A randomized placebo-controlled trial of gabapentin for cocaine dependence

Bisaga, Adam; Aharonovich, Efrat; Garawi, Fatima; Levin, Frances R.; Rubin, Eric; Raby, Wilfrid N.; Nunes, Edward V.

doi:10.1016/j.drugalcdep.2005.07.009

Cited by 76 publications

(57 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with findings from recent large-scale clinical trials demonstrating that gabapentin (1600-3200 mg/day, 6-12 weeks) had no effect on cocaine craving or urine-confirmed cocaine use (Berger et al, 2005;Bisaga et al, 2006;Hart et al, 2007;González et al, 2007). Since large-scale, double-blind clinical trials have obvious advantages over the case reports described in the Introduction, we interpret these negative findings as being more reliable and conclusive.…”

Section: Discussionsupporting

confidence: 91%

“…Early studies and small-scale (9-30 patient) open outpatient trials resulted in reports of reduced cocaine cravings and use after initiation of treatment with gabapentin (Raby, 2000;Raby and Coomaraswamy, 2004;Myrick et al, 2001;Hart et al, 2004;Haney et al, 2005). However, these findings were later challenged by other larger-scale, double-blind, placebo-controlled clinical trials demonstrating that gabapentin, at doses up to 2400-3200 mg/day for 6-12 weeks, had no effect on abstinence rates, craving or subjective effects of cocaine (Bisaga et al, 2006;Berger et al, 2005;González et al, 2007;Hart et al, 2007). However, there is no evidence demonstrating whether pretreatment with gabapentin significantly alters cocaine's direct rewarding effects or cocainetriggered reinstatement of drug-seeking behavior at preclinical levels in experimental animals.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Peng

et al. 2008

Drug and Alcohol Dependence

View full text Add to dashboard Cite

Gabapentin is a γ-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present study, we investigated the effects of gabapentin on intravenous cocaine self-administration and cocaine-triggered reinstatement of drug-seeking behavior, as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We found that gabapentin (25-200 mg/kg, i.p., 30 min or 2 h prior to cocaine) failed to inhibit intravenous cocaine (0.5 mg/kg/infusion) selfadministration under a fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine-seeking behavior. In vivo microdialysis showed that the same doses of gabapentin produced a modest increase (∼50%, p < 0.05) in extracellular NAc GABA levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no effect in the addiction-related animal behavioral models here tested. This

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Peng

et al. 2008

Drug and Alcohol Dependence

View full text Add to dashboard Cite

show abstract

“…For example, data from this laboratory demonstrated that gabapentin, a nonselective GABA agonist, significantly attenuated cocaine-induced euphoria, but did not alter cocaine self-administration (Hart et al, 2004). This finding is consistent with results from subsequent laboratory studies and an outpatient, double-blind clinical trial evaluating gabapentin for utility in treating cocaine dependence (Hart et al, 2007a, b;Bisaga et al, 2006). These observations emphasize the potential utility of assessing a measure of cocaine-taking behavior when evaluating potential pharmacotherapies for cocaine dependence.…”

Section: Introductionsupporting

confidence: 77%

“…Indeed, this is consistent with the broader literature evaluating medications for utility in treating cocaine abuse. A number of medications examined have been shown to decrease the subjective effects of cocaine when tested under controlled laboratory conditions, but the decrease in subjective effects has failed to predict clinical utility (eg gabapentin; Hart et al, 2004;Bisaga et al, 2006). In contrast, the present results argue that clinical efficacy might be best predicted by a decrease in subjective effects and cocaine selfadministration in the laboratory.…”

Section: Discussionmentioning

confidence: 36%

Smoked Cocaine Self-Administration is Decreased by Modafinil

Hart

Haney

Vosburg

et al. 2007

Neuropsychopharmacol

Self Cite

159

View full text Add to dashboard Cite

Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400 mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment-seeking cocaine-dependent individuals (n ¼ 8). Cocaine significantly increased selfadministration, subjective-effect ratings, and cardiovascular measures; modafinil at both doses (200 and 400 mg/day) markedly attenuated these effects. These findings agree with data from previous human laboratory and clinical investigations of modafinil as a potential cocaine abuse treatment medication. Thus, our data support the potential of modafinil as a pharmacotherapy for cocaine dependence.

show abstract

“…For treatment of cocaine addiction, relapse prevention presents the most promising point for intervention (O'Brien, 2005). Although initiating drug abstinence can be accomplished through in-patient treatment, maintaining out-patient cocaine abstinence has proven difficult (Gossop et al, 2003) and prolonged cocaine abstinence is achieved by only a minority of patients (Bisaga et al, 2006;Rohsenow et al, 2000;Dackis et al, 2005). This may be due to increases in cocaine craving during abstinence (Gawin and Kleber, 1986).…”

Section: Introductionmentioning

confidence: 99%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

109

126

View full text Add to dashboard Cite

Cocaine-responsive gene expression changes have been described after either no drug abstinence or short periods of abstinence. Little data exist on the persistence of these changes after long-term abstinence. Previously, we reported that after discrete-trial cocaine selfadministration and 10 days of forced abstinence, incubation of cocaine reinforcement was observable by a progressive ratio schedule. The present study used rat discrete-trial cocaine self-administration and long-term forced abstinence to examine extinction responding, mRNA abundance of known cocaine-responsive genes, and chromatin remodeling. At 30 and 100 days of abstinence, extinction responding increased compared to 3-day abstinent rats. Decreases in both medial prefrontal cortex (mPFC) and nucleus accumbens cfos, Nr4a1, Arc, and EGR1 mRNA were observed, and in most cases persisted, for 100 days of abstinence. The signaling peptides CART and neuropeptide Y (NPY) transiently increased in the mPFC, but returned to baseline levels following 10 days of abstinence. To investigate a potential regulatory mechanism for these persistent mRNA changes, levels of histone H3 acetylation at promoters for genes with altered mRNA expression were examined. In the mPFC, histone H3 acetylation decreased after 1 and 10 days of abstinence at the promoter for EGR1. H3 acetylation increased for NPY after 1 day of abstinence and returned to control levels by 10 days of abstinence.Behaviorally, these results demonstrate incubation after discrete-trial cocaine self-administration and prolonged forced abstinence. This incubation is accompanied by changes in gene expression that persist long after cessation of drug administration and may be regulated by chromatin remodeling.

show abstract

A randomized placebo-controlled trial of gabapentin for cocaine dependence

Cited by 76 publications

References 37 publications

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Smoked Cocaine Self-Administration is Decreased by Modafinil

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Contact Info

Product

Resources

About