This bill amends the Controlled Substances Act to address the proliferation of synthetic opioids. It mandates that all fentanyl-related substances be listed as Schedule I controlled substances, subjecting them to the highest level of federal control and penalties. The legislation provides a comprehensive definition of "fentanyl-related substances" by detailing specific structural modifications to the fentanyl molecule. These modifications include replacements or substitutions on the phenyl, phenethyl, piperidine ring, aniline ring, or N-propionyl groups. This broad definition aims to proactively control new fentanyl analogues as they emerge, thereby strengthening efforts to combat overdose deaths.