Opioid Use Disorder
Opioid use disorder (OUD) is a chronic, relapsing condition characterized by compulsive opioid use despite adverse consequences. Over 105,000 people in the US have died from drug-induced overdose in 2023, including 72,776 due to synthetic opioids, primarily fentanyl.[1, 2] While deaths due to heroin and prescription opioids have fallen in recent years, deaths caused by fentanyl and other highly potent synthetic opioids, either alone or combined with heroin, xylazine, cocaine, or methamphetamine have increased dramatically both in the United States and worldwide. [3, 4] Nitazenes, first developed in the 1950s as alternative pain relievers to morphine but never approved for medical use, have re-emerged in the illicit drug supply and are up to 43x more potent than fentanyl. [5] Nitazenes are increasingly a component of street opioid mixtures and counterfeit pills, further contributing to the rise in opioid overdose deaths. [6] ​
Another troubling trend in recent years has been the inclusion of the animal tranquilizer xylazine in street opioid mixtures. Xylazine is a alpha2-adrenergic agonist used as a veterinary non-opioid sedative, analgesic, and muscle relaxant. In a combination commonly referred to as “Tranq-dope”, xylazine is added as an adulterant to street opioid preparations in order to potentiate and prolong the effects of the opioid. This combination can dramatically raise the risk of coma or death. [7] Additionally, the vasoconstrictive action of xylazine is implicated in the development chronic soft tissue infections in the distal extremities. [8, 9] Existing and emerging polydrug combinations pose an evolving threat not only to people with OUD who may more easily overdose, but also to first responders, who may become inadvertently exposed.
Design-Zyme’s Solution for OUD
OUD vaccines targeting heroin, morphine, oxycodone, hydrocodone, or fentanyl have shown promising efficacy by using specifically designed haptens that induce potent antibody responses.[10, 11] These antibodies effectively reduce the distribution of opioids to the brain when they are administered effectively blunting or eliminating drug effects. These vaccines have been shown to decrease opioid-induced effects and increase survival rates against lethal doses.[12] Because many individuals with OUD often are exposed to multiple opioids or other substances concurrently as part of street-drug mixtures, multivalent vaccines that target multiple street drugs offer superior protection. Design-Zyme has developed a novel trivalent vaccine, DZ-XNF1, that targets xylazine, nitazenes, and fentanyl. The vaccine elicits high, durable antibody titers and demonstrates physiological protection against all three of these commonly abused drugs lasting over one year.
DZ-XNF1
Concept drawing of DZ-XNF1
DZ-XNF1 Advantages
References
1. CDC (2021) Available from: www.cdc.gov/drugoverdose/deaths/.
2. NIDA (2024) Available from: https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates.
3. Ciccarone, D. (2021) 10.1097/YCO.0000000000000717
4. Patocka, J., et al. (2024) 10.1016/j.heliyon.2024.e28795
5. Pergolizzi, J., Jr., et al. (2023) 10.7759/cureus.40736
6. Vandeputte, M.M., et al. (2024) 10.1016/j.phrs.2024.107503
7. Smith, M.A., et al. (2023) 10.3389/fphar.2023.1280289
8. Edinoff, A.N., et al. (2024) 10.1007/s11916-024-01211-z
9. Marshall, S.A., et al. (2025) 10.1177/08971900241279635
10. Pravetoni, M., et al. (2019) 10.1016/j.neuropharm.2019.06.001
11. Baehr, C., et al. (2025) 10.1021/acs.bioconjchem.4c00548
12. Tuncturk, M., et al. (2025) 10.1093/ijnp/pyaf005