Figure 1.

Either a μ-opioid receptor partial agonist, a full 5-HT_2C receptor (5-HT_2CR) agonist, or a combination may afford gains in reducing relapse vulnerability and extending abstinence in opioid use disorder (OUD). Partial agonist actions at the μ-opioid receptor reduce the rewarding effects of opioids and withdrawal. The selective 5-HT_2CR full agonist lorcaserin suppresses oxycodone intake and associated cue reactivity as well as impulsivity. Low-dose combinations of a μ-opioid receptor partial agonist plus the non-opioid lorcaserin may provide an additional new avenue to support recovery in OUD patients. While the brain locus for a potential receptor–receptor interaction is unknown, both the μ-opioid receptor and 5-HT_2CR are co-expressed in nodes of the limbic-corticostriatal circuitry engaged in drug reward and relapse vulnerability. The FDA-approved OUD medication buprenorphine is a μ-opioid receptor partial agonist, but is not selective given its complex actions at δ-, κ-, and nociceptin/opioid receptor-like receptors (NOP or ORL-1) (Lutfy and Cowan, 2004). Thus, other μ-opioid partial agonists may be needed to test the hypothesis that low-dose combinations with lorcaserin may add value in OUD medication-assisted therapy.