Separate and combined effects of naltrexone and extended-release alprazolam on the reinforcing, subject-rated, and cardiovascular effects of methamphetamine

Katherine R. Marks; Joshua A. Lile; William W. Stoops; Paul E.A. Glaser; Lon R. Hays; Craig R. Rush

doi:10.1097/JCP.0000000000000488

Separate and combined effects of naltrexone and extended-release alprazolam on the reinforcing, subject-rated, and cardiovascular effects of methamphetamine

Katherine R. Marks, Joshua A. Lile, William W. Stoops, Paul E.A. Glaser, Lon R. Hays, Craig R. Rush

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, 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" subjectrated 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 to 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.

Original language	English
Pages (from-to)	213-221
Number of pages	9
Journal	Journal of Clinical Psychopharmacology
Volume	36
Issue number	3
DOIs	https://doi.org/10.1097/JCP.0000000000000488
State	Published - 2016

Bibliographical note

Funding Information:
This research and the preparation of the manuscript were supported by NIDA Grants R01 DA025591 (CRR), T32 DA035200 (CRR, KRM), K02 DA031766 (JAL), CTSA Grants UL1 TR000117 and TL1 TR000115 (KRM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study has been carried out in accordance with the Declaration of Helsinki. The authors declare no conflicts of interest relevant to this research.

Keywords

Alprazolam xr
Methamphetamine
Naltrexone
Self-administration

ASJC Scopus subject areas

Psychiatry and Mental health
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/JCP.0000000000000488

Cite this

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title = "Separate and combined effects of naltrexone and extended-release alprazolam on the reinforcing, subject-rated, and cardiovascular effects of methamphetamine",

abstract = "Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, 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{"} subjectrated 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 to 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.",

keywords = "Alprazolam xr, Methamphetamine, Naltrexone, Self-administration",

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note = "Funding Information: This research and the preparation of the manuscript were supported by NIDA Grants R01 DA025591 (CRR), T32 DA035200 (CRR, KRM), K02 DA031766 (JAL), CTSA Grants UL1 TR000117 and TL1 TR000115 (KRM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study has been carried out in accordance with the Declaration of Helsinki. The authors declare no conflicts of interest relevant to this research.",

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AU - Lile, Joshua A.

AU - Stoops, William W.

AU - Glaser, Paul E.A.

AU - Hays, Lon R.

AU - Rush, Craig R.

N1 - Funding Information: This research and the preparation of the manuscript were supported by NIDA Grants R01 DA025591 (CRR), T32 DA035200 (CRR, KRM), K02 DA031766 (JAL), CTSA Grants UL1 TR000117 and TL1 TR000115 (KRM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study has been carried out in accordance with the Declaration of Helsinki. The authors declare no conflicts of interest relevant to this research.

PY - 2016

Y1 - 2016

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AB - Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, 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" subjectrated 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 to 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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KW - Self-administration

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Separate and combined effects of naltrexone and extended-release alprazolam on the reinforcing, subject-rated, and cardiovascular effects of methamphetamine

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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