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disulfiram cocaine

R David Heekin, Daryl Shorter, Thomas R Kosten
Substance use disorders (SUD) are a significant threat to both individual and public health. To date, SUD pharmacotherapy has focused primarily on agonist medications (i.e. nicotine replacement therapy for tobacco use disorder; methadone and buprenorphine for opioid use disorder), antagonist medications (i.e. naltrexone for opioid use disorder), and aversive therapy (i.e. disulfiram for alcohol use disorder). Pharmacotherapeutic approaches utilizing an immunological framework for medication development represent an important focus of study for treatment of these illnesses...
November 2017: Expert Review of Vaccines
Elise E DeVito, Guangheng Dong, Hedy Kober, Jiansong Xu, Kathleen M Carroll, Marc N Potenza
A growing literature exists on neural correlates of treatment outcome. However, different types-or components of-treatment have distinct theorized mechanisms of action. And it is not yet known how changes in neural activity across treatment relate to engagement in different treatment components. Participants with cocaine use disorders in a randomized clinical trial received cognitive-behavioral therapy (CBT) plus, in a 2 × 2 design, contingency management (CM) or no CM, and disulfiram or placebo. Participants performed a functional MRI Stroop task, a measure of cognitive control, at the beginning of and after the 12-week treatment...
August 2017: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
Ihsan M Salloum, Edson Sherwood Brown
BACKGROUND: The comorbidity of substance use disorders (SUDs) in bipolar disorder is among the highest in psychiatric disorders. Evidence-based controlled psychosocial or pharmacological interventions trials, which may guide treatment decisions, have not been systematically reviewed. OBJECTIVE: To present a narrative review of the public health and clinical significance of this condition, including diagnostic and treatment implications, and to evaluate controlled trials conducted to date...
July 2017: American Journal of Drug and Alcohol Abuse
Felipe Gil, Arthur Guerra de Andrade, João Maurício Castaldelli-Maia
The consumption of alcohol, tobacco, and other drugs has become a concern in high-performance athletes. Professional athletes are more exposed to drugs than the general population. Although some drugs are unquestionably detrimental to performance, several studies have nevertheless shown evidence of increased consumption of these substances within this sub-population. This review aimed to elucidate alcohol, tobacco, cocaine, cannabis, and opioid use among high-performance athletes, discussing the prevalence of substance use, its impacts, and alternatives to treatment in this special population...
December 2016: International Review of Psychiatry
Carlos Roncero, Alfonso C Abad, Antonio Padilla-Mata, Elena Ros-Cucurull, Carmen Barral, Miquel Casas, Lara Grau-López
BACKGROUND: In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. OBJECTIVE: Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. METHODS: Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia")...
2017: Current Neuropharmacology
Kathleen M Carroll, Charla Nich, Nancy M Petry, Dorothy A Eagan, Julia M Shi, Samuel A Ball
BACKGROUND: This study evaluated the extent to which the addition of disulfiram and contingency management for adherence and abstinence (CM), alone and in combination, might enhance the effects of cognitive behavioral therapy (CBT) for cocaine use disorders. METHODS: Factorial randomized double blind (for medication condition) clinical trial where CBT served as the platform and was delivered in weekly individual sessions in a community-based outpatient clinic. 99 outpatients who met DSM-IV criteria for current cocaine dependence were assigned to receive either disulfiram or placebo, and either CM or no CM...
March 1, 2016: Drug and Alcohol Dependence
Michael Soyka, Jochen Mutschler
Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption...
October 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Paola Devoto, Giovanna Flore, Pierluigi Saba, Roberto Frau, Gian L Gessa
INTRODUCTION: Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase...
October 2015: Brain and Behavior
Isabelle E Bauer, David P Graham, Jair C Soares, David A Nielsen
Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders...
2015: Pharmacogenomics
Robert D Winefield, Anthonius A M Heemskerk, Swetha Kaul, Todd D Williams, Michael J Caspers, Thomas E Prisinzano, Elinore F McCance-Katz, Craig E Lunte, Morris D Faiman
Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain...
March 25, 2015: Journal of Pharmaceutical and Biomedical Analysis
Martin Grosshans, Jochen Mutschler, Falk Kiefer
The treatment of cocaine dependence is difficult as no approved pharmacotherapy is available as yet. However, in preclinical and clinical trials, a variety of compounds were tested for suitability as inhibitors of craving for and relapse into the use of cocaine, among these antidepressants, antiepileptics, dopamine agonists, disulfiram, and naltrexone. Nalmefene, a structural derivative of naltrexone, shares with its parent compound approval (granted by the European Medical Agency in 2013) as a medication for the treatment of alcohol addiction in the European Union...
July 2015: International Clinical Psychopharmacology
Elise E DeVito, Theresa A Babuscio, Charla Nich, Samuel A Ball, Kathleen M Carroll
BACKGROUND: Despite extensive research on gender differences in addiction, there are relatively few published reports comparing treatment outcomes for women versus men based on evidence-based treatments evaluated in randomized clinical trials. METHODS: An aggregate sample comprised of data from five randomized clinical trials of treatment for cocaine dependence (N = 434) was evaluated for gender differences in clinical outcomes. Secondary analyses compared gender differences in outcome by medication condition (disulfiram versus no medication) and across multiple behavioral treatment conditions...
December 1, 2014: Drug and Alcohol Dependence
Paola Devoto, Liana Fattore, Silvia Antinori, Pierluigi Saba, Roberto Frau, Walter Fratta, Gian Luigi Gessa
Previous investigations indicate that the dopamine-β-hydroxylase (DBH) inhibitors disulfiram and nepicastat suppress cocaine-primed reinstatement of cocaine self-administration behaviour. Moreover, both inhibitors increase dopamine release in the rat medial prefrontal cortex (mPFC) and markedly potentiate cocaine-induced dopamine release in this region. This study was aimed to clarify if the suppressant effect of DBH inhibitors on cocaine reinstatement was mediated by the high extracellular dopamine in the rat mPFC leading to a supra-maximal stimulation of D1 receptors in the dorsal division of mPFC, an area critical for reinstatement of cocaine-seeking behaviour...
January 2016: Addiction Biology
Debra A Cooper, Heather L Kimmel, Daniel F Manvich, Karl T Schmidt, David Weinshenker, Leonard L Howell
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 β-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...
July 2014: Journal of Pharmacology and Experimental Therapeutics
Piotr Dzien, Mikko I Kettunen, Irene Marco-Rius, Eva M Serrao, Tiago B Rodrigues, Timothy J Larkin, Kerstin N Timm, Kevin M Brindle
PURPOSE: Aldehyde dehydrogenase (ALDH2) is an emerging drug target for the treatment of heart disease, cocaine and alcohol dependence, and conditions caused by genetic polymorphisms in ALDH2. Noninvasive measurement of ALDH2 activity in vivo could inform the development of these drugs and accelerate their translation to the clinic. METHODS: [1-(13) C, U-(2) H5 ] ethanol was hyperpolarized using dynamic nuclear polarization, injected into mice and its oxidation in the liver monitored using (13) C MR spectroscopy and spectroscopic imaging...
May 2015: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Marilyn D Skinner, Pierre Lahmek, Héloïse Pham, Henri-Jean Aubin
BACKGROUND: Despite its success with compliant or supervised patients, disulfiram has been a controversial medication in the treatment of alcoholism. Often, study designs did not recognize a pivotal factor in disulfiram research, the importance of an open-label design. Our objectives are: (1) to analyze the efficacy and safety of disulfiram in RCTs in supporting abstinence and (2) to compare blind versus open-label studies, hypothesizing that blinded studies would show no difference between disulfiram and control groups because the threat would be evenly spread across all groups...
2014: PloS One
Richard S Schottenfeld, Marek C Chawarski, Joseph F Cubells, Tony P George, Jaakko Lappalainen, Thomas R Kosten
BACKGROUND: Disulfiram may be efficacious for treating cocaine dependence or abuse, possibly through inhibiting dopamine β-hydroxylase (DβH). Consequently, this randomized, placebo-controlled clinical trial of disulfiram during buprenorphine maintenance treatment evaluated the study hypothesis that disulfiram is superior to placebo and explored whether disulfiram response is greatest for participants with a single nucleotide polymorphism coding for genetically low DβH (T-allele carriers)...
March 1, 2014: Drug and Alcohol Dependence
Brian D Kiluk, Theresa A Babuscio, Charla Nich, Kathleen M Carroll
Smoking cocaine achieves maximal concentration and effect far more rapidly than through the intranasal ("snorting") route, and it is associated with greater propensity for dependence and more severe consequences. However, very little is known about differences in treatment outcome according to route of administration. This study compared treatment outcomes, such as frequency of cocaine use and Addiction Severity Index (ASI) composite scores, by primary route of cocaine administration (smoking vs. intranasal) among a pooled sample of 412 cocaine-dependent individuals participating in 1 of 5 randomized clinical trials...
December 2013: Experimental and Clinical Psychopharmacology
Gillian M Keating
A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients...
January 2014: Clinical Drug Investigation
Elinore F McCance-Katz, Valerie A Gruber, George Beatty, Paula Lum, Qing Ma, Robin DiFrancesco, Jill Hochreiter, Paul K Wallace, Morris D Faiman, Gene D Morse
BACKGROUND AND OBJECTIVES: Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS. METHOD: This pharmacokinetics study (n=40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction...
March 2014: American Journal on Addictions
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