Is there enough naloxone to deter the diversion? Effect of concurrent administration of intravenous naloxone on opioid agonist effects of intravenous buprenorphine: A randomised, double-blind, within-subject, crossover study among opioid-dependent subjects.

Abstract

We aimed to evaluate and compare the effect of different intravenous doses of naloxone on reinforcing effect of intravenous buprenorphine (2 mg) in patients stabilised on sublingual buprenorphine. This is a double-blind, within-subject, randomised, crossover study. Opioid-dependent patients, with history of intravenous drug use, stabilised on buprenorphine maintenance treatment were included after informed consent (n = 14). We administered and assessed the reinforcing effects of six test conditions: buprenorphine and naloxone co-formulation (BNX) in 4:1, 2:1 and 1:1 dose ratio (i.e. buprenorphine 2 mg + naloxone 0.5, 1 and 2 mg, respectively), buprenorphine alone (2 mg), pheniramine maleate (45.5 mg) and saline at 24 hourly intervals. No significant opioid withdrawals were precipitated during any test conditions. Compared to buprenorphine alone, 4:1 BNX had comparable euphoria, drug recognition, subjective opiate sensations and drug liking (P > 0.05); 2:1 BNX condition had significantly different subjective euphoria (P = 0.001), opioid recognition (P = 0.002), subjective opioid sensations at 60 min (P = 0.027) and drug liking (P < 0.001), while 1:1 BNX had significantly different objective euphoria (P = 0.002), opioid recognition (P = 0.030), subjective opioid sensations (P < 0.001) and drug liking (P < 0.001). No significant difference was noted on sedation scores between buprenorphine alone and all three combinations of BNX. The 4:1 BNX condition did not impact the reinforcing agonist effects of buprenorphine. None of the intravenous BNX combination ratios precipitated opioid withdrawals. Findings emphasise the need for exploring more abuse deterrent mechanisms.