Naltrexone for the Treatment of Amphetamine Dependence: A Randomized, Placebo-Controlled Trial

Jayaram‐Lindström, Nitya; Hammarberg, Anders; Beck, Olof; Franck, Johan

doi:10.1176/appi.ajp.2008.08020304

Cited by 153 publications

(110 citation statements)

References 24 publications

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“…Taken together, this study provides support for the notion that NTX may be useful for the treatment of MA dependence, thus extending upon positive trials for stimulant dependence (Jayaram-Lindstrom et al, 2008a) and polydrug dependence (Tiihonen et al, 2012). Although no clinical trials to date have tested NTX for the treatment of MA dependence, with the exception of a small combination study (Grant et al, 2010), the present work suggests that such trials may be warranted.…”

Section: Discussionsupporting

confidence: 70%

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

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Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatmentseeking individuals meeting DSM-IV criteria for MA abuse or dependence (n = 30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

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Section: Discussionsupporting

confidence: 70%

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

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“…For example, the opioid antagonists naloxone and/or naltrexone blunted abuserelated neurochemical and behavioral effects of amphetamine in microdialysis assays of dopamine release in the striatum (Hitzemann et al, 1982;Hooks et al, 1992) and in behavioral assays of intracranial self-stimulation in rats (Esposito et al, 1980;Holtzman, 1976), place conditioning in rats (Trujillo et al, 1991), and amphetamine self-administration in rhesus monkeys (Jimenez-Gomez et al, 2011). Naltrexone also reduced amphetamine subjective effects in non-dependent and amphetamine-dependent subjects, and reduced amphetamine abuse in a placebo-controlled doubleblind clinical trial (Jayaram-Lindstrom et al, 2008a;JayaramLindstrom et al, 2008b;Jayaram-Lindstrom et al, 2004). However, opioid antagonists do not block all amphetamine effects (van Kammen and Schulz, 1985;Winslow and Miczek, 1988;Wiskerke et al, 2011;Woolfolk and Holtzman, 1997), and it is unknown whether opioid mechanisms contribute to the anti-cocaine effects of amphetamine.…”

Section: Investigate the Generality And Mechanisms Of Agonist Medicatmentioning

confidence: 99%

Agonist Medications for the Treatment of Cocaine Use Disorder

Negus

Henningfield

2014

Neuropsychopharmacol

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“…In order to provide an efficient blockade of opioid receptors, the present study used naltrexone, a clinically relevant opioid receptor antagonist with greatest affinity for the μ-and κ-opioid receptors in humans (Emmerson et al, 1994;Toll et al, 1998). The efficacy of naltrexone for substance use disorders (eg, Miranda et al, 2014;Monti et al, 1999;Ray et al, 2008;Syed and Keating, 2013), including amphetamine (Itzhak and Ali, 2002;Jayaram-Lindstrom et al, 2008) and methamphetamine (Anggadiredja et al, 2004;Ray et al, 2015a) may be subserved by its attenuation of drug craving. Naltrexone is thought to modulate reinforcementdriven behavior via blocking dopamine release in the mesolimbic dopamine system, primarily acting on the pathway from the ventral tegmental area (VTA) to the ventral striatum (ie, nucleus accumbens (NAcc)) (Benjamin et al, 1993;Lee et al, 2005); however, this theoretical pathway of naltrexone's effects on behavior has not been directly tested in human models of cue-induced craving.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

Courtney

Ghahremani

Ray

2016

Neuropsychopharmacol

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Interactions between dopaminergic and opioidergic systems have been implicated in the reinforcing properties of drugs of abuse. The present study investigated the effects of opioid blockade, via naltrexone, on functional magnetic resonance imaging (fMRI) measures during methamphetamine cue-reactivity to elucidate the role of endogenous opioids in the neural systems underlying drug craving. To investigate this question, non-treatment seeking individuals with methamphetamine use disorder (N = 23; 74% male, mean age = 34.70 (SD = 8.95)) were recruited for a randomized, placebo controlled, within-subject design and underwent a visual methamphetamine cue-reactivity task during two blood-oxygen-level dependent (BOLD) fMRI sessions following 3 days of naltrexone (50 mg) and matched time for placebo. fMRI analyses tested naltrexone-induced differences in BOLD activation and functional connectivity during cue processing. The results showed that naltrexone administration reduced cue-reactivity in sensorimotor regions and related to altered functional connectivity of dorsal striatum, ventral tegmental area, and precuneus with frontal, visual, sensory, and motor-related regions. Naltrexone also weakened the associations between subjective craving and precuneus functional connectivity with sensorimotor regions and strengthened the associations between subjective craving and dorsal striatum and precuneus connectivity with frontal regions. In conclusion, this study provides the first evidence that opioidergic blockade alters neural responses to drug cues in humans with methamphetamine addiction and suggests that naltrexone may be reducing drug cue salience by decreasing the involvement of sensorimotor regions and by engaging greater frontal regulation over salience attribution.

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Naltrexone for the Treatment of Amphetamine Dependence: A Randomized, Placebo-Controlled Trial

Abstract: This trial demonstrated the efficacy of naltrexone in reducing amphetamine use in amphetamine-dependent individuals.

Cited by 153 publications

References 24 publications

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Agonist Medications for the Treatment of Cocaine Use Disorder

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

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