Treatment of Co-Occurring Methamphetamine and Opioid Use Disorders

Stimulants are the drivers of the fourth wave of the US drug overdose epidemic. Although most national attention and resources have been targeted at combating opioid use due to the surge of deaths related to fentanyl, recent reports suggest populations that use opioids are also using methamphetamine (MA) at high rates. Indeed, current data show that as many opioid overdose deaths involved psychostimulants as did not. These epidemiological data underscore the significance of developing efficacious treatments for methamphetamine use disorder (MUD) – especially in the setting of ongoing opioid use. Most therapeutic trials for MUD have failed with a few exceptions. Two randomized controlled trials (RCTs) showed that 30 mg of mirtazapine reduced MA use by 27% at week 36. A recent RCT completed by the clinical trials network (CTN) tested injectable naltrexone plus high-dose oral bupropion 450 mg/day compared to placebo and reported statistically significant reductions in methamphetamine use in a broad sample of people with MUD. This combination pharmacotherapy is impossible to use among those who use opioids as the opioid antagonist naltrexone precipitates immediate opioid withdrawal, further underscoring the need for a pharmacotherapy strategy without an opioid antagonist. As a monotherapy, buprenorphine (BUP) has sufficient rationale for evaluation as a medication for MUD in the setting of opioid co-use. Findings from another CTN study showed that extended-release Naltrexone plus oral BUP, produced modest, though statistically significant, reductions in cocaine use among those adherent to oral BUP. These findings provide initial support for a kappa antagonist approach to treating MUD, as the combination pharmacotherapy leaves only a kappa antagonist working at the opioid receptor. While there are no placebo-controlled RCTs of Bup for MUD, a recent clinical report showed patients treated for OUD using Bup showed a 15% reduction in MA use from baseline to follow-up.

Learning Objectives:

1. Demonstrate an understanding of the definition and epidemiology of stimulant use disorder, especially in the context of co-opioid use.

2. Describe the neurobiology in development and maintenance of stimulant use disorder and how this relates to treatment outcomes.

3. Review evidence for advancements in pharmacotherapies that can be brought into practice.