New from ADAI: Fentanyl, Meth Use Impact Behavior in Rats; Psychedelic Treatment Reverses Social Deficits
03/11/2026
Drug overdose deaths in the United States have skyrocketed over the last 20 years, and an increasing number of those deaths now involve people using multiple substances, particularly opioids and stimulants.
Despite how common this combination has become, most research has looked at these substances separately, leaving a major gap in our understanding of what happens in the brain and body when people use them together.
Researchers at the University of Washington, including ADAI’s director Susan Ferguson, PhD, set out to address this gap by studying rats given fentanyl, methamphetamine, or both, and observing how each scenario affected their behavior.
The study looked at two key outcomes: how the drugs affected physical activity over time, which is used as a proxy for changes in the brain circuits that regulate addiction, and how they affected social behavior after the rats stopped taking the drugs.
Impact on physical activity
The researchers found that fentanyl, either given alone or with methamphetamine, caused the rats to become increasingly hyperactive with each dose, a sign of the brain adapting to the drug.
Methamphetamine’s effects were more complex and differed between male and female rats. Using both drugs together did not increase activity beyond what was seen with methamphetamine alone.
Impact on social behavior
Only the rats that had received both drugs showed a significant drop in interest in socializing with other rats during withdrawal, suggesting that the combination uniquely harms social functioning in ways that single drug use doesn’t.
Psychedelics as a potential treatment for social withdrawal
After the withdrawal period, the researchers gave the rats a single dose of a psychedelic compound called DOI before testing their social behavior again. The rats that had been using both fentanyl and methamphetamine, and had lost interest in socializing, returned to normal social behavior after just one dose of DOI. Rats that received a placebo instead showed no such recovery.
Although these findings are from an animal study, they suggest that psychedelic compounds could one day help address the social withdrawal and isolation that often accompany polysubstance addiction, highlighting a promising direction for future research.
Citation: Salinsky LM, et al. Fentanyl, methamphetamine and polysubstance use differentially affect locomotor sensitization and social behaviour in rats: Psychedelic treatment reverses social deficits. Addiction Biology 2026;31(3):e70132.
