cocaine or cocaine paste) dependence, based on meeting 3+ past-year ICD-10 dependence criteria. We estimated weighted prevalences of past-year alcohol/drug treatment use (Argentina, Chile) or use/seeking (Uruguay) among people with past-year cannabis/cocaine-related dependence. We tested model-based prevalence trends over time and described individual-level treatment correlates by country. RESULTS: Cannabis/cocaine dependence prevalence increased in the region starting in 2010-2011, driven by cannabis dependence. Adjusted cannabis dependence prevalence increased from 0.7% in 2010 to 1.5% in 2017 in Argentina (aPD=0.8, 95% CI= 0.3, 1.2), from 0.8% in 2010 to 2.8% in 2018 in Chile (aPD=2.0, 95% CI= 1.4, 2.6), and from 1.4% in 2011 to 2.4% in 2018 in Uruguay (aPD=0.9, 95% CI= 0.2, 1.6). Cocaine-related dependence increased in Uruguay, decreased in Argentina, and remained stable in Chile. Among people with past-year cannabis/cocaine dependence, average alcohol/drug treatment use prevalence was 15.3% in Argentina and 6.0% in Chile, while treatment use/seeking was 14.7% in Uruguay. Alcohol/drug treatment prevalence was lower among people with cannabis dependence than cocaine-related dependence. Treatment correlates included older ages in all countries and male sex in Argentina only. CONCLUSION: Alcohol/drug treatment use among people with cannabis/cocaine-related dependence remained low, signaling an ongoing treatment gap in the context of growing cannabis dependence prevalence in the region. Additional resources may be needed to increase treatment access and uptake. Future studies should assess contributors of low treatment use, including perceived need, stigma, and service availability.

A preliminary investigation of schedule parameters on cocaine abstinence in contingency management.

Contingency management (CM) interventions are the most effective psychosocial interventions for substance use disorders. However, further investigation is needed to create the most robust intervention possible. This study investigated the effects of 1) reinforcer magnitude; and 2) fixed and escalating and resetting incentives on cocaine abstinence in an outpatient trial. In this analysis, 34 treatment-seeking individuals with Cocaine Use Disorder received either high or low value incentives for providing a benzoylecgonine-negative urine sample or were in a control condition and received incentives for providing a urine sample regardless of the results. Participants received either escalating and resetting incentives, wherein the value of each incentive increased with consecutive negative samples and reset to the initial level upon a positive sample (Experiment 1), or fixed incentives, wherein they received the same value incentive for each negative urine sample they provided (Experiment 2). Large incentives produced more abstinence, although escalating and resetting reinforcer values did not have a differential effect. Large, fixed incentives promoted abstinence faster than other reinforcers, whereas smaller incentives resulted in poor abstinence and took many visits to achieve initial abstinence. Future research comparing different schedules on cocaine abstinence in a randomized control trial with a larger sample size is required.

Sociodemographic and clinical profile of crack cocaine treatment-seeking individuals living in "Crackland", Brazil / Perfil sociodemográfico e clínico de indivíduos em busca de tratamento para o uso de crack que vivem na "Cracolândia"

OBJECTIVE: São Paulo's Crackland is the biggest and oldest open drug use scene in Brazil, yet little is known about the profile of crack cocaine treatment-seeking individuals living in this region. The aim of this crossectional study was to describe the demographics and clinical characteristics of treatment-seeking crack users living in the Crackland region. METHODS: A sample of nighty eight individuals were screened for DSM-V substance use disorders, including substance use, impulsiveness, and psychiatric symptoms. Recent crack cocaine use was also tested using biologic specimens. RESULTS: Results indicated severe social vulnerability, as participants experienced high rates of homelessness (46.9%), unstable housing (50%), unemployment (60.4%) and early school drop-out (27.5%). The average age of crack use onset was 20 years (SD = 6.9) and the mean duration of continuous crack use was 15 years (SD = 9.7). Most participants presented with concomitant mental health disorders, particularly alcohol use disorder (87.8%), as well high rates of psychiatric symptomatology and impulsiveness. More than half of the sample reported at least one previous inpatient (73.5%) and outpatient (65.3%) addiction treatment attempt. CONCLUSION: This population profile should inform mental healthcare services, promoting the provision of tailored assistance by targeting specific demands at all levels of treatment.

OBJETIVO: Localizada em São Paulo, a Cracolândia é o maior e mais antigo cenário aberto de uso de drogas do Brasil. Ainda assim, pouco se sabe sobre o perfil dos indivíduos que vivem nessa região e buscam tratamento para crack. O objetivo deste estudo transversal foi descrever características demográficas e clínicas de usuários de crack vivendo na região da Cracolândia que estão em busca de tratamento. MÉTODOS: Noventa e oito indivíduos foram avaliados para transtornos por uso de substâncias do DSM-V, padrão de uso de substâncias, impulsividade e sintomatologia psiquiátrica. O uso recente de crack também foi determinado por meio de coleta de amostras toxicológicas. RESULTADOS: Os resultados indicaram grave vulnerabilidade social, com significativas prevalências de falta de moradia (46,9%), moradia instável (50%), desemprego (60,4%) e abandono escolar precoce (27,5%). A idade média de início do uso de crack foi de 20 anos (DP = 6,9) e a duração média do uso contínuo do crack foi de 15 anos (DP = 9,7). A maioria dos participantes apresentou alguma comorbidade psiquiátrica, particularmente transtorno por uso de álcool (87,8%), bem como altas taxas de sintomatologia psiquiátrica e impulsividade. Mais da metade da amostra relatou pelo menos uma tentativa anterior de tratamento por internação (73,5%) e ambulatorial (65,3%). CONCLUSÃO: Os achados desse estudo permitem um maior entendimento do perfil e das necessidades de usuários de crack vivendo na região da Cracolândia e podem ajudar serviços de saúde especializados em dependência química a promoverem uma assistência mais direcionada às demandas específicas dessa população.

Acceptability and feasibility of incorporating contingency management into a public treatment program for homeless crack cocaine users in Brazil: A pilot study.

Homeless substance users are particularly hard to treat. In this pilot study, we evaluated the acceptability and feasibility of incorporating Contingency Management (CM) into a public Abstinent-Contingent Housing (ACH) treatment program developed to treat currently homeless crack cocaine users. A total of 21 homeless crack cocaine users were randomized to receive 12 weeks of ACH alone (n = 9) or ACH plus CM (ACH + CM) (n = 12). Twelve treatment providers in the ACH treatment program were trained to deliver the CM intervention. CM was rated as relatively (41.7%) or very (58.3%) easy to understand and relatively (50%) or very (50%) easy to conduct by the ACH treatment providers. On a 10-point Likert scale, providers rated the importance of incorporating CM into public treatment programs for crack cocaine at M = 8.3 (SD = 2). Participants exposed to CM rated as relatively (33.3%) or very (66.7%) easy to understand. One hundred percent liked receiving the intervention "a lot," and 78.9% believed it helped them achieve and maintain crack cocaine abstinence. Finally, compared to the ACH condition, the ACH + CM condition was consistently associated with better treatment retention and cocaine use outcome measures, yelling small to large effect sizes. However, possibly due to the small sample size, most of these differences did not achieve statistical significance. CM was well integrated into the ACH treatment program and was well accepted by both the providers and participants, suggesting the feasibility of incorporating CM into a public treatment program for homeless crack cocaine users from low- and middle-income countries. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The impact of marijuana use on cocaine use outcomes among patients in methadone maintenance treatment across five trials of contingency management.

OBJECTIVE: Cocaine use is prevalent among patients in methadone maintenance and a risk factor for poor treatment outcomes. Contingency management (CM) decreases cocaine use in this population, but little is known about its efficacy when marijuana use is present prior to or during treatment. METHOD: Data from five randomized CM trials (N = 557) were used to evaluate whether: (a) marijuana frequency (none, low, or high) prior to or during treatment impacts cocaine use outcomes and (b) marijuana use differentially impacts cocaine outcomes with standard care (SC) + CM versus SC alone. RESULTS: Relative to no marijuana use, low (ß = .28, p < .01) and high marijuana use (ß = .32, p < .05) during treatment were associated with roughly 1 week shorter duration of cocaine abstinence on average. Low marijuana use (ß = .71, p < .05) during treatment was associated with a lower proportion of negative cocaine samples during treatment relative to no marijuana use. Treatment group by marijuana use (before or during treatment) interactions on duration and proportion of cocaine abstinence during treatment were not significant. For longer term outcomes, in SC + CM, marijuana use during treatment did not impact cocaine abstinence 6 months post-baseline. In SC, low (OR = .44, p < .05) and high (OR = .26, p < .001) marijuana use during treatment decreased odds of cocaine abstinence at 6 months post-baseline relative to no use. CONCLUSIONS: Findings highlight the benefits of SC + CM and abstaining from marijuana use during active treatment. At 6 months postbaseline, SC + CM evidenced similar cocaine abstinence regardless of marijuana use levels during treatment, while those with low and high marijuana use showed decreased abstinence rates in SC only. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effectiveness of incorporating contingency management into a public treatment program for people who use crack cocaine in Brazil. A single-blind randomized controlled trial.

BACKGROUND: Smoked cocaine (i.e., crack use) is a severe health problem in Brazil, with the country being reported as having the largest crack market in the world. The objective of this study was to evaluate the effectiveness of incorporating Contingency Management targeting cocaine abstinence into a public treatment program in Brazil. METHODS: Single-blind randomized controlled trial conducted at Unidade Recomeço Helvétia (URH), a public ambulatory treatment program for persons who use crack and live in the "Crackland" region in downtown São Paulo, Brazil. In total, 98 treatment-seeking individuals who use crack were randomized to one of two treatment conditions. Participants allocated to the control condition (n = 48) received 12 weeks of the standard treatment provided at URH. Participants allocated to the experimental condition (n = 50) received the same treatment in combination with Contingency Management (URH+CM). In URH+CM, participants were provided with vouchers with monetary value for submission of negative cocaine urinalysis twice weekly. RESULTS: Compared to the URH group, the URH+CM group was significantly more likely to submit a negative cocaine urinalysis during treatment, with odds ratios ranging from 4.17 to 6.78, depending on how missing data was accounted for (p<0.01). Participants receiving Contingency Management also had higher odds of achieving three or more weeks of continuous abstinence (OR= 8.07; 95% CI [2.48, 26.24]), achieved longer durations of abstinence (B = 2.14; 95% CI [0.67, 3.61]), submitted a higher percentage of negative urinalysis (B = 19.85; 95% CI [6.89, 32.82]), and were retained in treatment for a longer period (B = 3.00; 95% CI [1.04, 4.97]), compared to those receiving URH alone (p<0.01 for all). CONCLUSIONS: The incorporation of Contingency Management was effective in promoting cocaine abstinence and treatment retention. The large-scale dissemination of Contingency Management may be an effective strategy to treat Brazilians with cocaine use disorders.

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine withdrawal but increases cocaine self-administration, cocaine-induced locomotor activity, and GluR1/GluA1 in the central nucleus of the amygdala in male cocaine-dependent rats.

BACKGROUND: Cocaine addiction is a major public health problem. Despite decades of intense research, no effective treatments are available. Both preclinical and clinical studies strongly suggest that deep brain stimulation of the nucleus accumbens (NAcc) is a viable target for the treatment of cocaine use disorder (CUD). OBJECTIVE: Although previous studies have shown that DBS of the NAcc decreases cocaine seeking and reinstatement, the effects of DBS on cocaine intake in cocaine-dependent animals have not yet been investigated. METHODS: Rats were made cocaine dependent by allowing them to self-administer cocaine in extended access conditions (6 h/day, 0.5 mg/kg/infusion). The effects of monophasic bilateral high-frequency DBS (60 µs pulse width and 130 Hz frequency) stimulation with a constant current of 150 µA of the NAcc shell on cocaine intake was then evaluated. Furthermore, cocaine-induced locomotor activity, irritability-like behavior during cocaine abstinence, and the levels of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits 1 and 2 (GluR1/GluA1 and GluR2/GluA2) after DBS were investigated. RESULTS: Contrary to our expectations, DBS of the NAcc shell induced a slight increase in cocaine self-administration, and increased cocaine-induced locomotion after extended access of cocaine self-administration. In addition, DBS decreased irritability-like behavior 18 h into cocaine withdrawal. Finally, DBS increased both cytosolic and synaptosomal levels of GluR1, but not GluR2, in the central nucleus of the amygdala but not in other brain regions. CONCLUSIONS: These preclinical results with cocaine-dependent animals support the use of high-frequency DBS of the NAcc shell as a therapeutic approach for the treatment of the negative emotional state that emerges during cocaine abstinence, but also demonstrate that DBS does not decrease cocaine intake in active, long-term cocaine users. These data, together with the existing evidence that DBS of the NAcc shell reduces the reinstatement of cocaine seeking in abstinent animals, suggest that NAcc shell DBS may be beneficial for the treatment of the negative emotional states and craving during abstinence, although it may worsen cocaine use if individuals continue drug use.

Niveles plasmáticos de midkina en pacientes con trastorno por uso de cocaína en abstinencia / Plasma midkine levels in patients with cocaine use disorder during abstinence

Diversos estudios preclínicos han sugerido que la midkina endógenapodría jugar un papel modulador clave sobre los efectos neurotóxicosy adictivos de distintas drogas, incluidos los psicoestimulantes. Estahipótesis no ha sido aún explorada en humanos. Como primer pasoen esta dirección, en el presente trabajo hemos medido los nivelesplasmáticos de midkina en 75 pacientes con trastorno por uso decocaína en abstinencia y 26 controles apareados con los anteriorespor sexo, edad e índice de masa corporal. Los pacientes fueronademás divididos en un grupo de abstinencia temprana (menos deun mes, n = 30) y otro de abstinencia tardía (más de un mes, n =45). Se cuantificaron los niveles plasmáticos de midkina de todoslos participantes mediante un ensayo por inmunoabsorción ligadoa enzimas. Los pacientes en abstinencia temprana mostraron unincremento del 60% en su concentración plasmática de midkina conrespecto a los controles que tendió a desaparecer en los pacientes conperiodos de abstinencia más prolongados. Los resultados demuestranque los niveles periféricos de midkina están estrechamenterelacionados con el uso de cocaína y apoyan la idea de que dichacitoquina podría jugar un papel protector limitando la actividadbiológica de los psicoestimulantes. (AU)

Preclinical evidence suggests that endogenous midkine couldplay a key modulatory role on the neurotoxic and addictive effectsof different kinds of drugs of abuse, including psychostimulants.However, this hypothesis has not yet been explored in humans. As afirst approach to progress in this knowledge, we have comparativelystudied plasma midkine levels in 75 patients with cocaine use disorderunder abstinence and 26 control subjects matched for sex, ageand body mass index. Patients were further segmented into earlyabstinent (up to one month of abstinence, n = 30) and late-abstinent(more than one month of abstinence, n = 45). Midkine levels werequantified in plasma samples of all the participants by enzyme-linkedimmunosorbent assays. Early-abstinent patients exhibited a 60%increase of midkine plasma concentration in comparison with thecontrols. This elevation tended to normalize upon the progressionof abstinence. The results obtained demonstrate that peripheralmidkine levels are closely related to cocaine use and are consistentwith the idea that this cytokine could play a protective role by limitingthe biological activity of psychostimulants. (AU)