Jermaine D Jones1, Jeanne M Manubay2, Shanthi Mogali2, Verena E Metz2, Gabriela Madera2, Suky Martinez3, Mudassir Mumtaz3, Sandra D Comer2. 1. Division on Substance Use Disorders, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. Electronic address: Jermaine.Jones@NYSPI.Columbia.edu. 2. Division on Substance Use Disorders, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. 3. Division on Substance Use Disorders, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA; Translational Research Training Program in Addiction, City College of New York, 160 Convent Avenue, New York, NY 10031, USA.
Abstract
BACKGROUND: This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects. METHODS:Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively. RESULTS: IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition. CONCLUSIONS: This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.
RCT Entities:
BACKGROUND: This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects. METHODS:Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively. RESULTS: IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition. CONCLUSIONS: This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.