Naltrexone-bupropion combinations do not affect cocaine self-administration in humans

Area of Science:

• Pharmacology
• Addiction Medicine
• Clinical Psychology

Background:

• Despite decades of research, no FDA-approved pharmacotherapy exists for cocaine use disorder.
• Naltrexone and bupropion are individually being investigated for substance use disorders.
• Combination therapies may offer synergistic benefits for treating complex addictions.

Purpose of the Study:

• To determine the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations for cocaine use disorder.
• To assess the impact of combined naltrexone and bupropion on cocaine self-administration.
• To evaluate subjective and cardiovascular effects of cocaine under combined pharmacotherapy.

Main Methods:

• A mixed-design human laboratory study with 31 non-treatment seeking participants with cocaine use disorder.
• Random assignment to naltrexone (0, 50 mg/day) and escalating bupropion doses (0, 100, 200, 400 mg/day).
• Cocaine self-administration assessed using a modified progressive ratio and relapse procedure; subjective and cardiovascular effects measured.

Main Results:

• Cocaine increased self-administration and subjective/cardiovascular effects during placebo maintenance.
• Naltrexone and bupropion, alone or combined, did not significantly reduce cocaine self-administration.
• Low-dose bupropion (100 mg) blunted subjective "Like Drug" and "Stimulated" effects of cocaine.

Conclusions:

• The tested naltrexone-bupropion combinations do not support their use for treating cocaine use disorder.
• No unexpected adverse effects were observed with the combined pharmacotherapy and cocaine.
• Future research should explore novel drug combinations for reducing cocaine self-administration.