The combination of fentanyl and xylazine (i.e., “tranq-dope”) was recently declared an emerging national health threat in the United States. Given the recency of this development, very little is known regarding the behavioral pharmacology of fentanyl-xylazine combinations. The purpose of this study was to characterize the somatic and affective withdrawal symptoms of this drug combination.
Male and female Long Evans rats were given twice daily (08:00 and 20:00) subcutaneous injections of fentanyl, xylazine, or combined fentanyl-xylazine for five days. On the sixth (testing) day, rats were given a final injection at 08:00. Four hours later, rats were injected intraperitoneally with either saline or a naloxone challenge before behavioral observation. Somatic withdrawal was examined using the Gellert-Holtzman scale and anxiety-like behavior was examined using the elevated plus maze.
Naloxone administration did not induce somatic or affective symptoms in rats treated with fentanyl alone, a low dose of xylazine alone, or a high dose of xylazine alone. Naloxone induced somatic but not affective withdrawal symptoms in rats treated with both fentanyl and xylazine.
Chronic co-exposure to fentanyl and xylazine produces an opioid-like somatic withdrawal syndrome at doses that are not apparent with either drug alone. These results corroborate clinical reports that xylazine worsens fentanyl withdrawal and suggest that novel interventions may be required to treat withdrawal from fentanyl-xylazine combinations in humans.
The psychology of moral decision-making classically contrasts utilitarianism (based on consequences) and deontology (based on moral norms). Previous studies capitalizing on this dichotomy have suggested the presence of a utilitarian bias among patients with severe alcohol use disorder (SAUD). We aimed to further disentangle the processes involved in such bias through a more validated approach, the CNI model of moral decision-making. This model allows to go further than the classical approach by distinguishing sensitivity to consequences (C), to moral norms (N), and general preference for inaction over action (I) in response to moral dilemmas.
Thirty-four recently detoxified patients with SAUD and 34 matched control participants completed a battery of 48 dilemmas derived from the CNI model, as well as social cognition tasks.
In contrast with the utilitarian bias suggested in previous studies based on the classical approach, patients with SAUD did not show an increased sensitivity to consequences in comparison with control participants. However, they showed a reduced sensitivity to moral norms, as well as a greater action tendency. These biases were not related to social cognition deficits.
Patients with SAUD are not more utilitarian than healthy controls, this previously reported bias being artificially generated by the methodological limits of the classical approach. Instead, they present a reduced sensitivity to moral norms and an action bias, which might impact their interpersonal relations and contribute to the social isolation frequently reported in this population, thus identifying moral decision-making as a new therapeutic lever in SAUD.