Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine

Stoops, William W.; Pike, Erika; Hays, Lon R.; Glaser, Paul E.A.; Rush, Craig R.

doi:10.1016/j.pbb.2014.11.018

Cited by 27 publications

(25 citation statements)

References 33 publications

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“…Naltrexone did not significantly decrease methamphetamine self-administration in a previous human laboratory study that used similar methods. 33 However, the present results are in agreement with larger clinical trials that demonstrated a reduction in amphetamine-positive urine samples during naltrexone treatment relative to placebo. 64,65 Naltrexone did not alter self-administration of 30 mg methamphetamine, however, indicating that the ability of naltrexone to attenuate the reinforcing effects of methamphetamine is surmountable by higher doses.…”

Section: Discussionsupporting

confidence: 91%

“…27 In human laboratory experiments, acute pretreatment with naltrexone 11,28,29 and alprazolam 11,30 reduced the subject-rated effects of d -amphetamine in separate studies. Maintenance on 1 mg/day alprazolam XR also produced a small, but orderly attenuation of some subject-rated effects of methamphetamine 31 , and likewise, maintenance on 50 mg/day naltrexone modestly decreased a subset of “positive” subject-rated drug effects of intravenous methamphetamine 32 , in individuals who met criteria for stimulant-use disorders (but see 33 ).…”

Section: Introductionmentioning

confidence: 97%

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Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Marks

Lile

Stoops

et al. 2016

Journal of Clinical Psychopharmacology

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Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric acid type A (GABAA) receptors (e.g., alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of d-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and “positive” subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone. Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6–7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected. Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like “positive” subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10 mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 97%

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Marks

Lile

Stoops

et al. 2016

Journal of Clinical Psychopharmacology

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“…The present results were consistent with previous clinical trials demonstrating weak or no bupropion treatment efficacy for methamphetamine addiction (Elkashef et al, 2008;Heinzerling et al, 2014;Shoptaw et al, 2008) and a recent human laboratory study demonstrating no bupropion treatment efficacy on methamphetamine choice (Stoops et al, 2015). The present results were also somewhat consistent with previous findings examining acute bupropion pretreatments on methamphetamine self-administration in rhesus monkeys (Schindler et al, 2011).…”

Section: Effects Of Bupropion and Risperidone On Methamphetamine Choicesupporting

confidence: 92%

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys

Banks

Blough

2015

Neuropsychopharmacol

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Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food choice model.

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“…Methamphetamine also produced a constellation of prototypical stimulant-like subjective effects indicative of abuse potential (e.g., Good Effects and Like Drug) and elevated systolic and diastolic blood pressure. These effects are consistent with the type and magnitude of effects typically observed following methamphetamine administration by various routes (e.g., Hart et al, 2001; Kirkpatrick et al, 2012; Marks et al, 2016; Pike et al, 2016; Stoops et al, 2015), but was not impacted by buspirone maintenance.…”

Section: Discussionsupporting

confidence: 85%

Buspirone maintenance does not alter the reinforcing, subjective, and cardiovascular effects of intranasal methamphetamine

Reynolds

Strickland

Stoops

et al. 2017

Drug and Alcohol Dependence

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Background Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. Methods Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30 mg) were assessed after at least 6 days of buspirone (0 and 45 mg/day) maintenance. Results Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. Conclusions These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems.

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Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine

Cited by 27 publications

References 33 publications

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys

Buspirone maintenance does not alter the reinforcing, subjective, and cardiovascular effects of intranasal methamphetamine

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