Illicitly-manufactured fentanyls and synthetic opioids are unregulated, so they are of unknown composition and potency. That can make it difficult to determine appropriate dosage to avoid unintentional overdose and other harms.

Many are highly potent with effects active at much lower doses (around 1-2 nanograms or less) than other opiates.

When added to other unregulated drugs like heroin or counterfeit prescription opioids, illicitly-manufactured fentanyls and other synthetic opioids can increase overdose risk dramatically. They can cause sedation and suppress breathing very rapidly so even those with a tolerance for heroin are at risk. The risk is even greater for opioid-naïve users.

Some synthetic opioids are known only by their chemical shorthand, such as W-18, U-47700, and AH-7921. Potency and effects can vary widely among these substances, and short and long term health risks are not always clearly known because they are difficult to study and are often emerging in drug markets faster than they can be tracked.