Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety

Abstract

Withdrawal syndrome is one of the initial focuses of opioid detoxification. Very low dose naltrexone (VLNTX) has been found to reduce opioid tolerance and dependence in animal and human clinical studies. The aim of this study was to determine the safety and efficacy of VLNTX during early stages of detoxification. In a multi-arm parallel, double-blind, randomized controlled trial, 63 opioid-dependent male participants referring to Imam Reza Rehabilitation Center were allocated to three equal groups using block randomization method. They received 0.125 mg, 0.250 mg of VLNTX or placebo daily for 10 days, together with the routine clonidine-based protocol. Self-reported and observer ratings of withdrawal severity and adverse events were measured on the 1st, 4th and 10th day of treatment. Runny eyes (p = 0.006), anxiety (p = 0.031) and dehydration (p = 0.014) were reduced during the whole 10 days in the 0.125 mg VLNTX-treated group compared to placebo. Only drowsiness (p = 0.043) and dysphoric mood (p < 0.001) were reduced in the 0.250 mg VLNTX-treated group. Results of 1st, 4th, and 10th-day assessment showed that most symptoms reductions were for the 0.125 mg VLNTX and the placebo group in the 1st and 4th days, respectively. On the 10th day, there was not any significant difference between 0.250 mg VLNTX-treated group and placebo group. No adverse effect was observed. In the starting days of detoxification, VLNTX can reduce the withdrawal symptoms, but the efficacy declined by passing time. Further studies are needed to test the utility of this new therapeutic approach.

Keywords: Metabolic detoxification; Naltrexone; Opioid; Substance withdrawal syndrome.

Fig. 1

Flow diagram of study design

Fig. 2

Mean (SE) severity score in 3 days of observation in three interventional groups (n = 21 in each group)