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.
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.
Greenwald
Mark K
MK
Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48207, USA. mgreen@med.wayne.edu
Lundahl
Leslie H
LH
Steinmiller
Caren L
CL
D000293:Adolescent; D000328:Adult; D002047:Buprenorphine / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000150:complications / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000150:complications / Q000188:drug therapy*; D012055:Reinforcement Schedule; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D002047:Buprenorphine; D003042:Cocaine; D004091:Hydromorphone; D003913:Dextroamphetamine