Combatting the rising threat of new psychoactive substances

Earlier this month, the Ministry of Home Affairs announced that it is reviewing laws to combat the rising threat of new psychoactive substances (NPS) in Singapore.

The amendments will allow the Central Narcotics Bureau (CNB) to take swifter action against abusers and traffickers of these substances that have potential to produce a psychoactive effect.

For thousands of years, humans have been using cannabis for medicinal purposes, as well as misusing it for recreational purposes.

The chemical responsible for the mind-altering effects of naturally-cultivated cannabis is tetrahydrocannabinol (THC), and abuse of it can lead to adverse physical or psychological effects.

A United Nations (UN) commission voted on Dec 2, 2020 to remove cannabis from the category of the world’s most dangerous drugs for medicinal purposes.

The United States and European nations were among those who voted in favour, while other countries including Singapore opposed the reclassification.

Singapore’s strong stance against the legalisation of cannabis is substantiated by scientific evidence on its adverse effects and abuse potential. Beyond cannabis, and lesser known to the public, are these emerging NPS.

By definition, NPS are drugs of abuse that are not controlled by the 1961 UN Convention on Narcotic Drugs or the 1971 UN Convention on Psychotropic Substances, but which might pose a public health threat.

Driven by scientific curiosity and a worthy intention to develop new medicines, chemists synthesised variations of naturally-isolated active chemicals such as THC.

The publication of such scientific information inadvertently became a treasure trove for ill-intended entrepreneurs to develop potent NPS for the clandestine markets.

The real-life zombie apocalypse in New York City reported in 2016 was due to the abuse of one such NPS, known as synthetic cannabinoid, which was estimated to be 85 times more potent than THC.

The glut of NPS in the past decade poses unprecedented challenges for drug policy and public health globally. Underpinning these challenges are four key elements.

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  Elusive detection
  NPS possess novel and diverse chemical structures allowing them to evade standard forensic tests. Some NPS also undergo rapid metabolism in the body and the parent drugs could not be detectable in the blood or urine after a short period of time. Consequently, the confirmation of the ingestion of NPS among abusers becomes arduous for law enforcers.

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  Ambiguous legal status
  The chemical structures of NPS differ from their predecessors (which include hallucinogens, stimulants, depressants, and euphoriants) that are classified in restrictive drug schedules of controlled drugs and in international conventions. Vicious entrepreneurs are unsurprisingly incentivised to mine scientific journals, modify the structures of restricted drugs, and produce chemically diverse NPS that fall into legal grey zones.

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  Furtive online marketing
  The internet is easily exploitable for the marketing and distribution of the NPS globally. The European Union-funded Psychonaut Web Mapping Project monitored more than 200 discussion forums, social media, online shops, websites and other internet resources, and recorded 400 NPS over two years. Most internet sites are impervious to legal sanctions as the NPS are unregulated. Guileful packaging and labelling further obscure the authentic identity of NPS and promotes their use globally. In Singapore, CNB reported the arrest of 414 NPS abusers in 2019 as compared to just one case in 2017.

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  Undesirable medical consequences
  Expectedly, it is challenging to predict the short- and long-term adverse effects of the NPS. A recent review article published in the Mental Health Clinician journal reports a range of severe blood, brain, heart, kidney and psychiatric toxicities and fatality associated with the use of synthetic cannabinoids. Drug abusers intoxicated with NPS present a significant burden to international healthcare systems.

Notwithstanding these challenges, there are feasible solutions to consider in tackling these problems.

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  Biomarkers of NPS
  As NPS are metabolised in the liver to form metabolites which are subsequently excreted by the kidney, wet laboratory and physiologically-based modelling experiments can be performed to investigate and estimate how long the parent NPS and their major metabolites could circulate in the body. In collaboration with the Health Sciences Authority of Singapore (HSA), my research team at the National University of Singapore has adopted these scientific models. We reported in the Archives of Toxicology journal on the urinary biomarkers to be monitored for studying the ingestion of two emerging NPS in Singapore in November 2020. These biomarkers are currently being used by the HSA in their test panel to screen for consumption of both NPS in urine samples.

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  Scheduling of NPS
  In an effort to constrain the explosion of NPS, a Synthetic Drug Control Act of 2015 was introduced in the United States Congress where more than 200 synthetic substances were added to the most restrictive Schedule I. Internationally, the World Health Organization (WHO) separately, and in conjunction with other UN agencies, conducts similar surveillance and recommends updates on scheduling. In Singapore, apart from controlling some of the NPS individually, generic listing of a number of NPS-related core chemical structures has been adopted in the legislation as a way to control the wide range of these NPS derivatives, even when they are further modified chemically. This implies that the trafficking, possession and consumption of such NPS derivatives becomes an offence that attracts heavy punishments in Singapore.

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  Harnessing Internet
  The internet is the driver of NPS, but it can also be leveraged to manage its impact. The Recreational Drugs European Network (ReDNet) project is the first Europe-wide prevention programme designed to enhance the level of information available to young people and professionals on the potential health risks associated with NPS via social media technology-based intervention. In the United States, a newly established National Drug Early Warning System uses state-of-the-art methodologies to track emerging drug trends and disseminate information to the public. Such globally shared information should also be integrated in the school and community education programmes to further step up the prevention efforts.  

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  Interdisciplinary research
  A challenge of these prevention campaigns is the lack of scientific evidence to document the potential medical consequences of NPS to users. One solution is to identify the most problematic NPS based on global trends, and prioritise biological screening of these NPS to understand their potential adverse effects. Combining this information with our understanding of how the body handles the NPS, scientists may predict the medical consequences in abusers due to their genetic make-up, concomitant medications or alcohol consumption and underlying disease conditions. This may in turn help the clinicians to better manage medical emergencies associated with the use of NPS.

In conclusion, the emergence of NPS is challenging but there are feasible solutions to address the problems. International collaboration and interdisciplinary research are needed to prevent the ill-informed use of NPS and manage their unforeseen toxicities. Ultimately, research-guided prevention education will fortify societies against this tsunami.

ABOUT THE AUTHOR:

Professor Eric Chan is a pharmaceutical scientist with the department of pharmacy at the National University of Singapore.