How can we facilitate research on the risks and potential benefits of novel psychoactive substances?

Novel psychoactive substances (NPS) are synthetic compounds designed to mimic illicit drugs while circumventing international drug regulations. Commonly marketed as “research chemicals” or “legal highs”, these substances remain poorly understood, with limited evidence regarding their pharmacology, risks, and therapeutic potential. Current drug policies often place NPS in the strictest legal schedules, restricting the clinical and pharmacological research needed to assess both harms and possible medical benefits. This paper advocates for a public health-oriented regulatory framework that balances harm reduction with controlled scientific access. Existing clinical evidence indicates that some NPS present significant risks, whereas others may possess therapeutic value. To address this complexity, an evidence-based four-stage scheduling framework is proposed: Early Surveillance to identify emerging substances and harms; Provisional Scheduling to permit access to regulated research; Controlled Research to investigate pharmacology, safety, subjective and neurocognitive effects, abuse liability, and therapeutic potential; and Reclassification based on integrated clinical, toxicological, and public health evidence. This approach would reduce research barriers and support more adaptive, evidence-based regulation and more balanced drug policies.