New Psychoactive Substances (NPS): How Can We Monitor Drugs That Constantly Change?

Today, researchers, healthcare systems, and public safety agencies worldwide face a major challenge: the rapid growth of so-called new psychoactive substances (NPS). NPS are newly emerging drugs created through modifications to existing chemical structures, and new compounds appear almost every week. New chemical structures often mean unknown toxic effects, as well as difficulties in identifying and legally controlling these substances. How can science keep pace with the relentless emergence of these drugs? A project led by Prof. Dr. José Luiz da Costa from the University of Campinas (Unicamp), in partnership with the São Paulo State Superintendency of Scientific Police (SPTC), aims to provide a solution.

In this article, we interviewed Dr. Maria Paula de Oliveira Valadares, a forensic scientist at the SPTC and the public manager responsible for coordinating the project on behalf of both the SPTC and the São Paulo State Secretariat of Public Security.

Between the Laboratory and Criminal Investigation

Dr. José Luiz da Costa is an Associate Professor at the School of Pharmaceutical Sciences of Unicamp and an advisor in the Graduate Program in Pharmacology. His academic background includes a degree in Biochemical Pharmacy from the Federal University of Alfenas, a Master’s degree in Toxicology and Toxicological Analysis from the University of São Paulo (USP), and a Ph.D. in Analytical Chemistry, also from USP. In addition, he completed postdoctoral training at Unicamp and at the National Institute on Drug Abuse (NIH, USA).

Prof. José Luiz also serves as coordinator of the Campinas Toxicological Information and Assistance Center (CIATox-Campinas). This specialized service, affiliated with Unicamp’s School of Medical Sciences (FCM), integrates public assistance, education, and research. Established in 1982 and linked to the University Hospital, CIATox-Campinas provides support for cases of poisoning involving medications, drugs, chemicals, or venomous animals.

CIATox-Campinas offers in-person, laboratory, and telephone support. Healthcare professionals and members of the public can contact the center at +55 (19) 3521-7555 and receive 24-hour assistance for poisoning cases.

Today, Prof. José Luiz is recognized as one of Brazil’s leading experts in analytical and forensic toxicology. This scientific field focuses on identifying and measuring toxic substances (such as drugs and poisons) in the human body or in seized materials. It plays a critical role in understanding poisoning cases, determining causes of death, and supporting criminal investigations.

It is no coincidence that Prof. José Luiz bridges science and forensic applications. Before becoming a professor at Unicamp, he worked as a forensic scientist for the São Paulo State Superintendency of Scientific Police for more than a decade.

Prof. José Luiz leads research focused on drugs of abuse, with particular expertise in advanced analytical methods and the monitoring of emerging substances. In other words, he investigates how new drugs of abuse emerge and how they can be identified. This is precisely the area addressed by the project discussed in this article.

What Are Drugs of Abuse?

Drugs of abuse are psychoactive substances used to produce pleasurable sensations or alter mental states. They are called psychoactive because they act on the brain, changing how it functions and influencing the way people think, feel, or perceive the world. Different drugs produce different effects, including relaxation, euphoria, drowsiness, and even hallucinations.

Drugs of abuse may be illegal, such as cocaine, or legal, such as alcohol and certain medications when misused. They can lead to addiction and cause problems in personal, social, and professional life. They may also result in a wide range of health consequences, including neuropsychiatric disorders and overdose.

According to the III National Survey on Drug Use by the Brazilian Population (2017), the most commonly used illicit psychoactive substances in Brazil are cannabis (7.7%), cocaine (3.1%), solvents (2.8%), crack and related substances (0.9%), LSD (0.8%), and MDMA (0.7%).

MDMA (3,4-methylenedioxymethamphetamine), commonly known as ecstasy, was the first new psychoactive substance (NPS) identified in Brazil, in 1990. MDMA is a synthetic drug, meaning it is artificially produced in a laboratory through chemical reactions, unlike cannabis (a plant) or cocaine (which is also plant-derived). Today, MDMA remains the most widely consumed synthetic drug of abuse in Brazil.

Following MDMA, other NPS emerged during the 2000s, including 2,5-dimethoxy-4-bromoamphetamine (DOB) and meta-chlorophenylpiperazine (mCPP). More recently, an increasing number of NPS have appeared, including the so-called “K drugs” (synthetic cannabinoids).

To put this into perspective, the Brazilian Federal Police identified 10 NPS for the first time in 2017 and 16 in 2018, a 60% increase in just one year. On a global scale, the situation is even more concerning: between 2009 and 2021, a total of 1,124 NPS were identified, corresponding to the emergence of more than one new substance every week.

But What Exactly Are New Psychoactive Substances (NPS)?

According to the United Nations Office on Drugs and Crime (UNODC), NPS are substances of abuse that are not controlled under either the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances. These international treaties establish rules for controlling the production, use, and distribution of drugs worldwide, aiming to protect public health and combat drug trafficking.

The creation of NPS is often intended to circumvent these conventions and national legislation. Because they are newly developed substances, specific laws regulating their use and trafficking frequently do not yet exist. As a result, they may appear to be legal and, in some cases, can be sold openly on the internet. They are also often less expensive than traditional illicit drugs.

NPS are generally produced through small modifications to the chemical structures of already known drugs. For example, the “K drugs” mentioned earlier are synthetic cannabinoids designed in laboratories to mimic the effects of cannabis on the brain. They can be developed by modifying the structure of THC (tetrahydrocannabinol), the main psychoactive component of cannabis.

NSP / NPS — Figurative illustration of the THC molecule (tetrahydrocannabinol, a cannabinoid) undergoing structural modifications to generate a synthetic cannabinoid (a New Psychoactive Substance, NPS).

Because NPS are modified substances, relatively little is known about their effects on the human body. In many cases, they are far more potent than traditional drugs or may produce entirely unpredictable effects. This leads to intoxication cases that challenge healthcare professionals and pose serious risks to public health.

Cases of NPS intoxication can rapidly progress to severe conditions. Common complications include neurological crises, cardiovascular problems, psychiatric disorders, and even death. Because information about these substances is limited, diagnosis and treatment become extremely difficult in emergency settings, placing an additional burden on healthcare systems.

CIATox-Campinas itself has observed a rise in cases involving synthetic cannabinoid intoxication. Between 2016 and the end of 2022, only two cases were identified. However, during the first five months of 2023 alone, ten cases were recorded.

A Race Against Time

The constantly changing chemical structures of NPS make not only the diagnosis and treatment of intoxication cases more difficult, but also the chemical identification of these substances. Since their structures are often unknown, detecting NPS through analytical methods becomes particularly challenging.

Small modifications in a chemical structure are enough to create a “new” substance. The enormous diversity of these structures and the relentless emergence of new NPS are difficult to keep up with. In many cases, there are no records of these molecules in existing databases. Without reference standards, laboratories lack suitable analytical methods to detect them.

It is like being asked to identify the ingredients in a dish when one of them is a spice you have never tasted before. Consider belacan, a fermented shrimp paste commonly used in Malaysian, Singaporean, and Indonesian cuisine. Most people (myself included) would have no idea what belacan tastes like and would never taste a dish and say, “Oh, they definitely added belacan to this fish.”

Just as we need to know the taste of a spice to recognize it, analytical methods require prior knowledge of a molecule in order to identify it.

Forensic analytical toxicology must detect NPS both in seized materials and in the human body. Synthetic cannabinoids, for example, are often dissolved in solvents and sprayed onto dried plant materials such as herbs, paper, or even tobacco. When these materials are seized, investigators must determine whether an NPS is present.

The challenge becomes even greater when detecting NPS in human samples. These substances are often present at extremely low concentrations in blood, urine, and other biological matrices. As a result, highly sensitive and sophisticated analytical techniques are required, methods that are frequently expensive, difficult to access, and dependent on highly trained professionals.

This scenario exposes a major weakness in public health and public safety systems: the lack of a structured and continuous mechanism capable of tracking the emergence of NPS in real time.

From the Laboratory to Public Policy: The NSP-Monitor Proposal

The NSP-Monitor project was created precisely to address this gap. Led by Prof. José Luiz, the initiative is carried out in partnership with the São Paulo State Superintendency of Scientific Police (SPTC), with forensic scientist Dr. Maria Paula de Oliveira Valadares serving as the public manager responsible for the project.

The project is entitled “Monitoring New Psychoactive Substances in the State of São Paulo: Integrated Actions for Public Policies in Public Safety and Public Health Regarding Synthetic Drugs (NSP-Monitor Project)”. It recently received funding from the São Paulo Research Foundation (FAPESP) through its Public Policy Research Program (grant no. 24/15262-5).

The proposal is to integrate multiple sources of information into a single system. Forensic reports from the Scientific Police, clinical data from CIATox, and seizure records will be combined to create a comprehensive NPS database. This database will enable researchers and policymakers to cross-reference information on identified substances, geographic locations, periods of higher incidence, and patterns of intoxication.

In addition, an interactive dashboard will be developed. This platform will provide public access to non-sensitive criminal investigation data, increasing transparency and facilitating the use of information by both decision-makers and society. Users will be able to compare data across regions, time periods, and other relevant parameters.

Initially, the NSP-Monitor project will focus on the Greater São Paulo region, Campinas, and Americana. These areas were selected because of their high population density and the availability of data from healthcare services and forensic institutions. Once the system has been established and validated, the knowledge generated may be expanded to other regions of Brazil.

Science in Service of Public Safety

The São Paulo State Superintendency of Scientific Police (SPTC), one of the project’s institutional partners, is represented by Dr. Maria Paula de Oliveira Valadares as the public manager responsible for its implementation. Dr. Valadares holds bachelor’s degrees in Chemistry and Law, a Ph.D. in Biotechnology, and a specialization in Digital Law and Technological Innovation. She has worked as a forensic scientist since 2006.

Currently, Dr. Valadares serves as one of the coordinators of the Analysis and Planning Division within the São Paulo State Secretariat of Public Security, the department responsible for producing official statistics and planning public security policies. Her work involves data analysis and the development of evidence-based strategies to support governmental decision-making.

With expertise spanning science, technological innovation, forensic investigation, and public administration, Dr. Valadares plays a key role in connecting the scientific outcomes of NSP-Monitor with their practical application in public health and public safety policies.

Dr. Valadares explains her role in the project: “My role is to ensure strategic alignment between Unicamp’s scientific research and the real needs of public security, acting as an institutional facilitator. I use my experience in public policy formulation and implementation to guide the development of policies based on the evidence that the system will generate.”

She also highlights the importance of the partnership with the SPTC: “The SPTC is the largest scientific police institution in Latin America. It is the operational heart of the data. The Narcotics Examination Unit and the Forensic Toxicology Unit, together with the regional Criminalistics Units, will provide analyses of controlled substances and toxicological examinations, both antemortem and postmortem, which will continuously feed the project’s database.”

“Antemortem” and “postmortem” are Latin terms widely used in medicine and forensic science. Antemortem examinations use samples collected before a person’s death, such as blood, urine, or other materials obtained during medical care. Postmortem samples are collected after death, usually by forensic pathologists.

Dr. Valadares also describes the role of the São Paulo State Secretariat of Public Security (SSP): “The SSP operates at the macro and strategic level, supporting institutional coordination. It is also represented by associate researcher Rodrigo Garcia Vilardi and will be the primary beneficiary of the Business Intelligence tools developed by the project, using geographic and temporal indicators to plan police intelligence and preventive policing actions.”

In practice, this means that the data generated by the project will be transformed into tools capable of identifying where and when specific drugs are circulating. With this information, public safety agencies will be able to detect trends, anticipate risks, and plan investigation and prevention strategies more effectively.

Dr. Valadares also emphasized that NSP-Monitor will be integrated into the Paulista Wall Program (Programa Muralha Paulista). This initiative of the São Paulo State Government uses cameras, license plate readers, and intelligence systems to integrate public security data. The program aims to support crime prevention and investigation through real-time monitoring and information analysis.

For Dr. Valadares, the main significance of NSP-Monitor lies in enabling evidence-based decision-making: “This project breaks the isolation of laboratories. It gives public managers the power to predict scenarios and direct police and healthcare resources precisely to the regions most affected.”

She adds: “The project will generate rapid alerts regarding the emergence of dangerous new toxic substances, such as ‘K drugs’ and new synthetic opioids. In this way, it simultaneously equips law enforcement agencies for investigation and enforcement and emergency healthcare teams for improved diagnosis and lifesaving interventions.”

The Technology Behind NPS Identification

One of the main challenges of the NSP-Monitor project is developing ways to identify NPS. The analytical technique most commonly used today for their detection is liquid chromatography coupled with mass spectrometry. I know the name sounds complicated, but the basic idea is simpler than it seems.

Imagine you have a mixture containing several “invisible ingredients,” such as a shampoo. If you look at the label, you will find a long list of ingredients with complex names that most of us have never heard of and do not know the function of. A sample suspected of containing NPS is quite similar, whether it is seized material or a patient’s blood sample.

Liquid chromatography works like a highly sophisticated sieve. It separates all these substances and organizes them as if they were standing in a line. Each substance is then analyzed by mass spectrometry, which acts as an extremely precise detector capable of “weighing” and identifying each molecule. It is almost as if a chemical ID card were generated. Just as every person has a unique identity document, every molecule has its own unique chemical signature that allows it to be recognized accurately.

Analytical methods used to detect NPS can be divided into targeted and non-targeted approaches. Targeted methods are appropriate when the substances of interest are already known. For unknown NPS, however, non-targeted methods are preferred because they allow for broader screening without requiring prior information.

For this reason, the researchers will focus on developing and validating non-targeted methods for NPS detection. These methods are more expensive, more complex, and require greater technical expertise. However, once an NPS has been detected, information about its chemical characteristics can be deposited into databases. This enables future identification using targeted methods, which are faster, simpler, and less expensive.

Another important aspect of the project is the development of environmentally sustainable methods aligned with the concept of green analytical toxicology. These new approaches aim to use smaller sample volumes and fewer chemical reagents while generating less waste. Ultimately, this strategy seeks to establish methodological references for public laboratories, enabling them to adopt analytical techniques that are more affordable, sustainable, and effective without compromising the reliability of results.

The Research Conducted by the Group

This is not Prof. José Luiz’s first effort in this field. Since 2016, his research team has been investigating the NPS phenomenon in Brazil by analyzing biological samples, seized materials, and even fluids collected at public events. These studies have already demonstrated, for example, the remarkable variability in the composition of synthetic drugs sold throughout the country.

Book and scientific articles published by Prof. José Luiz and his research group.

A recent example is a study published in the journal Drug Testing and Analysis. The publication’s first author was Ph.D. candidate M.Sc. Alexandre Barcia de Godoi. The study reported, for the first time, the identification of a novel synthetic cannabinoid called MDMB-5′Br-PINACA in plant material seized in the countryside of São Paulo State. The paper describes the extensive effort and intricate methodology required to decipher the chemical structure of a new psychoactive substance.

The findings also revealed an even more complex and alarming scenario: the seized samples contained mixtures of different synthetic drugs, including cannabinoids, benzodiazepines, and even opioids.

Another recent study, highlighting how the group contributes both to forensic investigations and public health monitoring, was published in the Journal of Analytical Toxicology. The paper’s first author is Ph.D. candidate M.Sc. Karla Aparecida de Oliveira Souza and presents the development and validation of a method for detecting benzodiazepines in postmortem blood samples.

The method demonstrated high accuracy and was capable of detecting these substances at very low concentrations. An additional advantage is that the approach is more environmentally sustainable than many existing techniques. Karla’s doctoral research also involves the development of methods for detecting NPS in postmortem samples.

As mentioned earlier, detecting NPS is not the only challenge. Understanding their toxic effects on the body is equally important. For this reason, the group also conducts experimental studies aimed at understanding how these substances act in the organism and what kinds of damage they may cause. Examples include the undergraduate research project of Laura de Souza Borbi and the doctoral research of Leonardo Costalonga Rodrigues, both funded by FAPESP.

One of the main experimental models used in these studies is the zebrafish (Danio rerio). This organism is widely employed in scientific research because it allows rapid and controlled observation of toxic effects, behavioral alterations, and drug metabolism processes.

In these experiments, researchers evaluate everything from toxicity in embryos and larvae to behavioral changes such as altered locomotion, anxiety, and social interaction following exposure to NPS. They also investigate how the organism transforms these substances (biotransformation) and identify the resulting compounds (metabolites), which may serve as important biomarkers in toxicological testing.

A recent publication in Discover Toxicology, with Ph.D. candidate Leonardo as first author, investigated the effects of the synthetic cannabinoids ADB-INACA and CHO-4′Me-5′Br-FUBOXPYRA in zebrafish. One particularly interesting aspect of the study was the evaluation of self-administration behavior, a method used to assess a substance’s potential to cause dependence.

In simple terms, this type of experiment evaluates whether the animal actively “seeks” the drug, that is, whether it performs an action in order to receive the substance. In the case of the NPS evaluated in this study, the results showed that they did not induce drug-seeking behavior in adult fish, unlike substances known to produce dependence.

In addition to the scientific articles, the book New Psychoactive Substances (“Novas Substâncias Psicoativas”) was recently published and edited by Professors José Luiz da Costa and Mauricio Yonamine (USP). The volume brings together experts to discuss the challenges related to the identification, toxicity, monitoring, and public health and public safety impacts of these substances, making it an important reference in the field.

In a scenario where drugs are constantly changing, the response must be equally dynamic and evidence-based. For this reason, NSP-Monitor aims to go beyond scientific production by working in close collaboration with both public health and public safety sectors. In the future, the project may serve as a model for the entire country, demonstrating how the integration of science, technology, and public administration can transform data into action.

The research highlighted in this article was supported by FAPESP (grant numbers 21/04768-7, 22/00037-0, 23/07323-1, 24/08365-2, 24/02868-2, 24/10492-2, 24/15262-5, and 25/00898-4), CNPq (grant numbers 315640/2021-9, 309124/2025-5, 403396/2024-7, and INCT-SP 406958/2022-0), and CAPES (INSPEQT 2.0 project, grant number 2/2024).

This article was produced with the support of the São Paulo Research Foundation (FAPESP), Brazil. Grant No. 25/17158-3. The opinions, hypotheses, conclusions, and recommendations expressed herein are those of the author(s) and do not necessarily reflect the views of FAPESP.

Written by:

Mia Schezaro Ramos
Pharmacist. Ph.D. in Pharmacology. Science journalist, illustrator, trans, Nintendo enthusiast, K-pop fan, and dependent on physical exercise to stay sane.