Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: A pilot study
ABSTRACT Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.
- SourceAvailable from: Colin N Haile
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- "Results from randomized clinical trials assessing therapeutic efficacy of disulfiram for cocaine dependence also appear complex. For instance, studies have found that disulfiram treatment decreases (Carroll et al., 1993; Higgins et al., 1993; Carroll et al., 2000; George et al., 2000; Grassi et al., 2007) or produces no change (Pettinati et al., 2008) in cocaine use. Patients in the study by Pettinati et al. were also dependent on alcohol, and only 1/3 took >80% of their disulfiram doses, which likely contributed to the lack of efficacy for disulfiram in this study. "
ABSTRACT: Much effort has been devoted to research focused on pharmacotherapies for cocaine dependence yet there are no FDA-approved medications for this brain disease. Preclinical models have been essential to defining the central and peripheral effects produced by cocaine. Recent evidence suggests that cocaine exerts its reinforcing effects by acting on multiple neurotransmitter systems within mesocorticolimibic circuitry. Imaging studies in cocaine-dependent individuals have identified deficiencies in dopaminergic signaling primarily localized to corticolimbic areas. In addition to dysregulated striatal dopamine, norepinephrine and glutamate are also altered in cocaine dependence. In this review, we present these brain abnormalities as therapeutic targets for the treatment of cocaine dependence. We then survey promising medications that exert their therapeutic effects by presumably ameliorating these brain deficiencies. Correcting neurochemical deficits in cocaine-dependent individuals improves memory and impulse control, and reduces drug craving that may decrease cocaine use. We hypothesize that using medications aimed at reversing known neurochemical imbalances is likely to be more productive than current approaches. This view is also consistent with treatment paradigms used in neuropsychiatry and general medicine.Pharmacology [?] Therapeutics 01/2012; 134(2):260-77. DOI:10.1016/j.pharmthera.2012.01.010 · 7.75 Impact Factor
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- "Several other randomized controlled trials showed the efficacy of DSF in treating cocaine dependence   with significantly better outcomes in men than those found in women . A recent meta-analysis  included seven studies of those reported in the literature, selected according to pre-established criteria. "
ABSTRACT: Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.05/2011; 6(2):146-60. DOI:10.2174/157488911795933893
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- "Although there are examples in which medications, such as amantadine, bromocriptine, and phenytoin, failed to decrease cocaine intoxication in the laboratory (Collins et al. 2003; Preston et al. 1992; Sofuoglu et al. 1999) and also failed to decrease cocaine use in clinical trials (Kampman et al. 2006; de Lima et al. 2002; Gorelick and Wilkins 2006), overall, cocaine's subjective effects appear to be more sensitive to modulation by medications, resulting in a high rate of false positives when this is the primary outcome measured (see also Comer et al. 2008a). A vast array of compounds including gabapentin, desipramine, pergolide, risperidone, ecopipam, selegeline, venlafaxine, and naltrexone, for example, have been shown to decrease ratings of a cocaine intoxication or cocaine-elicited craving in the laboratory (Hart et al. 2004, 2007a, b; Fischman et al. 1990; Haney et al. 1998; Romach et al. 1999; Newton et al. 1999; Foltin et al. 2003; Sofuoglu et al. 2003), yet none of these compounds decreased cocaine use in controlled clinical trials (Bisaga et al. 2006; Campbell et al. 2003; Malcolm et al. 2000; Grabowski et al. 2000; Elkashef et al. 2006; Ciraulo et al. 2005; Grassi et al. 2007). "
ABSTRACT: Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Psychopharmacology 09/2008; 199(3):403-19. DOI:10.1007/s00213-008-1079-x · 3.99 Impact Factor