Disulfiram effects on acute cocaine administration

McCance‐Katz, Elinore F.; Kosten, Thomas R.; Jatlow, Peter

doi:10.1016/s0376-8716(98)00050-7

Cited by 101 publications

(79 citation statements)

References 42 publications

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“…Although a previous study combining disulfiram with intranasal cocaine reported modest enhancement of cocaine-induced heart rate and blood pressure increases (McCance-Katz et al, 1998), intravenous cocaine, which is closer to the potency of amphetamine by any route of administration, did not enhance the cocaine-induced blood pressure and heart rate increases (Baker et al, 2007). Thus, the combination of disulfiram and amphetamine appears medically safe.…”

Section: Discussionmentioning

confidence: 76%

“…Previous research involving disulfiram and cocaine found that disulfiram increased the rating of "nervousness" and "paranoia" from intranasal cocaine, without affecting the rating of "high" (Hameedi et al, 1995;McCance-Katz et al, 1998). In a more recent study, Baker et al (2007) reported that disulfiram treatment attenuated the "high" from intravenous cocaine but enhanced the rating of "anxious", suggesting that disulfiram's efficacy in reducing cocaine use may be due its attenuation of the cocaine-induced euphoria and/or enhancement of cocaine-induced aversive subjective effects.…”

Section: Discussionmentioning

confidence: 93%

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Disulfiram enhances subjective effects of dextroamphetamine in humans

Sofuoglu

Poling

Waters

et al. 2008

Pharmacology Biochemistry and Behavior

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Disulfiram has shown promise in several clinical trials for cocaine addiction, but its potential utility in the treatment of amphetamine addiction has not been examined. The goal of this study was to determine the effects of disulfiram on acute physiological and subjective responses to dextroamphetamine in healthy volunteers. Five male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects were randomly assigned to a sequence of disulfiram (250 mg/day) or placebo treatments each lasting for 4 days. Day four of each treatment period was the experimental session, in which subjects orally ingested a single dose of dextroamphetamine (20 mg/70 kg). Outcome measures included heart rate, blood pressure, plasma cortisol and prolactin, subjective and performance on the Sustained Attention to Response Test (SART). Disulfiram did not affect dextroamphetamine-induced increases in heart rate, blood pressure, cortisol, or prolactin. Disulfiram did enhance some of the subjective effects of dextroamphetamine including ratings of "high," "anxious," "bad drug effects," "want more drug" and "drug liking" and was also associated with decreased performance in the SART test. How these enhanced subjective amphetamine responses affect cocaine use behavior remains to be determined in future clinical trials.Disulfiram enhances subjective effects of dextroamphetamine in humans. Amphetamine abuse, especially methamphetamine, is an important public health problem in the US, with an estimated 1.4 million have reported methamphetamine use during the past year (SAMHSA, 2004). There are no approved pharmacotherapies for the treatment of amphetamine (Hill and Sofuoglu, 2007) or cocaine addiction, the other commonly used stimulant (Sofuoglu and Kosten, 2006). Given the similarities between the pharmacological effects of cocaine and amphetamines (Fischman et al., 1976), it is plausible that potential pharmacotherapies may be effective for both cocaine and amphetamine addiction. One of the promising medications for cocaine addiction is disulfiram (Antabuse), which has been shown to reduce cocaine abuse and relapse in outpatient clinical trials (Carroll et al., 1993;Carroll et al., 2004;Carroll et al., 1998;George et al., 2000;Petrakis et al., 2000). Disulfiram is approved by the Food and Drug Mehmet Sofuoglu, Yale University, Department of Psychiatry, VA Connecticut Healthcare System, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT 06516, Phone: (203) Fax: (203) 937-3478, e-mail: Mehmet.Sofuoglu@yale.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the j...

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 93%

Disulfiram enhances subjective effects of dextroamphetamine in humans

Sofuoglu

Poling

Waters

et al. 2008

Pharmacology Biochemistry and Behavior

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“…42,43 In addition, some cocainedependent subjects experience intense dysphoria during nasal cocaine self-administration after pretreatment with disulfiram. [44][45][46] CSF levels of D␤H predict disulfiram-induced paranoia and dysphoria in alcoholic subjects. 47 Paranoid reactions to cocaine are consistently described by cocaine users as highly unpleasant, and often motivate users to seek treatment for cocaine dependence.…”

Section: Discussionmentioning

confidence: 99%

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

et al. 2000

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Low levels of dopamine ␤-hydroxylase (D␤H) protein in the plasma or cerebrospinal fluid (CSF) are associated with greater vulnerability to positive psychotic symptoms in several psychiatric disorders. D␤H level is a stable, genetically controlled trait. DBH, the locus encoding D␤H protein, is the major quantitative trait locus controlling plasma and CSF D␤H levels. We therefore hypothesized that DBH variants or haplotypes, associated with low levels of D␤H in the plasma, would also associate with greater vulnerability to cocaine-induced paranoia. To test this hypothesis, we first showed that a di-allelic variant, DBH*5Ј-ins/del, located approximately 3 kb 5Ј to the DBH transcriptional start site, significantly associates with plasma D␤H activity in European-Americans (n = 66). Linkage disequilibrium analysis of that polymorphism and DBH*444g/a, another di-allelic variant associated with D␤H levels, demonstrated that alleles of similar association to D␤H levels are in positive disequilibrium. We then estimated DBH haplotype frequencies in cocaine-dependent European Americans rated for cocaine-induced paranoia (n = 45). As predicted, the low-D␤H-associated haplotype, Del-a, was significantly more frequent (P = 0.0003) in subjects endorsing cocaine-induced paranoia (n = 29) than in those denying it (n = 16). Comparison to control haplotype frequencies (n = 145 healthy European-Americans) showed that the association predominantly reflected under-representation of Del-a haplotypes in those denying cocaine-induced paranoia. We conclude that: (a) the two DBH polymorphisms we studied are associated with plasma DBH levels; (b) those two polymorphisms are in significant linkage disequilibrium in European Americans, with alleles of similar association to D␤H levels in positive disequilibrium; and (c) the haplotype associated with low DBH activity is also associated with cocaine-induced paranoia. Molecular Psychiatry (2000) 5, 56-63.Keywords: psychotic disorders; substance-related disorders; central nervous system stimulants; norepinephrine; catecholamines; schizophrenia; alleles; genes More than 60% of experienced cocaine users report paranoia during cocaine intoxication, while the remainder deny even mild cocaine-induced paranoia (CIP), despite reporting similar routes of administration, duration of cocaine dependence, and lifetime and per-binge quantities of cocaine ingested. 1-3 Satel and Edell 4 reported elevated scores on a measure of psychosis proneness in cocaine-dependent subjects who endorsed CIP compared to those who did not. These data suggest the presence of substantial interindividual variation in vulnerability to CIP. Evidence for genetic influences on vulnerability to drug-induced paranoiaSeveral lines of evidence support genetic factors as modulators of individual vulnerability to CIP. Numerous animal studies support the importance of genetic factors in behavioral responses to cocaine. 5 Abstinent human cocaine users who endorse CIP exhibit deficits in P50 sensory gating of auditory stimuli, 6 a heritable p...

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“…Potentially, disulfiram's mechanism of action for reducing cocaine use is that it inhibits dopamine beta-hydroxylase, an enzyme that normally converts dopamine to noradrenaline (Kosten, George, & Kosten, 2002;McCance-Katz, Kosten, & Jatlow, 1998a), and hence, increases the concentration of dopamine more than what is observed when cocaine is taken alone. Furthermore, disulfiram, when coupled with cocaine use, impedes cocaine metabolism by inhibiting plasma and microsomal carboxylesterases and plasma cholinesterase (McCanceKatz, Kosten, & Jatlow, 1998b). In some studies, the combination of disulfiram and cocaine have resulted in a higher than expected plasma-cocaine concentration, and a longer than expected cocaine-elimination half-life (Hameedi, Rosen, McCance-Katz, McMahon et al, 1995;McCance-Katz, Kosten, & Jatlow, 1998a).…”

Section: Introductionmentioning

confidence: 99%

“…In some studies, the combination of disulfiram and cocaine have resulted in a higher than expected plasma-cocaine concentration, and a longer than expected cocaine-elimination half-life (Hameedi, Rosen, McCance-Katz, McMahon et al, 1995;McCance-Katz, Kosten, & Jatlow, 1998a). These effects of the disulfiram-cocaine interaction might result in an exacerbation of negative effects of cocaine, such as anxiety, paranoia, and cardiovascular response (McCance-Katz, Kosten, & Jatlow, 1998a, 1998b.…”

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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Disulfiram effects on acute cocaine administration

Cited by 101 publications

References 42 publications

Disulfiram enhances subjective effects of dextroamphetamine in humans

Disulfiram enhances subjective effects of dextroamphetamine in humans

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

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

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