Separate and concurrent use of methamphetamine and fentanyl: behavioral and neurobiological consequences

Background Methamphetamine, a potent psychostimulant, is one of the most used substances globally. When administered alone, methamphetamine has powerful rewarding and reinforcing properties and produces numerous health consequences. However, recent national trends reveal that methamphetamine is increasingly being used concurrently with fentanyl. Of particular concern is that many methamphetamine users are unwittingly exposed to fentanyl, due to the increasing rate at which psychostimulants are “laced” with the opioid. While the amplified health risks of the drug combination, such as potential overdoses, are well documented, their shared addictive potential is less clear. Methods In this review, we assessed the current literature on the neurobiological mechanisms associated with concurrent methamphetamine and fentanyl use, as well as the behavioral effects of the combined drugs. Results Agonism of μ opioid receptors is a critical system involved in modulating the behavioral effects of methamphetamine and fentanyl, including conditioned place preference, cue-reactivity and behavioral sensitization. The existing literature also suggests that methamphetamine and fentanyl may have synergistic interactions that enhance their addictive potential, effects that are likely mediated by μ opioid receptors. Conclusion Concurrent methamphetamine-fentanyl use is a mounting crisis. Unfortunately, the neurobiological and behavioral consequences of this drug combination have not been adequately examined. While the existing literature on concurrent methamphetamine-opioid use indicates that the drugs have synergistic addictive potential, more research specifically examining methamphetamine-fentanyl combinations is needed.