Agonist Medications for the Treatment of Cocaine Use Disorder

Negus, S. Stevens; Henningfield, Jack E.

doi:10.1038/npp.2014.322

Cited by 64 publications

(58 citation statements)

References 93 publications

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“…Medication Dose. Even when a drug can be studied in humans, regulatory concerns may limit how much of a drug can be given to human subjects (see Negus and Henningfield, 2015); drugs can typically be safely tested at higher doses and with more varied routes of administration in animals than in humans. One example is lisdexamfetamine, a pro-drug for D-amphetamine that showed positive results in nonhuman primates but negative results in a subsequent clinical trial .…”

Section: Variables Affecting Translationmentioning

confidence: 99%

“…To the extent that such drugs are prescribed, treatment data should be collected and used to assess and refine laboratory and clinical research. In some cases, even drugs found to be effective at all levels of analysis will face significant political and economic obstacles (regarding D-amphetamine, see Negus and Henningfield, 2015). Developing strategies to ensure that drugs that emerge from the "pipeline" can overcome such obstacles and make a meaningful impact on treatment will require the creativity and cooperation of scientists, physicians, and makers of policy.…”

Section: E Overall Conclusion and Recommendationsmentioning

confidence: 99%

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Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

2016

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Section: Variables Affecting Translationmentioning

confidence: 99%

Section: E Overall Conclusion and Recommendationsmentioning

confidence: 99%

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

2016

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“…This is why a drug that can produce addiction when smoked or injected can be used to treat addiction when given orally (methadone) or in a patch (nicotine). Similarly, amphetamine formulated to produce slowly rising and steadystate levels of drug in the brain is currently used as pharmacotherapy for cocaine addiction (Negus and Henningfield, 2015). Methadone, nicotine and amphetamine are striking examples from the clinical literature showing that manipulation of pharmacokinetic variables can fundamentally change the behavioural effects of drugs-rather than having abuse potential they might actually have therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

How fast and how often: The pharmacokinetics of drug use are decisive in addiction

Allain

Minogianis

Roberts

et al. 2015

Neuroscience & Biobehavioral Reviews

166

120

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How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, 'spiking' brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

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“…The success of methadone and nicotine replacement therapies in the treatment of opiate and nicotine addiction, respectively, has encouraged efforts to develop an indirect dopamine agonist medication to treat stimulant abuse (Grabowski et al 2004a; Rush and Stoops 2012; Negus and Henningfield 2014). Preclinical and clinical data have accumulated to suggest that drugs that release neuronal monoamines—particularly dopamine and norepinephrine—can decrease cocaine use (e.g.…”

mentioning

confidence: 99%

Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats

et al. 2015

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Rationale Like other monoamine releasers such as d-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys. Objectives The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse. Methods In Experiment 1, rats self-administered food pellets or injections of 0.19 mg/kg cocaine (i.v.) under a progressive-ratio schedule. When responding was stable, subcutaneous osmotic pumps were implanted containing saline or (+)-phenmetrazine (25 or 50 mg/kg per day). In Experiment 2, rats self-administered injections of 0.75 mg/kg cocaine under a fixed-ratio 1 schedule in daily 6-hr sessions. When responding was stable, rats were removed from the self-administration environment for 7 days and treated continuously with saline, 5 mg/kg per day d-amphetamine or phenmetrazine (25 or 50 mg/kg per day) via osmotic pumps. Rats were then returned to the self-administration context while treatment continued, and responding was extinguished by removing response-contingent stimulus changes and cocaine injections. Once responding was extinguished, reinstatement tests were conducted using cocaine injections (10 mg/kg i.p.). Results Phenmetrazine decreased self-administration of cocaine, but not food pellets, during the 14-day treatment period; effects persisted for several days after treatment was discontinued. Moreover, cocaine-induced increases in responding during the reinstatement test were attenuated by d-amphetamine and both phenmetrazine doses. Conclusions These results extend the study of the effects of phenmetrazine on cocaine self-administration to a rodent model, and provide further support for the use of monoamine releasers as agonist medications for cocaine abuse.

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Agonist Medications for the Treatment of Cocaine Use Disorder

Cited by 64 publications

References 93 publications

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

How fast and how often: The pharmacokinetics of drug use are decisive in addiction

Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats

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