Thread by @nabarund

Does naloxone help with xylazine-heroin-fentanyl overdose? Great question from @JessTilley7

Thread below on what we do and don't know from the scientific lit with @mary_figgatt @WeezieBeale @nc_USU

Would love @VetFinals to provide clinical insight too

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 2. At issue is this flyer where we say "Naloxone works on opioids. It may work on xylazine, but the evidence is unclear. Always use naloxone in the event of an overdose."

https://twitter.com/nabarund/status/1381694109216165891?s=20

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 3. Xylazine is called a "sedative" but is in a different pharmacological family from benzodiazepines. It is not an opioid. It's legit to think naloxone might work on xylazine alone. So let's unpack that from the perspectives of pharmacology, veterinary med, and street drugs.

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 4. The key point is that all xylazine in NC drug samples we tested had been mixed with opioids like fentanyl, and sold as heroin/fentanyl. So, until we see xylazine showing up alone, our rec is to use naloxone to at least overcome *opioid-induced* respiratory depression.

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 5. Universal co-occurrence of xylazine and opioids was also reported in Connecticut in a fresh report just published.

"Fentanyl was detected in all xylazine-positive deaths, and heroin was detected in half of them."
pubmed.ncbi.nlm.nih.gov/33031124/

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 6. In veterinary medicine, xylazine is usually used in conjunction with other immobilizing drugs. For example, this study on carfentanil+xylazine in elk shows quick recovery with IM naloxone alone.

jstor.org/stable/20095163

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 7. Considering alt hypotheses here since human xylzaine-OD-naloxone info is limited. In one report where someone drank a suicidal dose of xylazine and nothing else, 2mg IV naloxone didn't do anything. (unlike heroin-xylzaine mixtures we are seeing now)

https://twitter.com/nabarund/status/1375092545055756291?s=20

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 8. OD from snorting Xylzaine (dried on a CD case!) and drinking alcohol was also unresponsive to naloxone. (unlike heroin-xylzaine mixtures we are seeing now)
journals.lww.com/pec-online/Abs…

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 9. Animal data: Mice tail-flick studies show some xylazine-alone effects aren't reversed by naloxone, and naloxone doesn't prevent xylazine-induced vomiting. But again, no opioid here and not looking at respiratory depression.

pubmed.ncbi.nlm.nih.gov/6113017/

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 10. Ready? This is where it gets wild. In a 1984 study, naloxone reversed sedation in chicks 🐔. Yes, as in chickens.
Is this an outlier experiment? Primate vs. avian limbic system? Body volume effects? Exogenous vs. endogenous opioids?

pubmed.ncbi.nlm.nih.gov/6144554

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 11. "These findings suggest that in addition to the stimulation of central alpha 2-adrenoceptors, activation of an endogenous opiate mechanism may be involved in the sedative effect of xylazine."

pubmed.ncbi.nlm.nih.gov/6144554

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 11. Beyond xylazine, naloxone appears to have (weak) antagonistic effects via non mu-opioid receptor pathways. But these are very poorly studied, so the street adage that "naloxone only works on opioids" is still valid for all practical messaging purposes. Don't change!

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 13. So, given that xylazine is currently only seen in the presence of heroin-fentanyl & science ambiguity, our intentionally worded statement is: "Naloxone works on opioids. It may work on xylazine, but the evidence is unclear. Always use naloxone in the event of an overdose."

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals 14. Someday we will look at street drug analysis as a way to improve health rather than to put people in cages. The exclusive medico-legal focus on "controlled substances" and addiction means that health harms from the other components of dope are a @NIDAnews afterthought

@JessTilley7 @mary_figgatt @WeezieBeale @nc_usu @VetFinals @NIDAnews 15. Hope that helps lay the foundation for further discussion. What we really need to hear are PWUD experiences using naloxone in recent ODs from areas with consistent xylazine in dope, or FTIR-confirmed xylazine!! Many thanks to @JessTilley7 for inspiring this!
/end

Sorry that should read: It’s legit to think that naloxone MAY NOT WORK on xylazine alone. My bad