Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

Abstract

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

Structure-based design of glycosylated oxytocin analogues with improved selectivity and antinociceptive activity

“…Exogenous OT administration has been shown to mitigate classical addiction metrics, including selfadministration, withdrawal and tolerance. [14][15][16][17]60 More recently, clinical trials have lacked consistency and yielded mixed results, 14 though strong evidence indicates that intranasal administration of OT leads to increased compliance with therapeutic interventions, addressing a well-established barrier to effective OUD/SUD treatment. OT was found to be a safe, effective attenuation for nonopioid respiratory depression in patients at increased risk for OIRD.…”

“…13 OT has also been evaluated for analgesia in humans, 9,12 with studies showing mixed results, at least partly due to design inconsistencies. [14][15][16][17] Unfortunately, OT remains a poor drug candidate. 10,18 Debate over its effective BBB penetration has persisted, although recent evidence indicates success.…”

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity

“…An important consideration of novel pain therapeutics is avoidance of negative opioid side effects, including reinforcing behavior, and oxytocin (OT) has been investigated as a potential OUD treatment in animals. Exogenous OT administration has been shown to mitigate classical addiction metrics, including self-administration, withdrawal, and tolerance. − More recently, clinical trials have lacked consistency and yielded mixed results, though strong evidence indicates that intranasal administration of OT leads to increased compliance with therapeutic interventions, addressing a well-established barrier to effective OUD/SUD treatment. Thus, OT was found to be a safe, effective attenuation for nonopioid respiratory depression in patients at increased risk for OIRD. , Cardiorespiratory depression caused by fentanyl in rats was dose-dependently reversed by OTR activation, both with OT and with a nonpeptide partial agonist in a recent study by Brackley et al…”

“…11 OT has also shown mixed results for analgesia in humans, 9,16 at least partly due to design inconsistencies. 12,13,18,19 Unfortunately, OT itself remains a poor drug candidate. 14,20 Debate over its effective BBB penetration has persisted, although recent evidence indicates success.…”

“…Oxytocin has been investigated for treating pain for three decades in both animals and humans. ,− Most of these studies showed administration-independent antinociceptive effects (i.e., systemic, peripheral, intrathecal, intracerebroventicular, intranasal, i.v., or inhaled vapor administration); fewer studies showed no significant antinociception . OT has also shown mixed results for analgesia in humans, , at least partly due to design inconsistencies. ,,, …”