The proliferation of new psychoactive substances (NPS), including synthetic cannabinoids, is challenging regulatory systems and public health worldwide. Unlike conventional drugs, NPS often lack established safety profiles and pose unpredictable health risks, including severe toxicity and adverse reactions. Designed to mimic the effects of strictly regulated illicit drugs, NPS evade legal classification through ongoing compound diversification through molecular alterations. The availability of NPS online is increasing the difficulty of monitoring and controlling their market distribution.
The rapid emergence of NPS is driving a need for faster classification methods to support assessing the safety, toxicity, and carcinogenic potential of these substances. In response, researchers at Linköping University, in collaboration with the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine (NBFM), have developed a new risk assessment strategy. As part of this, Tecan’s Spark® multi-mode plate reader was used as part of in vitro receptor activity assays to assess drug functionality and demonstrate neurological activity of NPS. Spark, was used to advance the screening methods on synthetic cannabinoids, increasing both speed and accuracy. These efforts are informing PHAS's evidence-based regulatory measures and help mitigate the public health risks associated with thesesubstances.
The Challenge of Synthetic Cannabinoids and the Need for a Rapid Screening Method
It is the structural diversity and dynamic evolution of synthetic cannabinoids that complicates their monitoring and classification, posing an increasing challenge to regulatory efforts. Henrik Green, professor of forensic sciences at the department of biomedical and clinical sciences at Linköping University and researcher at the National Board of Forensic Medicine, explained this issue stating, “The characteristics of NPS, particularly synthetic cannabinoids, have contributed to their proliferation, exacerbating public health risks with unpredictable effects. This was the driver behind our work with PHAS and NBFM – we needed to develop a method that could quickly and accurately measure the pharmacological effects of these substances.”
Henrik Green, professor of forensic sciences at the department of biomedical and clinical sciences at Linköping University and researcher at the National Board of Forensic Medicine
The goal of the collaboration was to enhance public safety by providing a tool that regulatory agencies could use to swiftly characterize and eventually control NPS. Rapid classification is particularly needed in Sweden where substances are scheduled as narcotics based on the exact chemical structure of the compound. In some other countries entire drug groups are scheduled based on a common chemical structure or mechanism of action.
Impact and Effectiveness of Screening in Identifying and Regulating Psychoactive Cannabinoids
Tecan’s multi-mode plate reader, Spark, was used to advance the screening methods on synthetic cannabinoids, increasing both speed and accuracy. Using Spark, researchers determined receptor activation at varying drug concentrations, providing insights into drug effects. Sensitivity and automation provided by Spark were crucial for understanding the impacts of synthetic cannabinoids on biological systems. Henrik emphasized, “The Spark’s precision and high throughput capabilities were essential for the rapid and precise evaluation of drug effects in our studies.”
Analysis for Cannabinoid receptor 1 (CB1) activity of 17 suspected psychoactive cannabinoid drugs, present on the drug market, was carried out to obtain insights into their effects and risks. Henrik explained, "The new method uses high-throughput screening technology to assess the activation of cannabinoid receptors by various substances. By measuring receptor activation levels at different drug concentrations, we could quickly determine the psychoactive potential and toxicity of each compound.”
The analysis showed that 15 substances demonstrated CB1 receptor activation resulting in 14 of those being scheduled as narcotics in Sweden. These results provided crucial pharmacological data to support their classification under Swedish narcotic legislation.Henrik commented, “These findings underscore the need for rapid and accurate screening methods to identify and control such dangerous substances."
Accelerated classification has prevented potential health crises as authorities can quickly identify and ban hazardous synthetic cannabinoids. Henrik added, "There have been instances where our classification method identified particularly dangerous synthetic cannabinoids early, allowing for prompt regulatory action. For example, we identified a compound with high potency and severe adverse effects, leading to its ban. This swift action most likely prevented numerous health incidents that could have resulted from its widespread use."
Tecan’s Spark: Advancing Drug Classification
Designed for real-time kinetic measurements and compatible with various assays, the Spark is well suited for studying receptor activation dynamics. Its sensitivity and automation features streamline the screening process, reducing manual intervention and improving reproducibility across experiments. Henrik highlighted, “The Spark’s ability to perform real-time kinetic measurements and its versatility across assays allowed us to quickly and accurately assess receptor activation over a range of drug concentrations.” The Spark ensured the reliability and accuracy of research findings. Henrik added, “We uphold stringent validation processes and use high-quality equipment like the Spark to ensure precision and consistency in our results.”
The adoption of technologies such as the Spark has expedited the classification of new substances, enabling regulatory agencies to respond quickly to emerging drug threats. This capability is critical for maintaining vigilance in public health with the ever evolving landscape of NPS.
Collaborative Efforts in Drug Classification and Regulation and Broader Implications
The collaboration between Linköping University, PHAS, and NBFM combined the expertize of academia, public health, and forensic science to create a comprehensive approach to drug classification. The aim is to extend this screening method to include other psychoactive substances, such as amphetamines and opioids. This extension is the next step in creating a comprehensive screening tool that can address a wide range of psychoactive substances.
Broader implications for healthcare innovation and regulatory practices are significant. Effective screening and rapid classification of new substances can lead to better-informed public health policies that keep apace of emerging drug threats.
By adopting flexible and adaptive frameworks, investing in advanced screening technologies and fostering collaborations with research institutions, regulatory agencies can respond to new substances in a timely manner. The improvement of regulatory capabilities alongside an increased understanding of emerging trends, regulatory agencies are well positioned to manage the challenges posed by NPS, including synthetic cannabinoids.
For Research Use Only. Not for use in diagnostic procedures.