Addiction Science Made Easy
October 2023
CTN Dissemination Library & Northwest ATTC
In the U.S., the proportion of people with opioid use disorder (OUD) who also report using stimulants (typically methamphetamine or cocaine) has increased dramatically over the past 20 years.
These increases are closely connected to the overdose epidemic that is now responsible for over 100,000 deaths a year. According to the National Institute on Drug Abuse (NIDA), fatal overdoses involving both cocaine and opioids increased 5.6-fold between 1999 and 2019, and fatal overdose involving both “psychostimulants with abuse potential,” a category dominated by methamphetamine, and opioids increased 13.5-fold.
Co-use of methamphetamine and synthetic opioids like fentanyl is likely to be even deadlier: emerging data from the beginning of the COVID-19 epidemic showed deaths involving both substances doubling in a single year.
Numerous randomized controlled trials have established that medications for opioid use disorder (MOUD) are effective for the treatment of OUD. Despite their efficacy, though, people treated with MOUD sometimes return to illicit opioid use. Treatment options for stimulant use disorder are much more limited – though behavioral interventions like contingency management have been shown to be effective, they can be difficult to implement, and there are currently no medication treatments available.
People who use both stimulants and opioids face unique challenges. Some use stimulants to counteract some effects of opioids (e.g., to stay awake or to try to prevent or reverse an overdose), others use opioids to manage the side effects of stimulants (e.g., to lessen the “come-down” or to fall asleep). People used to using both substances may find it harder to quit using opioids because use of stimulants acts as a trigger, making them crave opioids.
To date, there’s been little research on the impact of stimulant use on retention in MOUD treatment. Does stimulant use really increase risk of relapse to opioid use? Does one medication for OUD work better than another at preventing that return to use in someone who is still using stimulants? What else can we learn about the challenges faced by people who use both substances?
Gaining a better understanding of this specific combination of substance co-use could help clinicians and counselors better support people seeking to stop use of one or both.
This study used data from two NIDA Clinical Trials Network studies (CTN-0051 and CTN-0067) designed to compare the effectiveness of two MOUDs: extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (NUP-NX). Researchers wanted to learn more about the relationship between continued stimulant use following initiation to MOUD treatment so they dug through the datasets to look for two things: 1. How long it took someone to use any non-prescribed opioids again after starting on MOUD, and 2. Subsequent risk of relapse to ongoing opioid use.
Their theory was that, because it’s a long-acting full opioid antagonist (meaning it fully blocks the effects of opioids), XR-NTX would be more effective that BUP-NX in preventing return to opioid use in someone still using stimulants.
Based on the data, stimulant use after starting on MOUD appeared to substantially increase the risk of return to illicit opioid use: using stimulants on a given day was associated with a 9-fold increase in the risk of returning to opioid use that same day, with risk increasing as stimulant use continued.
Additionally, among participants who used non-prescribed opioids after starting treatment, those who were also using stimulants at least once a week were substantially more likely to relapse to ongoing illicit opioid use.
Though the risk of return to use was elevated for people using either type of MOUD, it was substantially higher for those taking BUP-NX compared to those taking XR-NTX for their OUD.
This study provides strong evidence that ongoing stimulant use puts recovery from opioid use disorder at risk. The reasons for this, however, remain unclear. Is it the stimulants themselves? Is it that people who use both substances have more severe substance use disorders (SUDs) to begin with and therefore have a greater risk for relapse than people with less severe SUDs? Regardless of the answers to these questions, which still need to be explored through more research, these results suggest that people who are engaging in MOUD treatment while also using stimulants might benefit from more intensive clinical and behavioral support.
It's also important to note that while XR-NTX was found to be more effective at preventing return to illicit opioid use in stimulant-using participants than BUP-NX, the reasons for that are also unclear. However, co-use of opioids and stimulants might be one reason to opt for XR-NTX over BUP-NX for a given patient. Efforts to identify effective treatments for stimulant use disorders and integrate these treatments with treatment for OUD should be intensified to help better support this population.