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During the last decade, there has been an increase in the availability and use of novel psychoactive substances (NPS), also known as "legal highs," across the world. They include a wide range of products, from natural plant-originated substances to synthetic compounds sold online and from high street ...

During the last decade, there has been an increase in the availability and use of novel psychoactive substances (NPS), also known as "legal highs," across the world. They include a wide range of products, from natural plant-originated substances to synthetic compounds sold online and from high street retailers. "Legal highs" mimic psychoactive effects of illicit drugs of abuse. However, they are claimed to consist of compounds that are legal to sell, possess, and use, often labeled as "not for human consumption" to circumvent drug abuse legislation. Based on the spectrum of their actions on cognitive processes, mood, and behavior, synthetic drugs or "legal highs" can be classified into four basis categories: amphetamine- and ecstasy-like stimulants, synthetic cannabinoids (SCs), hallucinogenic/dissociative, and opioid-like compounds. NPS may, however exhibit a combination of these actions due to their designed chemical structure. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these substances. However, the number of intoxicated people presenting with emergencies is constantly increasing, providing evidence that negative health and social consequences may seriously affect recreational and chronic users. Although the prevalence and pattern of NPS use differ between various countries, this Research Topic will focus on the most popular categories of synthetic cathinones and SCs.
Synthetic cathinones popularly known as "bath salts" are designer drugs of the phenethylamine class, structurally and pharmacologically similar to amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cathinone and other related substances. New analogues, legal at least until formally banned, are introduced almost daily. The United Nations estimates nearly 250 new drug analogues are produced per year. Various combinations of these drugs are sold under the name of "bath salts". They can be ingested by any route and some appear capable of causing great harm mostly behavioral. Little is known about the pathology or clinical toxicology of these drugs but their molecular mechanism of action seems to be identical with that of amphetamines.
Synthetic cannabis products are smoke-able herbal mixtures that are being sold under different brand names in Europe such as ‘Spice’ since 2006 (European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), 2009). Although advertised as an ‘exotic incense blend which releases a rich aroma’ and ‘not for human consumption’, when smoked, ‘Spice’ products have been reported by some users to have effects similar to those of cannabis. There are also highly potent synthetic cannabinoids such as AM2201 that are 40 times more potent than cannabis. Although seem innocent, these substances are highly potent and even short or occasional use can result in side effects such as insomnia, memory impairment, headaches, dizziness, and delusions. The emergence of synthetic cannabinoid drugs is a significant new development in the field of so-called ‘designer drugs’. There are more than 100 known compounds with cannabinoid receptor activity and more of such substances from different chemical groups are expected (with direct or indirect stimulation of CB1 receptors). So far, the ‘Spice’ and ‘Spice’-like preparations in Europe have been found to contain at least nine new substances from three chemically distinct groups of synthetic cannabinoids (JWH, CP and HU), plus a fatty acid amide with cannabinoid-like activity (oleamide).
Among the new hallucinogenic/dissociative drugs, a number of arylcyclohexylamines like methoxetamine (MXE), 3-MeO-PCP, diphenidine and 2-methoxydiphenidine (2-MXP) have attracted great attention and represent a rapidly evolving class of molecules available on the global illicit drug market as a substitute for ketamine and other controlled substances. They are thought to act primarily via antagonism of the N-methyl-D-aspartate (NMDA) receptor and are responsible of an increasing number of acute toxicity cases. New potent synthetic opioids, such as ocfentanil, acrylfentanyl and MT-45, are also achieving wide popularity among NPS users, but often with fatal consequences. Similarly to synthetic cathinones and cannabinoids, the newest ketamine-like substances and synthetic opioids represent a challenge to policymakers, clinicians, and forensic investigators charged with their identification.
The main goal of the present Research Topic is to explore and review studies on pharmacological, epidemiological, detection and health consequences of the use of NPS. Case reports and clinical studies on NPS intoxications will also be included, along with emerging evidence from basic research investigating the effects of NPS on the brain's pharmacology and function. Mental health risk factors and underlying brain mechanisms will be examined, with particular emphasis given to the role of NPS in modulating brain neurotransmission and behavior.

Keywords: Novel Psychoactive Substances, Synthetic cathinones, Synthetic cannabinoids, hallucinogenic/dissociative drugs

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