Abstract
The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball’ (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.
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Acknowledgements
NIH Grant R01 DA022243 from the National Institute on Drug Abuse and a research grant (Joe Young, Sr. funds) from the State of Michigan supported this research. This study was registered as NIH Clinical Trial NCT00429767 (http://clinicaltrials.gov/ct2/show/NCT00429767). We thank Dr Chris-Ellyn Johanson for consultation, Dr Carl Christensen for medical oversight, Ken Bates for recruitment, and Debra Kish, Joi Moore, and Lisa Sulkowski for data collection and management. We thank the staff of the Psychiatric and Addiction Research Center at Wayne State University for clinical data collection and safety monitoring.
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The authors declare no conflicts of interest in relationship to performing this study. Dr Greenwald has received compensation as a consultant to Reckitt-Benckiser Pharmaceuticals, the company that markets the buprenorphine products, Suboxone and Subutex. Both Dr Greenwald and Dr Steinmiller have received compensation from Titan Pharmaceuticals. Dr Lundahl has received compensation from Gateway Community Health (Michigan), and the National Football League.
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Greenwald, M., Lundahl, L. & Steinmiller, C. Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers. Neuropsychopharmacol 35, 2624–2637 (2010). https://doi.org/10.1038/npp.2010.175
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