Abstract
Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.
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Acknowledgements
We thank Drs Elias Dakwar, Abigail Herron, Nasir Naqvi, Rajkumar Kalapatapu, Taoi Huynh, and Alicia Murray for providing medical coverage during laboratory sessions and participant screening. In addition, we thank Janet Murray, RN and Claudia Tindall, RN, NP for providing nursing support during the study. The authors gratefully acknowledge NIDA for providing funding for this study (DA022222). NIDA had no role in study design or in the decision to submit the paper for publication. NIDA also had no role in the collection, analysis and interpretation of data in the writing of this report.
AUTHOR CONTRIBUTIONS
SD Comer, RW Foltin, and M Haney designed the study. SD Comer, S Mogali, A Pines, and EL Berkower wrote sections of the paper. PA Saccone and P Askalsky collected data and provided preliminary statistical analyses of the results. S Mogali, D Martinez, E Rubin, MA Sullivan, and JM Manubay provided medical coverage and/or medical advice during the study. SD Comer, ZD Cooper, JD Jones, P Roux, EA Walker, and SK Vosburg interviewed potential participants and supervised data collection. All of the co-authors read a draft of the paper.
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Portions of these data were presented at the 2011 and 2012 meetings of the College on Problems of Drug Dependence, as well as the 2011 meeting of the Colloque Europeen et International Toxicomanies Hepatites SIDA
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Comer, S., Mogali, S., Saccone, P. et al. Effects of Acute Oral Naltrexone on the Subjective and Physiological Effects of Oral D-Amphetamine and Smoked Cocaine in Cocaine Abusers. Neuropsychopharmacol 38, 2427–2438 (2013). https://doi.org/10.1038/npp.2013.143
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DOI: https://doi.org/10.1038/npp.2013.143
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