Effects of lorcaserin on oxycodone self-administration and subjective responses in participants with opioid use disorder

Abstract

Background: Lorcaserin, a high-affinity 5-HT_2C receptor agonist approved for treating obesity, decreased self-administration of oxycodone and cue-induced reinstatement of drug-seeking behavior in preclinical studies. The current investigation is the first clinical trial to evaluate the ability of lorcaserin to alter the reinforcing and subjective effects of oxycodone.

Methods: In this 7-week inpatient trial, 12 non-treatment-seeking volunteers (11 males) with moderate-to-severe opioid use disorder were detoxified from opioids. In a randomized cross-over fashion, participants were first stabilized on lorcaserin (10 mg BID) or placebo (0 mg BID). Participants underwent a two-week testing period during which the reinforcing and subjective effects of intranasal oxycodone were examined in verbal choice, cue-exposure, and progressive-ratio choice sessions. The two testing weeks were identical with the exception that during the first week, active oxycodone (10 mg) was available during verbal choice (self-administration) sessions, and during the second week placebo oxycodone was available. Subsequently, participants were stabilized on the other medication condition (placebo or lorcaserin) and underwent the same testing procedures again.

Results: Lorcaserin did not alter oxycodone self-administration. However, lorcaserin had a trend to increase "wanting heroin" when oxycodone was available, and to accentuate oxycodone-induced miosis.

Conclusion: Under the current experimental conditions, lorcaserin at a dose of 10 mg BID did not reliably decrease the abuse liability of oxycodone, even though the study was sufficiently powered (≥80 %) to detect clinically meaningful differences in the main outcome variables between the placebo and active lorcaserin condition. Future research could explore a wider dose range of lorcaserin and oxycodone.

Keywords: Lorcaserin; Opioid use disorder; Oxycodone; Self-Administration; Subjective effects.

Figure 1.

Panel A: Drug (oxycodone or placebo) versus money ($10) self-administration in the active lorcaserin (10 mg BID; closed circles) versus the placebo lorcaserin (0 mg BID; open circles) condition assessed using a verbal choice procedure during Days 1–4. Panel B: Oxycodone (10 mg) self-administration using a progressive-ratio procedure (Day 5) in the active lorcaserin (10 mg BID; closed circles) versus the placebo lorcaserin (0 mg BID; open circles) condition following 4 days of access to placebo oxycodone or active oxycodone.

Figure 2.

Mean pupil diameter (panel A), mean systolic pressure (panel B) and mean diastolic pressure (panel C) after administration of placebo oxycodone (0 mg) or active oxycodone (10 mg) on the sample session days (Day 1) in the active lorcaserin (10 mg BID; closed circles) versus the placebo lorcaserin (0 mg BID; open circles) condition. PBO lorcaserin vs active lorcaserin: *p<0.01, **p<0.001