New Psychoactive Substances (including kratom, synthetic cannabinoids, synthetic opioids, synthetic cathinones, and more).

Related Chapters:
Fentanyl
Entheogens and Psychedelics

Chapter Sections:
Overview
Ketamine
Khat
Kratom
Krokodil
Synthetic Opioids (e.g. Fentanyl)
Synthetic Cathinones (Mephedrone, Methylone)
Phenethylamines
Salvia Divinorum
Synthetic Cannabinoids
Others - New psychoactive substances are being developed at a rapid rate

Page last updated June 10, 2020 by Doug McVay, Editor.

1. Number of New Psychoactive Substances Continues to Grow

"Since around 2008, there has been a dramatic growth in the NPS market as globalisation and new technologies, such as the internet, have allowed them to be produced, sold and supplied on an industrial scale. Between 2009 and 2018, 119 countries and territories reported the emergence of 892 different NPS to UNODC, through the UNODC Early Warning Advisory on NPS (UNODC, 2019b). In Europe, more than 730 NPS have appeared on the drug market since monitoring began in 1997, with around 90 % of these being detected between 2008 and 2018 (EMCDDA, 2019b). The growth in the market has also been reflected in large increases in the number of seizures made by law enforcement agencies, and in reports of severe and fatal overdoses.

"Many NPS are produced and sold openly by chemical and pharmaceutical companies in China. They are imported into Europe, processed into products and sold in shops, on the internet or through the illicit drug markets. To a lesser extent, India is also an important source of some NPS, particularly those sold as medicines (Evans-Brown and Sedefov, 2018). Illicit laboratories in China, India, and Europe also produce some types of NPS."

European Monitoring Centre for Drugs and Drug Addiction and Europol (2019), EU Drug Markets Report 2019,
Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/pu...
http://www.emcdda.europa.eu/sy...

2. Clinical and Public Health Responses to NPS

"Clinical and public health responses to date have focused on acute toxicity from NPS. This attention has grown in previous years with the increased reportings of overdose associated with NPS in several countries. Current examples include rising mortality from benzodiazepine NPS in Scotland (etizolam implicated in 57% of all drugrelated deaths in 2018);123 opioid NPS in North America (fentanyl analogues detected in 20·6% of opioid overdose deaths occurring between July, 2016, and June, 2017, in 10 US states);33 and from synthetic cannabinoids in New Zealand (reportedly in excess of 40 deaths linked to synthetic cannabinoids in 2017–18).124

"In almost all clinical situations of acute toxicity, there is a restricted capacity for rapid confirmation of NPS to inform management: many rapid testing measures are not sensitive to NPS and cannot keep pace with new substances. Current guidance from the Novel Psychoactive Treatment UK Network (NEPTUNE) recommend diagnosis on the basis of clinical assessment and recognition of the clinical toxidrome given that most NPS have similar effects to the more established illicit drugs they are intended to mimic (synthetic cannabinoids being a notable exception).13,14,125 The NEPTUNE guidelines recommend symptomatic and supportive management, particularly in the absence of research on the management of acute toxicity for the varied NPS.13,14,125 The exception is opioid NPS overdose, for which the relative higher potency of some opioid NPS might require changes in clinical management. For example, clinical guidance based on reports from fentanyl analogue overdoses suggest some cases might require higher doses of naloxone, rapid escalation of naloxone dosing, and a longer observation period in a hospital setting than other opioids.125"

Amy Peacock, PhD, Raimondo Bruno, PhD, Natasa Gisev, PhD, Prof Louisa Degenhardt, PhD, Prof Wayne Hall, PhD, Roumen Sedefov, MD, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. The Lancet. Volume 394, Issue 10209, p1668-1684, November 02, 2019. Published:October 23, 2019.
https://www.thelancet.com/...
https://www.ncbi.nlm.nih.gov/...

3. Synthetic Cannabinoid Agonists

"Synthetic cannabinoid receptor agonists (hereafter synthetic cannabinoids) are a chemically diverse group of synthesised compounds that often act on similar receptors to those acted on by Δ-9-tetrahydronnabinol in cannabis. Powders are typically dissolved in solvent, sprayed on inert plant material and then smoked, and are often sold as commercial mixtures (eg, Spice, Kronic).12 Other forms and routes of administration include ingestion of pills or powders, and vaping using solutions containing synthetic cannabinoids. Effects can be similar to those resulting from use of cannabis (eg, euphoria, sedation, and drowsiness), but are typically more severe and sometimes unique from cannabis.13"

Amy Peacock, PhD, Raimondo Bruno, PhD, Natasa Gisev, PhD, Prof Louisa Degenhardt, PhD, Prof Wayne Hall, PhD, Roumen Sedefov, MD, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. The Lancet. Volume 394, Issue 10209, p1668-1684, November 02, 2019. Published:October 23, 2019.
https://www.thelancet.com/...
https://www.ncbi.nlm.nih.gov/...

4. Stimulant New Psychoactive Substances

"Stimulant NPS are drugs with similar effects to amphetamine, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA), which result in increased alertness, energy, confidence, and sociability, and suppression of appetite and fatigue (eg, mephedrone, methylone, α-PVP).14 They are typically in a powder, capsule, tablet, liquid, or crystal form, and are primarily consumed by swallowing or snorting, as well as by injecting."

Amy Peacock, PhD, Raimondo Bruno, PhD, Natasa Gisev, PhD, Prof Louisa Degenhardt, PhD, Prof Wayne Hall, PhD, Roumen Sedefov, MD, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. The Lancet. Volume 394, Issue 10209, p1668-1684, November 02, 2019. Published:October 23, 2019.
https://www.thelancet.com/...
https://www.ncbi.nlm.nih.gov/...

5. Hallucinogen New Psychoactive Substances

"Hallucinogen NPS are a diverse group of substances that alter an individual’s awareness of their surroundings, as well as their thought processes and perception, which can lead to substantial distortions of reality. They can be divided into two main types: dissociatives, which induce euphoria alongside a feeling of weightlessness and detachment from the body; and classic hallucinogens, which produce altered perception,15 causing cognitive and visual disturbances and an altered state of consciousness. Dissociative NPS (eg, methoxetamine) have similar effects to ketamine; psychedelic NPS (eg, 2C drugs, NBOME drugs) have similar effects to lysergic acid diethylamide (LSD) and natural products like psilocybin, but these effects can vary in duration, intensity, and type of experience. Hallucinogen NPS might be a powder, liquid, tablet, or capsule, or on blotter paper, and depending on the drug, are mostly swallowed, snorted, smoked, or injected."

Amy Peacock, PhD, Raimondo Bruno, PhD, Natasa Gisev, PhD, Prof Louisa Degenhardt, PhD, Prof Wayne Hall, PhD, Roumen Sedefov, MD, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. The Lancet. Volume 394, Issue 10209, p1668-1684, November 02, 2019. Published:October 23, 2019.
https://www.thelancet.com/...
https://www.ncbi.nlm.nih.gov/...

6. Depressant New Psychoactive Substances

"Depressant NPS encompass two main types of CNS depressants: opioids, which cause analgesia, euphoria, drowsiness, and sedation (eg, fentanyl analogues); and benzodiazepines, which have sedative, anxiolytic, hypnotic, muscle-relaxant, and anticonvulsant effects (eg, etizolam, phenazepam).15 These NPS can be sold under their own name, but have also been detected as counterfeit prescription medicines (eg, in tablets or capsules), or adulterated with or sold as more established illicit drugs (eg, in powder form).16 They are mostly swallowed, snorted, or injected. Some depressant NPS are prescribed medicines in some countries (the benzodiazepine NPS etizolam is a prescription drug in Japan)17 or have other legitimate uses (the opioid NPS carfentanil is used as a tranquiliser in veterinary contexts and as a selective radiotracer in positron emission tomography).18"

Amy Peacock, PhD, Raimondo Bruno, PhD, Natasa Gisev, PhD, Prof Louisa Degenhardt, PhD, Prof Wayne Hall, PhD, Roumen Sedefov, MD, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. The Lancet. Volume 394, Issue 10209, p1668-1684, November 02, 2019. Published:October 23, 2019.
https://www.thelancet.com/...
https://www.ncbi.nlm.nih.gov/...

7. "New" Psychoactive Substances Are Not Necessarily New

"In the operating guidelines on the early warning system, EMCDDA [European Monitoring Centre on Drugs and Drug Addiction] made it explicit that 'the term ‘new’ did not refer to newly invented, but rather ‘newly misused’' substances as 'most of the drugs in question were first created many years ago.'20 In fact, investigations into the potential use of piperazines as anthelmintic have been reported in scientific literature since the early 1950s.21 Yet they only started to emerge as a health problem in several countries in the decade 2001-2010. Similarly ketamine, which was first developed in the mid-1960s, started to emerge as a health problem in that decade in several countries of East and South-East Asia. Mephedrone was first synthesized in 1929 but was rediscovered only in 2003 and reached the markets towards the end of the decade 2001-2010.22

"NPS also include plant-based substances that have existed for centuries. In the profiles of 'new drugs', EMCDDA lists plant-based substances such as Salvia divinorum and khat. Khat has been known for hundreds of years in the countries around the Horn of Africa and the southern parts of the Arabian peninsula. However, it is considered to be a new substance in a number of European and American countries, as its use was barely known in those regions until one or two decades ago. The same applies to Salvia divinorum, kratom, and various hallucinogenic mushrooms, which are all considered to be NPS.23 Using the definition 'newly misused on the market', the overwhelming number of non-controlled psychoactive substances can be regarded as NPS, as there will always be some countries in which they have not been misused before."

UNODC, World Drug Report 2013 (United Nations publication, Sales No. E.13.XI.6), pp. 62-63.
https://www.unodc.org/unodc/se...

8. New Psychoactive Substances (NPS)

"The creation of new substances to exploit loopholes in drug control legislation has been a problem since the international drug control system was first established. The proliferation of such substances in recent decades was influenced by the work done by Ann and Alexander Shulgin on phenethylamines8 and tryptamines9 in the 1960s and the 1970s. The Shulgins reported over 230 psychoactive compounds that they had synthesized and evaluated for their psychedelic and entactogenic potential. More recently, a number of piperazines, synthetic cathinones and synthetic cannabinoids emerged, which were marketed as 'legal' alternatives to controlled substances."

UNODC, World Drug Report 2013 (United Nations publication, Sales No. E.13.XI.6), p. 60.
https://www.unodc.org/unodc/se...

9. Synthetic Cathinones

"Reflecting their use as legal replacements for cocaine, amphetamine and other controlled stimulants, there were more than 23 000 seizures of synthetic cathinones reported from across Europe in 2016 (Figure 3). These account for almost one-third of the total number of seizures of new substances over the year, and amounted to almost 1.9 tonnes, making synthetic cathinones the most commonly seized new psychoactive substances by quantity in 2016. The EMCDDA is currently monitoring 130 of these substances, including 14 that were reported for the first time in 2016 and 12 during 2017. Synthetic cathinones are generally found in powder form. The five most commonly seized cathinones in 2016 were alpha-PVP, 4-chloromethcathinone, 3-chloromethcathinone, 4-methyl-N,N-dimethylcathinone and 3-methylmethcathinone. The top five cathinones detected in powders were 4 chloromethcathinone (890 kg), 4-chloroethcathinone (247 kg), N-ethylhexedrone (186 kg), 3-methylmethcathinone (126 kg) and mexedrone (50 kg). In recent years, there have been indications of increasing interest in making synthetic cathinones in Europe, including seizures of precursors, equipment and illicit laboratories used to make mephedrone (which is now under international control), as well as 4-chloromethcathinone and 3-chloromethcathinone."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/pu...
http://www.emcdda.europa.eu/sy...

10. New Benzodiazepines

"Reflecting consumer demand, the market in new benzodiazepines appears to have grown over the past few years. The EMCDDA is currently monitoring 23 of these substances, including six that were reported for the first time in 2016 and three during 2017. While the overall number of seizures reported by law enforcement during 2016 decreased compared with 2015, the quantity reported increased. More than half a million tablets containing new benzodiazepines such as diclazepam, etizolam, flubromazolam, flunitrazolam and fonazepam were reported during 2016 — which was about 70 % more than in 2015. Some of these new benzodiazepines were sold as tablets, capsules or powders under their own names. In other cases, they were used to make fake versions of commonly prescribed benzodiazepine medicines, such as diazepam and alprazolam, and sold directly on the illicit drug market."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/pu...
http://www.emcdda.europa.eu/sy...

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