The age of novel psychoactive substances

Mar 9, 2023 | Blogs, Forensic, Toxicology | 0 comments

Read time: 10 min

Novel psychoactive substances (NPS) are compounds designed to mimic existing recreational drugs. The emergence of NPS has changed the landscape of the synthetic drug market. While previously the market had a limited number of compounds belonging to a few chemical groups, with NPS it now has hundreds of compounds. The European Monitoring Center for Drugs and Drug Addiction is currently monitoring 730 substances, with more being identified each year.

In the past, NPS were called “legal highs” because they were not covered by anti-drug laws. Manufacturers achieved this by tweaking the pharmacological structures of existing compounds to create new substances. To tackle this problem, and make “legal highs” illegal, different countries passed new laws to create a blanket ban on NPS. For example, in the UK and Ireland, the 2016 Psychoactive Substances Act makes it an offense to produce or supply—but not possess, unless an individual is in prison—current and future NPS.

In the US, the Synthetic Drug Abuse Prevention Act of 2012 bans synthetic cannabinoids, synthetic cathinones and hallucinogenic drugs. This law classifies these drugs as Schedule 1 substances under the Controlled Substance Act, which are defined as drugs that have a high potential for abuse, have no accepted medical use in the US and are not classed as safe. Despite these laws, the supply, use and possession of NPS has not decreased. In fact, since the Synthetic Drug Abuse Prevention Act went into effect, the strength and price of NPS have increased.

The most prevalent NPS can be grouped into four categories based on their similarity to established medical and recreational drugs—benzodiazepines, opioids, stimulants and hallucinogens and synthetic cannabinoids—with stimulants and cannabinoids being the most commonly used.1,2 Here, we take a closer look at each of these four categories of NPS with additional insight from Alex Krotuslki, research scientist at the Center for Forensic Science Research and Education and program manager for their NPS Discovery program.

NPS benzodiazepines

Benzodiazepines are one of the most widely prescribed groups of medicines in the world. They are central nervous system depressant drugs, prescribed for anxiety, epilepsy, insomnia and alcohol withdrawal.

Novel designer benzodiazepines (DBZDs) have emerged on the recreational drug market, and their misuse and abuse have become an increasing problem in many countries. The benzodiazepine class of NPS includes pharmaceutical drug candidates that were never approved for medical use, compounds that were synthesized by a simple structural modification of a registered drug and some active metabolites of registered benzodiazepines.

NPS opioids

Synthetic opioids are substances synthesized in a laboratory and that act on the same targets in the brain as natural opioids (such as morphine, heroin and codeine) to produce analgesic (pain relief) effects. Some synthetic opioids, such as fentanyl and methadone, have been approved for medical use.

Many illicitly produced synthetic opioids, such as fentanyl analogs and nitazenes, are more potent than morphine and heroin and therefore have the potential to result in a fatal overdose.

NPS stimulants and hallucinogens

Forensic laboratories usually lump these two NPS categories together, since the user population sometimes overlaps, and some of these drugs can have both stimulant and hallucinogenic properties, such as ketamine.

NPS stimulants mimic the effects of traditional psycho-stimulants—such as 3,4 methylenedioxymethamphetamine (MDMA), cocaine and amphetamines—producing a sense of euphoria and well-being by increasing the synaptic levels of serotonin, dopamine and noradrenaline. NPS stimulants include synthetic cathinones, or SCs (such as mephedrone), substituted phenylethylamines (known as 2C drugs) and piperazines (such as benzylpiperazine). While stimulants are typically sold in a powder or pill format, SCs are often sold under the disguise of plant food or bath salts (hence the street name “bath salts”). SCs are normally snorted or ingested orally—for example, wrapped in cigarette paper (known as “bombing”) or dissolved in water (called “whizzy water”).1,2,3

NPS hallucinogens mimic the effects of traditional hallucinogens, such as lysergic acid diethylamide (LSD) and psilocybin (known as “magic mushrooms”). Despite their name, instead of hallucinations, they produce a range of “psychedelic effects,” such as perceptual alterations and quasi-mystical experiences. These effects can be categorized under oceanic boundlessness (where the user experiences positive emotions ranging from heightened mood to sublime happiness and serenity or grandiosity) and anxious ego-dissolution (where the user experiences thought disorder and loss of autonomy and self-control associated with arousal, anxiety and paranoid ideations).1 The most common hallucinogens are derived from phenethylamine, which is synthetically engineered to mimic the effects of natural hallucinogens. NPS hallucinogens include 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe, three NPS hallucinogens belonging to the NBOMes compound class. These substances are often sold in the form of powders, liquid solutions, laced on edible items, and soaked onto blotter paper.

Dissociatives are a type of hallucinogen that distort visual and auditory perceptions, causing the perception of an absence of time, weightlessness and disconnection from the physical body. All of these effects lead to detachment and potent psychedelic experiences. Traditional dissociatives include phencyclidine (PCP) and ketamine. They can be inhaled, swallowed or injected and have effects that can range from milder with ketamine to stronger with PCP.1,3 NPS dissociatives include ketamine, PCP, methoxetamine DXM and diphenidine, and have been encountered as a white, off-white, beige or yellow powder but can also be found in a pill form, liquid solution and soaked onto blotter paper.

NPS synthetic cannabinoids

NPS variants of cannabinoids are termed synthetic cannabinoid receptor agonists (SCRAs). The common street names for SCRAs include “Spice” and “K2,” and they are often packaged into foil sachets and sold as incense. SCRAs are usually solids or oils sprayed onto herbal mixtures that are smoked. Liquid SCRAs can be used in electronic cigarettes and vaporizers.1,2,3

NPS availability, trends and concerns

The dark net uses custom software and hidden networks superimposed onto the architecture of the internet. Since it has a low risk of detection, the dark net can be used for the sale of restricted goods, making it an “attractive” platform for obtaining NPS.4 According to a 2016 Global Drug Survey (GDS), online purchases of NPS are increasing,7 and according to the last World Drug Report in 2018, synthetic cannabinoids and SCs represent the largest class of NPS.5 This is a problem, as synthetic cannabinoids are more likely to lead to emergency medical treatment than any other NPS.7

In summary, NPS are on the rise globally, and so are incidences of intoxication and death. The major challenge with NPS is the lack of identification tools, which exacerbates the difficulties medical practitioners face when determining the best treatment route for patients. This lack of tools also makes it difficult for forensic staff to identify illegal substances, leading to a lack of prosecution that can in turn encourage an increase in NPS drug use.


  1. Global Smart Update. 19. 1-12. (2018).
  2. K. Tracy et al. BMJ. 356. 1-7. (2017).
  3. Dignam. BJA Educ. 17 (5). 172-177 (2017).
  4. Europol. 1-88. (2017).
  5. World Drug Report (2018)

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