Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: A pilot study

Grassi, Maria Caterina; Cioce, Anna Maria; Giudici, Franco Dei; Antonilli, Letizia; Nencini, Paolo

doi:10.1016/j.phrs.2006.11.005

Cited by 39 publications

(28 citation statements)

References 33 publications

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“…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 cocaineelicited craving in the laboratory (Hart et al 2004(Hart et al , 2007aFischman 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). …”

Section: Self-administration Versus Other Modelsmentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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Rationale 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. Objective 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. Results 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. Conclusions 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.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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Section: Self-administration Versus Other Modelsmentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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“…However, recent controlled trials of several medications, namely, disulfiram, topiramate, modafinil, and others, suggested that some medications added to counseling may provide an advantage over placebo treatment for cocaine dependence (See respectively : Carroll, Fenton, Ball, Nich et al, 2004;Dackis, Kampman, Lynch, Pettinati et al, 2005;Kampman, Pettinati, Lynch, Dackis et al, 2004). To date, however, disulfiram has had more published articles than any other medication in support for its use in the treatment of cocaine dependence (see Carroll et al, 2004;Carroll, Nich, Ball, McCance et al, 2000;Carroll, Nich, Ball, Mccance et al, 1998;Gossop & Carroll, 2006;Grassi, Cioceb, Dei Giudicib, Antonillia et al, 2007), particularly in men (Nich, McCance-Katzb, Petrakis, Cubellsa et al, 2004;Petrakis, Carroll, Nich, Gordon et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence

Pettinati

Kampman

Lynch

et al. 2008

Addictive Behaviors

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BACKGROUND-This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence.METHODS-208 patients were randomized to disulfiram (250mg/day), naltrexone (100mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.RESULTS-Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiramnaltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol.CONCLUSION-There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.

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“…The relevance of these findings to DBH inhibition as a potential pharmacotherapy for cocaine relapse prevention remains to be determined. Although several clinical trials with disulfiram showed a positive result for treatment of cocaine use (Carroll et al, 1998(Carroll et al, , 2004George et al, 2000;Petrakis et al, 2000;Grassi et al, 2007), some subsequent studies have been less encouraging. For example, in one clinical trial, low doses of disulfiram treatment resulted in worse retention and increased cocaine-positive urine samples (Oliveto et al, 2011).…”

Section: Effects Of Dopamine B-hydroxylase Inhibition In Monkeysmentioning

confidence: 99%

Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys

Cooper¹,

Kimmel²,

Manvich³

et al. 2014

J Pharmacol Exp Ther

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Disulfiram has shown promise as a pharmacotherapy for cocaine dependence in clinical settings, although it has many targets, and the behavioral and molecular mechanisms underlying its efficacy are unclear. One of many biochemical actions of disulfiram is inhibition of dopamine b-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. Thus, disulfiram simultaneously reduces NE and elevates DA tissue levels in the brain. In rats, both disulfiram and the selective DBH inhibitor nepicastat block cocaine-primed reinstatement, a paradigm which is thought to model some aspects of drug relapse. This is consistent with some clinical results and supports the use of DBH inhibitors for the treatment of cocaine dependence. The present study was conducted to confirm and extend these results in nonhuman primates. Squirrel monkeys trained to self-administer cocaine were pretreated with disulfiram or nepicastat prior to cocaineinduced reinstatement sessions. Neither DBH inhibitor altered cocaine-induced reinstatement. Unexpectedly, nepicastat administered alone induced a modest reinstatement effect in squirrel monkeys, but not in rats. To investigate the neurochemical mechanisms underlying the behavioral results, the effects of DBH inhibition on extracellular DA were analyzed in the nucleus accumbens (NAc) using in vivo microdialysis in squirrel monkeys. Both DBH inhibitors attenuated cocaine-induced DA overflow in the NAc. Hence, the attenuation of cocaine-induced changes in accumbal DA neurochemistry was not associated with altered cocaine-seeking behavior. Overall, the reported behavioral effects of DBH inhibition in rodent models of relapse did not extend to nonhuman primates under the conditions used in the current studies.

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Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: A pilot study

Cited by 39 publications

References 33 publications

Controversies in translational research: drug self-administration

Controversies in translational research: drug self-administration

A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence

Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys

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