Khatri, S., Sadek, S., Kendrick Jr., P.T., Bondy, E.O., Hong, M., Pauss, S., Luo, D., Prisinzano, T., Dunn, K.E., Marusich, J.A., Beckmann, J.S., Hinds Jr., T.D., Gipson, C.D. (in press). Xylazine co-use suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is naloxone-resistant in rats. Experimental and Clinical Psychopharmacology
Xylazine, a veterinary anesthetic, is becoming increasingly prevalent in the fentanyl drug supply within the United States, and opioid overdoses are on the rise, which is being attributed to xylazine’s adulteration of fentanyl. This is the first empirical publication demonstrating the impacts of intravenous xylazine on fentanyl self-administration and withdrawal as a function of xylazine dose and sex. This is also the first to quantitatively show that naloxone resistance occurs following xylazine/fentanyl co-use, and that these effects display a sex-specific trajectory whereby females are more susceptible to naloxone insensitivity and enhanced protracted withdrawal symptomatology following acute naloxone administration, which has enormous translational impact.