Behavioral, physiological, and pharmacological interaction of cocaine and disulfiram in humans

Hameedi, Faiq; Rosen, Marc I.; McCance‐Katz, Elinore F.; McMahon, Thomas J.; Price, Lawrence H.; Jatlow, Peter; Woods, Scott W.; Kosten, Thomas R.

doi:10.1016/0006-3223(94)00361-6

Cited by 72 publications

(59 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

Disulfiram enhances subjective effects of dextroamphetamine in humans

Sofuoglu

Poling

Waters

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 93%

Disulfiram enhances subjective effects of dextroamphetamine in humans

Sofuoglu

Poling

Waters

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

show abstract

“…Disulfiram treatment increased cocaine plasma levels and decreased cocaine clearance in humans following intranasal cocaine administration (McCance-Katz et al, 1998a,b;Hameedi et al, 1995;Baker et al, 2007). Thus, it is possible that the disulfiram-induced increase in CIS was a direct result of decreased cocaine metabolism.…”

Section: Discussionmentioning

confidence: 99%

Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures

Gaval-Cruz

Schroeder

Liles

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

The antialcoholism drug disulfiram has shown recent promise as a pharmacotherapy for treating cocaine dependence, probably via inhibition of dopamine β-hydroxylase (DBH), the enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE). We previously showed that DBH knockout (Dbh -/-) mice, which lack NE, are susceptible to seizures and are hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, suggesting that disulfiram might exacerbate cocaine-induced seizures (CIS) by inhibiting DBH. To test this, we examined CIS in wild-type and Dbh -/-mice following administration of disulfiram or the selective DBH inhibitor nepicastat. We found that Dbh genotype had no effect on CIS probability or frequency, whereas disulfiram, but not nepicastat, increased the probability of having CIS in both wild-type and Dbh -/-mice. Both disulfiram and nepicastat increased CIS frequency in wild-type but not Dbh -/-mice. There were no genotype or treatment effects on serum cocaine levels, except for an increase in disulfiram-treated Dbh -/-mice at the highest dose of cocaine. These results suggest that disulfiram enhances CIS via two distinct mechanisms: it both increases CIS frequency by inhibiting DBH and increases CIS frequency in a DBH-independent manner.

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

Behavioral, physiological, and pharmacological interaction of cocaine and disulfiram in humans

Cited by 72 publications

References 4 publications

Disulfiram enhances subjective effects of dextroamphetamine in humans

Disulfiram enhances subjective effects of dextroamphetamine in humans

Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures

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

Contact Info

Product

Resources

About