title: Effects of acute oral naltrexone on the subjective and physiological effects of oral D-amphetamine and smoked cocaine in cocaine abusers.
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.
authors.affiliation: Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, and College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Shanthi
authors.initials: S
authors.lastname: Mogali
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Saccone
authors.forename: Paula
authors.initials: P
authors.lastname: Askalsky
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Walker
authors.forename: Jermaine D
authors.initials: JD
authors.lastname: Jones
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Vosburg
authors.forename: Ziva D
authors.initials: ZD
authors.lastname: Cooper
authors.forename: Perrine
authors.initials: P
authors.lastname: Roux
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Manubay
authors.forename: Eric
authors.initials: E
authors.lastname: Rubin
authors.forename: Abigail
authors.initials: A
authors.lastname: Pines
authors.forename: Emily L
authors.initials: EL
authors.lastname: Berkower
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002319:Cardiovascular System / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology*; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D012907:Smoking
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D009271:Naltrexone; D003042:Cocaine; D003913:Dextroamphetamine