The impact of opioid-stimulant co-use on tonic and cue-induced craving

The twin opioid-stimulant epidemics have led to increased overdose deaths and present unique challenges for individuals entering treatment with opioid-stimulant polysubstance use. This study examined tonic and cue-induced craving as a primary outcome among persons in substance use treatment who reported primary substances of opioids, methamphetamine, or cocaine. The sample consisted of 1974 individuals in 55 residential substance-use treatment centers in the United States in 2021. Weekly surveys were delivered via a third-party outcomes tracking system, including measures of tonic and cue-induced craving. Initial comparisons on tonic and cue-induced craving were made among those who primarily used opioids, cocaine, or methamphetamine. Further, the effect of opioid/stimulant polysubstance use on tonic and cue-induced craving was evaluated using marginal effect regression models. Primary methamphetamine use was associated with decreased tonic craving compared to primary opioid use (β = -5.63, p < 0.001) and primary cocaine use was also associate with decreased tonic craving compared to primary opioid use (β = -6.14, p < 0.001). Primary cocaine use was also associated with lower cue-induced cravings compared to primary opioid use (β = -0.53, p = 0.037). Opioid-methamphetamine polysubstance use was associated with higher tonic craving (β = 3.81, p = <0.001) and higher cue-induced craving (β = 1.55, p = 0.001); however, this was not the case for opioid-cocaine polysubstance use. The results of this study indicate that individuals who primarily use opioids and have secondary methamphetamine use experience higher cue-induced and tonic-induced craving, suggesting that these individuals may benefit from additional interventions that target craving and mitigate relapse risk and other negative sequelae.