Amphetamine induced endogenous opioid release in the human brain detected with [11C]carfentanil PET: replication in an independent cohort

Mick, Inge; Myers, Jim; Stokes, Paul; Erritzoe, David; Colasanti, Alessandro; Bowden‐Jones, Henrietta; Clark, Luke; Gunn, Roger N.; Rabiner, Eugenii A.; Searle, Graham; Waldman, Adam D.; Parkin, Mark C.; Brailsford, Alan D.; Nutt, David; Lingford‐Hughes, Anne

doi:10.1017/s1461145714000704

Cited by 94 publications

(58 citation statements)

References 18 publications

(20 reference statements)

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“…Acute oral amphetamine administration has been shown to induce endogenous opioid release in many brain regions frequently implicated in addiction, including the basal ganglia, frontal cortex areas, thalamus, and striatum (Colasanti et al, 2012;Mick et al, 2014). Further, elevated frontal/temporal cortical μ-opioid receptor binding has been observed in cocaine dependence, the degree of which was shown to positively correlate with self-reported cocaine craving (Gorelick et al, 2005), and relate to relapse following treatment (Ghitza et al, 2010;Gorelick et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Although the primary targets of amphetamine are the dopamine and norepinephrine transporters (Rothman et al, 2001), amphetamine also promotes the release of endogenous opioids (Mick et al, 2014). Furthermore, opioid antagonist doses that do not alter abuse-related cocaine effects have been shown to reduce amphetamine effects.…”

Section: Introductionmentioning

confidence: 99%

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Moerke

Banks

Cheng

et al. 2017

Drug and Alcohol Dependence

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Background Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Methods Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0–0.1 mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. Results During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032–0.32 mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032 mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032 mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. Conclusions These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption.

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“…Identifying the substrates of addiction in an attempt to elucidate potential neural targets for future treatment development in substance dependence remains a major challenge in neuroscience. One such neural target is the brain's opioid system, given its interactions with the dopamine (DA) system of the brain (Solinas et al, 2004), and its role in the reinforcing effects of alcohol and other substances of abuse (Colasanti et al, 2012;Mick et al, 2014;Spreckelmeyer et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Acute naltrexone does not remediate fronto‐striatal disturbances in alcoholic and alcoholic polysubstance‐dependent populations during a monetary incentive delay task

et al. 2016

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There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, due to its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled fMRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and "missed" rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.

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Amphetamine induced endogenous opioid release in the human brain detected with [11C]carfentanil PET: replication in an independent cohort

Cited by 94 publications

References 18 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

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Acute naltrexone does not remediate fronto‐striatal disturbances in alcoholic and alcoholic polysubstance‐dependent populations during a monetary incentive delay task

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