Effects of buprenorphine/lorcaserin mixtures on preference for heroin, cocaine, or saline over food using a concurrent choice procedure in rhesus monkeys.

The opioid epidemic continues despite the availability of medications, including buprenorphine, for opioid use disorder (OUD); identifying novel and effective treatments is critical for decreasing the prevalence of OUD and ending this crisis. Buprenorphine alone does not markedly attenuate abuse-related effects of nonopioids. Treatment outcomes might be improved by combining buprenorphine with a second medication targeting substance use disorder (SUD), such as lorcaserin, a serotonin2C (5-HT2C) receptor selective agonist that decreases abuse-related effects of drugs from several pharmacological classes in preclinical studies. This study investigated the effectiveness of buprenorphine/lorcaserin mixtures to decrease preference for heroin or cocaine in monkeys choosing between food and i.v. infusions. When saline was available for self-administration, monkeys chose food; when heroin or cocaine was available, monkeys dose-dependently increased choice of infusions. Noncontingent administration of heroin, cocaine, or buprenorphine before sessions increased preference for saline over food. Daily noncontingent administration of buprenorphine increased saline choice, decreased heroin choice, and increased variability across monkeys and sessions; preference for cocaine was not altered. Adding lorcaserin to daily treatment reduced variability such that choice of saline and heroin was consistently less than 20%; choice of cocaine did not change. Because buprenorphine/lorcaserin mixtures would not likely alter abuse of cocaine, they might not be useful for treating SUDs; nevertheless, mixtures reduced variability and decreased preference for heroin, compared with buprenorphine alone, perhaps suggesting that a different drug mixture, in which buprenorphine is combined with a second, nonopioid drug, might offer advantages over treatment with buprenorphine alone.