Federal Project Grant Award Summary

The National Institute on Drug Abuse (NIDA) awarded the University of Pittsburgh $434,005 on May 15, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to conduct research on countering xylazine damage through natural products targeting cholinergic receptors. The project, which extends through April 30, 2028, addresses a critical public health gap by investigating the pharmacological mechanisms of xylazine—an increasingly prevalent adulterant in illicit opioid supplies for which no FDA-approved reversal medications currently exist. The research will identify additional receptor targets beyond alpha-2 adrenergic receptors through which xylazine exerts harmful effects, characterize the functional consequences and immune responses resulting from xylazine exposure, and develop effective countermeasures using naturally derived compounds that are proven safe for human use.

The deliverables from this R21 Exploratory/Developmental Grant include scientific findings on xylazine's inhibition of alpha-7 nicotinic acetylcholine receptors (α7nAChRs) and investigation of how natural products can offset this inhibition across different human cell types. Preliminary data indicate that xylazine's widespread damage—ranging from central nervous system depression to severe skin lesions and infection—likely results from its action on multiple receptor targets, particularly the calcium-conducting α7nAChRs critical to cholinergic anti-inflammatory pathways. The research will generate new knowledge to inform the development of clinical interventions for xylazine-related harm in the context of the ongoing opioid and emerging xylazine misuse epidemic.