Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with ...prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here, I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction.
Highlights • This was a double blind placebo controlled trial of modafinil for cocaine dependence. • It involved 94 subjects treated with 300 mg of modafinil or placebo daily for 8 weeks. • Modafinil ...treated subjects were more likely to achieve cocaine abstinence. • Modafinil treated subjects were more likely to report very low levels of cocaine craving. • Modafinil treated subjects were more likely to rate themselves very much improved.
Abstract Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by ...vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression.
Electroanalytical technologies as a beneficial subject of modern analytical chemistry can play an important role for abused drug analysis which is crucial for both legal and social respects. This ...article reports a novel aptamer-based biosensing procedure for cocaine analysis by combining the advantages of aptamers as selective recognition elements with the well-known advantages of biosensor systems such as the possibility of miniaturization and automation, easy fabrication and modification, low cost, and sensitivity. In order to construct the aptasensor platform, first, polythiophene bearing polyalanine homopeptide side chains (PT-Pala) was electrochemically coated onto the surface of an electrode and then cocaine aptamer was attached to the polymer via covalent conjugation chemistry. The stepwise modification of the surface was confirmed by electrochemical characterization. The designed biosensing system was applied for the detection of cocaine and its metabolite, benzoylecgonine (BE), which exhibited a linear correlation in the range from 2.5 up to 10 nM and 0.5 up to 50 μM for cocaine and BE, respectively. In order to expand its practical application, the proposed method was successfully tested for the analysis of synthetic biological fluids.
Background
Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review ...and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder.
Methods
We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacological interventions in adults with cocaine use disorder. When possible, we combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed the risk of bias of individual trials and the strength of evidence for each outcome using standardized criteria. Outcomes included continuous abstinence (3+ consecutive weeks); cocaine use; harms; and study retention. For relapse prevention studies (participants abstinent at baseline), we examined lapse (first cocaine positive or missing UDS) and relapse (two consecutive cocaine positive or missed UDS′).
Results
Sixty-six different drugs or drug combinations were studied in seven systematic reviews and 48 RCTs that met inclusion criteria. Antidepressants were the most widely studied drug class (38 RCTs) but appear to have no effect on cocaine use or treatment retention. Increased abstinence was found with bupropion (2 RCTs: RR 1.63, 95% CI 1.02 to 2.59), topiramate (2 RCTs: RR 2.56, 95% CI 1.39 to 4.73), and psychostimulants (14 RCTs: RR 1.36, 95% CI 1.05 to 1.77), though the strength of evidence for these findings was low. We found moderate strength of evidence that antipsychotics improved treatment retention (8 RCTs: RR 1.33, 95% CI 1.03 to 1.75).
Discussion
Most of the pharmacotherapies studied were not effective for treating cocaine use disorder. Bupropion, psychostimulants, and topiramate may improve abstinence, and antipsychotics may improve retention. Contingency management and behavioral interventions along with pharmacotherapy should continue to be explored.
SR Registration
Prospero CRD42018085667
•Implication of cocaine-induced neuroinflammation in the development of maladaptive cocaine-associated memories.•The role of neuroinflammation in the active process of drug-associated memory ...reconsolidation is a novel concept.•It opens new perspectives on therapies to decrease the risk of relapse to cocaine use.
Persistent and intrusive memories define a number of psychiatric disorders, including posttraumatic stress disorder and substance use disorder. In the latter, memory for drug-paired cues plays a critical role in sustaining compulsive drug use as these are potent triggers of relapse. As with many drugs, cocaine-cue associated memory is strengthened across presentations as cues become reliable predictors of drug availability. Recently, the targeting of cocaine-associated memory through disruption of the reconsolidation process has emerged as a potential therapeutic strategy; reconsolidation reflects the active process by which memory is re-stabilized after retrieval. In addition, a separate line of work reveals that neuroinflammatory markers, regulated by cocaine intake, play a role in memory processes. Our review brings these two literatures together by summarizing recent findings on cocaine-associated reconsolidation and cocaine-induced neuroinflammation. We discuss the interactions between reconsolidation processes and neuroinflammation following cocaine use, concluding with a new perspective on treatment to decrease risk of relapse to cocaine use.
Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of ...addicted individuals mainly rely on psychosocial approaches. Here we report on impairment in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.
Dopamine signaling in nucleus accumbens is essential for cocaine reward. Interestingly, imaging studies have reported blunted dopamine increases in striatum (assessed as reduced binding of ...(11)Craclopride to D2/D3 receptors) in detoxified cocaine abusers. Here, we evaluate whether the blunted dopamine response reflected the effects of detoxification and the lack of cocaine-cues during stimulant exposure. For this purpose we studied 62 participants (43 non-detoxified cocaine abusers and 19 controls) using positron emission tomography and (11)Craclopride (radioligand sensitive to endogenous dopamine) to measure dopamine increases induced by intravenous methylphenidate and in 24 of the cocaine abusers, we also compared dopamine increases when methylphenidate was administered concomitantly with a cocaine cue-video versus a neutral-video. In controls, methylphenidate increased dopamine in dorsal (effect size 1.4; P<0.001) and ventral striatum (location of accumbens) (effect size 0.89; P<0.001), but in cocaine abusers methylphenidate's effects did not differ from placebo and were similar whether cocaine-cues were present or not. In cocaine abusers despite the markedly attenuated dopaminergic effects, the methylphenidate-induced changes in ventral striatum were associated with intense drug craving. Our findings are consistent with markedly reduced signaling through D2 receptors during intoxication in active cocaine abusers regardless of cues exposure, which might contribute to compulsive drug use.
Introduccion Existe evidencia de relacion entre factores emocionales y el consumo de drogas. Sin embargo, al menos la competencia emocional y el compartimiento social de las emociones en usuarios de ...cocaina no han sido estudiados con anterioridad, en parte debido a la reciente generacion de las herramientas para su medicion. Objetivo Evaluar las caracteristicas psicometricas de la Escala de Alexitimia de Toronto (EAT), el Cuestionario de Competencias Emocionales (CEMO), y el Cuestionario de Creencias sobre los efectos de Compartimiento Social de Emociones (CCSE) en pacientes mexicanos usuarios de cocaina, asi como establecer su relacion con variables socio-demogroficas y clinicas. Metodo Los instrumentos fueron completados junto con las Escalas de Afectividad Positiva (AP) y Negativa (AN) en dos ocasiones por 158 pacientes usuarios de cocaina. Resultados Las tres escalas mostraron coeficientes alpha superiores a .70. La EAT y el CEMO presentaron alta estabilidad temporal a quince dias. La AN se asocio positivamente con la EAT y negativamente con el CEMO. La AP se correlaciono negativamente con la EAT y positivamente con el CEMO y el CCSE. El 50.9% de los pacientes presentaron una dificultad relevante en la identificacion y la expresion de sus emociones, que se relaciono de forma negativa con la escolaridad. Discusion y conclusion Se sugiere necesaria la sistematizacion de la evaluacion y el tratamiento de las dificultades en la expresion emocional de usuarios de cocaina. Las versiones en espanol de las escalas evaluadas en este estudio resultaron volidas y confiables para su uso clinico y de investigacion en pacientes mexicanos usuarios de cocaina. Palabras clave: Alexitimia, competencia emocional, cocaina, escolaridad, evaluacion. Introduction Current evidence suggests a relationship between emotional factors and drugs consumption, although at least both emotional competence and social magazine of emotions have not been studied in cocaine users, in part due to the recent generation of tools for their measure. Objective To evaluate the psychometric properties of the Toronto Alexithymia Scale (TAS), Emotional Competence Questionnaire (ECQ), and the Questionnaire about Beliefs in the effects of the Social Magazine of Emotions (QSME) in Mexican cocaine users, and to establish its relationship with socio-demographic and clinical variables. Method All instruments, as well as the Positive Affectivity (PA) and Negative Affectivity (NA) Scales, were completed twice by 158 cocaine users. Results All scales showed alpha coefficients greater than .70. The TAS and ECQ presented high temporal stability. NA was positively associated with TAS, and negatively with ESQ. PA showed a negative correlation with TAS, and a positive relation with ECQ and QSME. 50.9% of the patients had a relevant difficulty in identifying and expressing their emotions, which was negatively correlated with schooling. Discussion and conclusion A systematic evaluation and treatment of difficulties in the expression of emotions in cocaine users seems to be necessary. The Spanish versions of the scales are valid and reliable for their use with clinical and research purposes in Mexican cocaine users. Key words: Alexithymia, emotional competence, cocaine, education, assessment.
Background Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD) produces selective anticocaine ...antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving, and cardiovascular effects. Methods Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0 mg, 25 mg, 50 mg) were determined before vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 μg, n = 4; 360 μg, n = 6) were administered at weeks 1, 3, 5, and 9. Results Peak plasma antibody levels, which were highly variable, significantly predicted cocaine's effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55%–81%) reduction in ratings of good drug effect and cocaine quality, while those in the lower half showed only a nonsignificant attenuation (6%–26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer ( p < .12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. Conclusions The TA-CD vaccine substantially decreased smoked cocaine's intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence.
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